Pharmaceuticals and Urine

《中国药典》2020 年版四部通则英文

《我国药典》2020年版四部通则英文1. IntroductionChina Pharmacopoeia is a national standard for the quality control of drugs and medicinal materials in China. It plays a crucial role in ensuring the safety and efficacy of pharmaceutical products and promoting the development of traditional Chinese medicine (TCM). The "China Pharmacopoeia 2020 Edition" consists of four parts, including the General Principles, Traditional Chinese Medicine, Chemical Drugs, and Biological Products. This article will focus on the English translation of the General Principles, which serves as the foundation and standardization of the entire pharmacopoeia.2. History and SignificanceThe General Principles of "China Pharmacopoeia" provide essential guidelines for the identification, quality control, and standardization of drugs and medicinal materials. It covers general requirements, quality standards, testing methods, and labeling requirements for pharmaceutical products. The General Principles 本人m to ensure the safety, effectiveness, and consistency of drugs, which is critical for public health and the development of the pharmaceutical industry. The Englishtranslation of the General Principles is significant for internationalmunication, collaboration, and the globalization of TCM.3. Structure and ContentThe General Principles of "China Pharmacopoeia" consist of several sections, including General Rules, General Tests, and Reagents, Dosage Forms, and Quality Standards. The General Rules section outlines the basic requirements for the quality control of drugs and medicinal materials, covering aspects such as identity, purity, andposition. The General Tests and Reagents section provides det本人led testing methods and reference standards for the analysis of pharmaceutical products. The Dosage Forms section specifies the quality standards and testing methods for various dosage forms, such as tablets, capsules, and injections. The Quality Standards section sets specific requirements for individual drugs and medicinal materials.4. English Translation EffortsThe English translation of the General Principles of "China Pharmacopoeia" is a significant and challenging task. It requires not only proficiency in both Chinese and English languages butalso a deep understanding of pharmaceutical science and regulations. The translation process involves the collaboration of experienced translators, pharmaceutical experts, and regulatory professionals. It also requires extensive review, verification, and validation to ensure accuracy and consistency.5. Importance for InternationalizationThe English translation of the General Principles of "China Pharmacopoeia" is crucial for promoting the internationalization of TCM and enhancing global cooperation in pharmaceutical regulation and standardization. It provides international audiences with access to the fundamental principles and standards of Chinese pharmacopoeia, which facilitates mutual understanding and mutual recognition in drug regulation and quality control. Additionally, the English translation serves as a bridge formunication and exchange between Chinese and international pharmaceutical professionals and regulatory authorities.6. ConclusionIn conclusion, the English translation of the General Principles of "China Pharmacopoeia" 2020 Edition is essential for promoting the standardization, regulation, and internationalization ofpharmaceutical products and traditional Chinese medicine. It represents a milestone in the global recognition of Chinese pharmacopoeia and contributes to the advancement of public health and pharmaceutical industry worldwide.In summary, the "China Pharmacopoeia" 2020 Edition carries significant weight in the internationalmunity, and the process of translating it into English is crucial. This English translation of the General Principles is not only a reflection of China'smitment to global standards, but also a catalyst for promoting the internationalization of traditional Chinese medicine. As the world continues to embrace the principles and standards of Chinese pharmacopoeia, the English translation serves as a vital tool for bridging cultural and linguistic gaps in the pharmaceutical industry.。

抗病毒药物达菲

Aquatic Toxicology 96 (2010) 194–202Contents lists available at ScienceDirectAquaticToxicologyj o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /a q u a t oxMixture toxicity of the antiviral drug Tamiﬂu ®(oseltamivir ethylester)and its active metabolite oseltamivir acidBeate I.Escher a ,b ,∗,Nadine Bramaz b ,Judit Lienert b ,Judith Neuwoehner b ,Jürg Oliver Straub caThe University of Queensland,National Research Centre for Environmental Toxicology (Entox),39Kessels Rd,Brisbane,Qld 4108,Australia bEawag,Swiss Federal Institute of Aquatic Science and Technology,8600Dübendorf,Switzerland cF.Hoffmann-La Roche Ltd,Corporate Safety,Health and Environmental Protection,4070Basel,Switzerlanda r t i c l e i n f o Article history:Received 29August 2009Received in revised form 20October 2009Accepted 23October 2009Keywords:Environmental risk assessment Pharmaceuticals AlgaeMetabolite Mixture Tamiﬂu ®a b s t r a c tTamiﬂu ®(oseltamivir ethylester)is an antiviral agent for the treatment of inﬂuenza A and B.The pro-drug Tamiﬂu ®is converted in the human body to the pharmacologically active metabolite,oseltamivir acid,with a yield of 75%.Oseltamivir acid is indirectly photodegradable and slowly biodegradable in sewage works and sediment/water systems.A previous environmental risk assessment has concluded that there is no bioaccumulation potential of either of the compounds.However,little was known about the ecotoxicity of the metabolite.Ester hydrolysis typically reduces the hydrophobicity and thus the toxicity of a compound.In this case,a zwitterionic,but overall neutral species is formed from the charged parent compound.If the speciation and predicted partitioning into biological membranes is considered,the metabolite may have a relevant contribution to the overall toxicity.These theoretical considerations triggered a study to investigate the toxicity of oseltamivir acid (OA),alone and in binary mixtures with its parent compound oseltamivir ethylester (OE).OE and OA were found to be baseline toxicants in the bioluminescence inhibition test with Vibrio ﬁscheri .Their mixture effect lay between predictions for concentration addition and independent action for the mixture ratio excreted in urine and nine additional mixture ratios of OE and OA.In contrast,OE was an order of magnitude more toxic than OA towards algae,with a more pronounced effect when the direct inhibition of photosystem II was used as toxicity endpoint opposed to the 24h growth rate endpoint.The binary mixtures in this assay yielded experimental mixture effects that agreed with predictions for independent action.This is consistent with the ﬁnding that OE exhibits slightly enhanced toxicity,while OA acts as baseline toxicant.Therefore,with respect to mixture classiﬁcation,the two compounds can be considered as acting according to different modes of toxic action,although there are indications that the difference is a toxicokinetic effect,not a true difference of mechanism of toxicity.The general mixture results illustrate the need to consider the role of metabolites in the risk assessment of pharmaceuticals.However,in the concentration ratio of parent to metabolite excreted by humans,the experimental results conﬁrm that the active metabolite does not signiﬁcantly contribute to the risk quotient of the mixture.© 2009 Elsevier B.V. All rights reserved.1.IntroductionOseltamivir ethylester phosphate is used under the trade name of Tamiﬂu ®as an antiviral agent for the treatment and prophylaxis of inﬂuenza A and B.Its mechanism of action is related to the inhi-bition of the inﬂuenza virus neuraminidase (Roche,2006).With the appearance of the bird ﬂu in humans in 2007,and the H1N1pan-demic in 2009,the sales and use of this compound have increased tremendously.Most countries also keep a stock of Tamiﬂu ®to treat∗Corresponding author at:The University of Queensland,National Research Centre for Environmental Toxicology (Entox),39Kessels Rd,Brisbane,Qld 4108,Australia.Tel.:+61732749180;fax:+61732749003.E-mail address:b.escher@.au (B.I.Escher).up to 50%of their population in case of an emergency (Singer et al.,2008).In June 2006,a new “Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use”(EMEA,2006)was released in the European Union,which requires an environmental risk assessment for all marketing authorization applications.It is also of interest to investigate whether compounds that are already on the market pose a hazard to the environ-ment,particularly those with growing market shares like Tamiﬂu ®.A large number of different pharmaceuticals have been detected in surface waters (Ternes,1998;Kolpin et al.,2002).The parent compound of Tamiﬂu ®has not been detected in surface waters yet.However,its active metabolite oseltamivir acid (also called oseltamivir carboxylate)was detected in low ng/L concentrations during the ﬂu season in Japan (Ghosh et al.,2009;Söederströem0166-445X/$–see front matter © 2009 Elsevier B.V. All rights reserved.doi:10.1016/j.aquatox.2009.10.020B.I.Escher et al./Aquatic Toxicology96 (2010) 194–202195et al.,2009).Oseltamivir acid is relatively persistent,showing only indirect photodegradation(Bartels and von Tumpling,2008),slow degradation in surface waters,but increased(microbial)degrada-tion in sediment/water systems(Accinelli et al.,2007;Sacca et al., 2009).Tamiﬂu®manufacturer Roche performed a prospective environ-mental risk assessment according to the EMEA guideline with a few modiﬁcations to account for pandemic use conditions(Straub, 2009).This study concluded that Tamiﬂu®does not pose an envi-ronmental risk.The risk quotient remains below one even under inﬂuenza pandemic conditions,despite very high predicted envi-ronmental concentrations in surface waters,due to its relatively low aquatic ecotoxicity(Straub,2009).Hutchinson et al.(2009) complemented this study by assessing the risk and PBT characteris-tics of oseltamivir acid for the marine environment according to the Technical Guidance document of the EU(European Commission, 2003).They found no environmental risk for the use of Tamiﬂu®in a pandemic situation.According to the EMEA guideline,risk assessment needs to be performed not only on the parent compound but also on the human metabolites,provided they exceed10%of the parent or the parent is a pro-drug(EMEA,2006).Oseltamivir ethylester(OE)is a pro-drug that lacks antiviral activity(Goodman and Gilman,2006).Approx-imately80%of OE is bioavailable after oral administration(He et al.,1999).OE is hydrolyzed by esterases in the liver to oseltamivir acid(OA)under the release of ethanol with a yield of75%and is the active antiviral agent(DrugBank,2006;Goodman and Gilman, 2006;Roche,2006;Straub,2009).No further metabolism occurs and elimination is primarily via urine with60–70%of an oral dose appearing in the urine as the active metabolite(He et al.,1999).The environmental risk assessment of Tamiﬂu®accounted for the metabolite formation by performing toxicity tests both with OE and with a mixture of OE and OA in the ratio of1:4,which cor-responds to the ratio excreted in urine(Straub,2009).The chronic toxicity assays with algae,daphnia andﬁsh performed with this mixture resulted in“No Observed Effect Concentrations”(NOEC) of10,>1,and>1mg/L,respectively(Straub,2009).The PNEC(pre-dicted no effect concentration)of0.1mg/L was derived from the ﬁsh early life stage test with Danio rerio using an assessment factor of10.Even for worst-case exposure under pandemic conditions, the risk analysis indicated no signiﬁcant risk to surface water or sewage works(Straub,2009).A more thorough investigation of the mixture toxicity of OE and OA would be helpful to support the conclusions of this environmen-tal risk assessment because the mixture expected to be excreted to wastewater was used in the risk assessment without resolving the constituents of the mixture.A predictive model of the mixture toxicity of pharmaceuticals and their transformation products had indicated that OA does not signiﬁcantly inﬂuence the overall toxic potential(Lienert et al.,2007).However,the newly published eco-toxicity data(Straub,2009)and a more thorough analysis as well as an improved prediction of the physicochemical parameters of OE and OA for the present study gave rise to the assumption that OA may contribute substantially to the overall mixture toxicity. Therefore it was the aim of this study to perform binary mix-ture experiments with OE and OA with a focus on learning more about their mixture effect and how a parent compound interacts in mixtures with its metabolite but also to substantiate the risk assessment of Tamiﬂu®.It is relatively laborious to perform systematic mixture toxic-ity experiments with chronic tests and given that the NOECs were relatively high,no clear answers would be expected.Mixture toxic-ity experiments were performed using an acute algal toxicity assay because algae proved to be a more sensitive aquatic species than daphnids orﬁsh(Straub,2009).The algal toxicity test was com-plemented by a non-speciﬁc standard bacterial toxicity screening assay,the bioluminescence inhibition test with the marine bac-terium Vibrioﬁscheri(Escher et al.,2008a),which yields information about baseline toxicity and the inhibition of energy transduction.A sound mixture toxicity analysis requires some information on the modes of toxic action of the mixture pounds that have the same target site and act according to the same mode of action are likely to follow the mixture toxicity concept of concentra-tion addition,while compounds that have different target sites act according to independent action(Altenburger et al.,2003).There-fore,prior to studying the mixtures,a mode of action analysis was performed with the single compounds to set up the appropriate hypotheses for the mixture toxicity experiments.The paper is concluded with considerations on the inclusion of metabolites into the risk assessment of pharmaceuticals highlight-ing the example of Tamiﬂu®and the results of the mixture study are related to the recently published environmental risk assessment for Tamiﬂu®(Straub,2009).2.Materials and methods2.1.ChemicalsOseltamivir ethylester phosphate(CAS204255–11–8for phos-phate salt,CAS196618–13–0for free base)and d-tartrate salt of oseltamivir carboxylate(CAS187227–45–8for the OA zwitterion) were kindly provided by F.Hoffmann-La Roche Ltd,Basel,Switzer-land.To avoid any ambiguity related to the molecular weight of the salt and the speciation in solution,all data are reported in molar units.For comparison with literature data,the molecular weights are410.4g/mol for OE phosphate salt and357g/mol for OA tartrate salt.For structures and physicochemical properties refer to Table1.2.2.Chemical analysisThe concentrations of OE in the bioassays were quantiﬁed with HPLC(Summit HPLC System;Dionex,Olten,Switzerland) and UV detection at220nm(UVD340-U,Dionex,Olten,Switzer-land).A reversed-phase C18column(125/4Nucleodur Gravity5m. Macherey-Nagel,Oensingen,Switzerland)was used for separation. The eluent was composed of buffer(10mM ortho-phosphoric acid at pH7)and acetonitrile(70:30).2.3.Bioluminescence inhibition in V.ﬁscheriThe30-min bioluminescence inhibition test with the marine bacterium V.ﬁscheri was used for assessing baseline toxicity and speciﬁc interference with the energy metabolism.It was performed according to ISO guideline11348–3(International Organization for Standardization,1998)with modiﬁcations as described in (Escher et al.,2005b)using freeze-dried bacteria(nge,Düs-seldorf,Germany).The mixture experiments were performed in96-well microtiter plate format after it was conﬁrmed that measured concentrations were equal to nominal concentrations (Escher et al.,2008a).The luminescence output of the bacteria was measured prior to addition of the sample and after30-min incubation(MicroLumatPlus,Berthold Technologies,Regensdorf, Switzerland).The inhibition of bioluminescence was calculated as described in ISO guideline11348–3.The effect concentrations EC50were derived from log-logistic concentration response curves (Escher et al.,2005a,2008b).Full concentration–effect curves were determined for all binary mixture ratios(exact ratios given in Table3).Mixture experiments were performed in a minimum of triplicates and alongside sin-gle compounds.The reported data relate to the bestﬁt of a single concentration–effect curve over all accumulated data(3–10repli-cates).196 B.I.Escher et al./Aquatic Toxicology96 (2010) 194–202Table1Structures and physicochemical properties of oseltamivir ethylester and its human metabolite oseltamivir acid.log K ow a log K lipw b p K a(base)c p K a(acid)c f neutral d log D lipw(pH7)e OE(Oseltamivir ethylester) 1.21 1.617.60–0.201 1.06OA(Oseltamivir acid)0.0060.527.81 3.780.8650.46a Octanol–water partition coefﬁcient,average of various QSARs as cited in Straub(2009).b Liposome–water partition coefﬁcient calculated with Eq.(1).c Acidity constant,estimated using SPARC(Hilal et al.,2005).d Fraction of neutral species at pH7(Schwarzenbach et al.,2003).e Liposome–water distribution ratio at pH7calculated with Eq.(2).2.4.Algal toxicityDirect and indirect effects on photosynthesis were evaluatedwith the24h chlorophyllﬂuorescence test with the green algaeDesmodesmus subspicatus using the chlorophyllﬂuorometer ToxY-PAM according to Escher et al.(2005a).Mixture experimentswere performed with Pseudokirchneriella subcapitata in96-wellmicrotiter plate format(Escher et al.,2008a)after conﬁrmationthat measured concentrations equaled nominal concentrations.Two different algal species were used to ensure consistency withthe baseline toxicity quantitative structure activity relationship(QSAR).Growth conditions were identical for each of the twostrains and both were used in the exponential growth phase.AMaxi-Imaging-PAM(IPAM)(Walz GmbH,Effeltrich,Germany)wasused to determine the yield of photosynthesis Y after2and24h,and optical density(Spectramax®Plus384,Molecular Devices Cor-poration,Sunnyvale,USA)was measured to derive the growthrate during24h.The EC50values for the inhibition of the photo-synthetic yield after2h(EC502h IPAM)or after24h(EC5024h IPAM)and the growth rate inhibition(EC5024h growth)were derived fromlog-logistic concentration–effect curves as described previously(Escher et al.,2008a).The mixture experiments were performedanalogously to those described above,however different concen-tration ratios were used(see Table5).2.5.Speciation and hydrophobicity indicatorsThe liposome–water distribution ratio at pH7,D lipw(pH7),is abetter descriptor for bioaccumulation and hydrophobicity of ioniz-able compounds than the commonly used octanol–water partitioncoefﬁcient K ow(Escher and Hermens,2002)and was therefore usedfor the QSARs.Speciation has to be accounted for when estimat-ing the liposome–water distribution(Schwarzenbach et al.,2003).The liposome–water partition coefﬁcient of the neutral speciesK lipw,neutral was calculated from the estimated octanol–water par-tition coefﬁcient log K ow with Eq.(1),which is valid for polarcompounds(Vaes et al.,1997;Escher et al.,2006).log K lipw,neutral=0.904log K ow+0.515(1)The corresponding K lipw,charged for charged species(charged=anionic or cationic)was assumed to be approximatelyone order of magnitude lower than that of the correspondingneutral species,i.e.log K lipw,charged=log K lipw,neutral−1(Escher andSigg,2004).The D lipw(pH7)was computed with Eq.(2),wheref neutral refers to the fraction of neutral species.log D lipw(pH7)=f neutral log K lipw,neutral+1−f neutral log K lipw,charged(2)2.6.Baseline toxicity versus speciﬁc mode of toxic actionThe toxic ratio TR(Eq.(3))is a measure of the speciﬁcity of amode of toxic action and is deﬁned as the quotient of the predictedbaseline effect concentration EC50baseline toxicity of a given com-pound to its experimentally determined EC50experimental(Verhaaret al.,1992).TR<10corresponds to baseline toxicity,and TR≥10to a speciﬁc mode of toxic action(Verhaar et al.,1992).The higherthe TR,the higher the intrinsic potency of a chemical,i.e.the morepronounced is a speciﬁc mode of toxic action.TR=EC50baseline toxicityEC50experimental(3)The EC50baseline toxicity values were predicted with QSARs takenfrom the literature(European Commission,2003;Escher et al.,2005a).Published QSARs are typically based on the K ow ashydrophobicity descriptor.As discussed above,the K ow is not a suit-able hydrophobicity descriptor for ionized species.However,wehave earlier demonstrated(Escher et al.,2002)that QSARs basedon the D lipw(pH7)are valid for the whole spectrum of neutral,pos-itively and negatively charged molecules,provided that the modeof toxic action is baseline toxicity.Therefore K ow-based literatureQSARs can be rescaled to the liposome–water distribution ratio ofall species at pH7,log D lipw(pH7),as the hydrophobicity descrip-tor by inserting equation1in each QSAR equation(Escher andSchwarzenbach,2002).The resulting QSARs based on log D lipw(pH7)as hydrophobicity descriptor are listed in Table2.The QSAR for the bioluminescence inhibition test in microtiterplate format was experimentally determined for a set of baselineB.I.Escher et al./Aquatic Toxicology96 (2010) 194–202197Table2Measured and modeled EC50values of the parent compound OE for various aquatic endpoints.Organism Endpoint EC50experimental(mM)QSAR equation EC50,parent,baseline QSAR(mM)TR eBacteria Vibroﬁscheri30-minbioluminescenceinhibition 10a log(1/EC50baseline toxicity(M))=0.7log D lipw(pH7)+1.54c4.50.4Algae Selenastrum capricornutum(exp.)or Chlorella vulgaris(QSAR)72h growthinhibition1.1b log(1/EC50baseline toxicity(M))=0.91log D lipw(pH7)+0.63d27.725Algae Desmodesmus subspicatu s PSII inhibition after24h 15.5a log(1/EC50baseline toxicity(M))=0.91log D lipw(pH7)+1.10c9.40.6Waterﬂea Daphnia magna48himmobilization 0.08b log(1/EC50baseline toxicity(M))=0.77log D lipw(pH7)+1.89d2.126Fish Cyprinus carpio(exp.)or Pimephales promelas(QSAR)96h lethality0.24b log(1/LC50baseline toxicity(M))=0.83log D lipw(pH7)+1.46d4.920a Data from this study,performed in vials with experimental veriﬁcation of exposure concentration by HPLC.b Data from Straub(2009).c QSAR from Escher et al.(2005a).d Baseline toxicity QSAR rescaled from K ow-based QSARs from the Technical Guidance Document(TGD)of the EU(European Commission,2003).e Toxic ratio(TR)calculated with Eq.(3).toxicants in ref.(Escher et al.,2008a)(Eq.(4)).log(1/EC50baseline toxicity,Vibrio fischeri(M))=0.84log D lipw(pH7)+1.69(4)The EC50baseline toxicity for the combined algae test is given in equa-tion5for the endpoint24h growth rate and in equation6for the endpoint24h IPAM(Escher et al.,2008a).log(1/EC50baseline toxicity,24h growth(M))=0.95log D lipw(pH7)+1.16(5) log(1/EC50baseline toxicity,24h IPAM(M))=0.84log D lipw(pH7)+1.07(6) 2.7.Mixture toxicity evaluationThe mixture experiments were evaluated with the isobolo-gram method described by Altenburger and Boedeker(1990).Here the experimental EC50value that refers to total molar concen-tration of both components of the binary mixture for a given mixture ratio was multiplied with the fraction of each mixture component.The two axes of the isobologram were constructed from EC50times fraction of OA and EC50times fraction of OE, respectively.The line connecting the two axis intercepts in this isobologram is then equivalent to the model of concentration addi-tion(Altenburger and Boedeker,1990).Although it is not common practice,it is also possible to plot the prediction for independent action into an isobologram,in order to differentiate between inde-pendent action and true antagonism.In this case,for each mixture ratio,a prediction of EC50was performed independently with the equations described in Backhaus et al.(2000).The fractions of OE and OA were multiplied with this predicted value and the result was plotted in the isobologram along with the experimental results.3.Results and discussion3.1.Toxicity of the parent compound OE in the bioluminescence inhibition test in V.ﬁscheriThe30-min EC50values in the30-min bioluminescence inhi-bition test with the marine bacterium V.ﬁscheri of the parent compound oseltamivir ethylester phosphate(OE)were10.5mM (95%conﬁdence interval:7.9–11.2mM)for the test performed according to ISO11348–3(Table2)and10.3mM(95%conﬁdence interval:9.9–10.7mM)using the microtiter plate format(Table3). These values correspond to an EC50value of4.3(4.0–4.6)g/L of OE.According to ISO11348–3,all tested concentrations were con-ﬁrmed by HPLC and refer to aqueous concentrations in the bioassay. The good agreement between the two test setups and between measured and nominal concentrations allowed us to perform all further metabolite and mixture experiments in the microtiter plate format reporting nominal concentrations.3.2.Toxicity of the parent compound OE in the algal toxicity testIn the chlorophyllﬂuorescence test with the green algae D. subspicatus,measuring photosynthesis inhibition after24h using the ToxY-PAM,the EC50was15.5mM(95%conﬁdence interval 14.9–16.2mM),which corresponds to6.4(6.1–6.7)g/L(Table2).P. subcapitata was more sensitive with an EC5024h growth of0.51mM (95%conﬁdence interval0.48–0.55mM)corresponding to210mg/L phosphate salt and an EC5024h IPAM of0.78mM(95%conﬁdence interval0.76–0.81mM)corresponding to319mg/L phosphate salt (Table4).These EC50values are very high,but consistent with the low hydrophobicity of the compound.The values are in the same range as the EC50growth of463mg/L(1.1mM)in the72h algal growth inhibition test with P.subcapitata(Straub,2009).3.3.Toxicity of the metabolite OAThe metabolite oseltamivir acid(OA)was almost equipotent to the parent oseltamivir ethylester phosphate(OE)with an EC50 of6.64mM(95%conﬁdence interval:6.55–6.70mM)for V.ﬁs-cheri,which corresponds to2.4g/L for the used tartrate salt of OA (Table3).In contrast,in the algal toxicity assay,the EC5024h growth of8.3(7.7–8.8)mM and the EC5024h IPAM of19.3(18.2–20.4)mM of OA are16and25times less toxic,respectively,than the corre-sponding EC50values for the parent OE(Table4).The slope of the concentration–effect curve of OA was much steeper than that of OE.The onset of toxicity for OE was relatively fast withﬁrst signs of photosynthesis inhibition after2h.In contrast,the metabolite OA showed<20%of PSII inhibition after2h exposure at concen-trations that lead to100%inhibition of photosynthesis and growth rate after24h(data not shown).This is an observation that could not be rationalized with any mechanistic explanation but will be relevant for the mixture toxicity experiments discussed below.198 B.I.Escher et al./Aquatic Toxicology 96 (2010) 194–202Table 3Descriptors of the log-logistic concentration–effect curves (Escher et al.,2005a )and toxic ratio (TR)analysis for the parent OE and the metabolite OA and their binary mixtures in the bioluminescence inhibition test with Vibrio ﬁscheri using the 96-well plate format.Mixture OE:OA OE fraction (%)log (1/EC50experimental (M))Slope of log-logistic ﬁt EC50experimental (mM)(95%conﬁdence intervals)log (1/EC50baseline )(M)a TR OE100% 1.99±0.01 2.2±0.110.3(10.1–10.5) 2.570.26Mixture 1:0.283% 1.94±0.01 2.5±0.211.6(11.2–12.0)Mixture 1:0.471% 1.91±0.01 3.7±0.312.3(11.9–12.7)Mixture 1:0.663% 1.90±0.01 6.3±0.712.5(12.2–12.8)Mixture 1:0.856% 1.93±0.018.3±1.011.9(11.7–12.1)Mixture 1:150% 1.94±0.01 6.9±0.511.5(11.4–11.6)Mixture 0.8:144% 2.00±0.017.4±0.910.1(9.9–10.3)Mixture 0.6:138% 2.02±0.019.1±1.39.5(9.3–9.7)Mixture 0.4:129% 2.04±0.01 4.4±0.69.0(8.7–9.4)Mixture 0.3:125% 2.06±0.0136.8±2258.6(6.9–10.7)Mixture 0.2:117% 2.10±0.0111.9±2.57.9(7.7–8.0)OA0%2.18±0.0125.5±3.96.6(6.5–6.7)2.08 1.27aQSAR Eq.(4).Table 4Concentration–effect curves and toxic ratio (TR)analysis for the parent OE and the metabolite OA in the algal toxicity test with Pseudokirchneriella subcapitata using the 96-well plate format.EC50experimental (mM)(95%conﬁdence intervals)Slope of log-logistic ﬁt EC50experimental (g/L)b EC50baseline (mM)a TREndpoint 24h growth rate OE 0.51(0.48–0.55) 2.70.21(0.20–0.26)7.013.7OA 8.27(7.75–8.82) 2.5 2.95(2.76–3.15)25.4 3.1Endpoint 24h IPAM OE 0.78(0.76–0.81) 3.10.32(0.31–0.34)10.814.0OA 19.28(18.22–20.39)1.86.88(6.51–7.27)34.41.8a QSAR Eqs.(5)and (6).bBased on phosphate salt for OE and tartrate salt for OA.3.4.Speciation and hydrophobicity indicatorsThe liposome–water partition coefﬁcient of the neutral species K lipw,neutral was calculated from the estimated octanol–water par-tition coefﬁcient log K ow of 1.21for the parent OE and 0.006for the metabolite OA (Straub,2009)using Eq.(1).Note,however,that the limit of applicability of such an equation might be reached consid-ering that OE and OA both have a K ow that is outside the test set domain of the QSAR equation.The predicted log K lipw,neutral is 1.61for OE and 0.46for OA (Table 1).OE is a weak ammonium base and is therefore positively charged at ambient pH.With an estimated acidity constant of 7.6(OE)and7.81(OA)for the basic amino group (estimated with SPARC (Hilal et al.,2005)),the fraction of neutralspecies at pH 7is 20%for OE.16%of OE is in its cationic form,result-ing in a log D lipw (pH 7)of 1.06(Eq.(2)).OA with its acidity constant of the carboxylic acid of 3.78and its retained aliphatic amine func-tion is a zwitterion and overall neutral at pH 7.The log D lipw (pH 7)of OA can therefore be assumed to be equal to log K lipw,neutral .3.5.Toxic ratio analysisAnalysis of the literature data for the parent compound OE revealed that the toxic ratio (TR)varies from 0.4to 26for the different test species (Table 2).In principle,TR >10would be the cut-off value for speciﬁc toxicity.However,for the three species with TR 20–26,there are differences between the tested species andFig.1.Toxic ratio (TR)analysis for (A)the bioluminescence inhibition test with Vibrio ﬁscheri and (B)the 24h growth rate endpoint in the algal toxicity assay with Pseu-dokirchneriella subcapitata .The experimental data of the parent OE and the metabolite OA are depicted with black diamonds.The line corresponds to the baseline toxicity QSAR for the given endpoint,derived from the experimental data of the baseline toxicants depicted with empty circles (Escher et al.,2008a ).(Drawn line:baseline toxicity,TR =1;broken line:speciﬁc mode of toxic action TR ≥10).B.I.Escher et al./Aquatic Toxicology96 (2010) 194–202199Fig.2.(A)Isobologram for the binary mixtures of the parent OE and the metabolite OA in the bioluminescence inhibition test with Vibrioﬁscheri.The drawn line corresponds to the prediction for concentration addition,the broken line to the prediction for independent action.(B)Deviation of the experimental data from the predictions for concentration addition(deviation=(EC50experimental−EC50CA prediction)/EC50experimental,empty circles)and independent action(deviation=(EC50experimental−EC50IA prediction)/EC50experimental,ﬁlled circles).the baseline QSARs that are rescaled from K ow-based QSARs,all of which adds to the uncertainty of the resulting TR value.Therefore no clear conclusions can be drawn.In contrast,the TR remained below10(Fig.1)in all endpoints from literature where the baseline QSAR was established with the same experimental setup,and was deﬁned with experimental D lipw (pH7)values as hydrophobicity descriptors.The calculated toxic ratios(TR)of OE and OA in the30-min bio-luminescence inhibition test with the marine bacterium V.ﬁscheri were0.27and1.27,respectively,indicating that both are baseline toxicants towards V.ﬁscheri(Table3,Fig.1A).Note that OE and OA are at the lower end of hydrophobicity in the baseline toxicity QSAR indicating an overall low toxicity.While the TR values of OA for both24h endpoints in the algal toxicity assay were still in the range to be classiﬁed as baseline tox-icant,the TR of OE were about10times higher than that of OA in both24h endpoints,thus marginally but signiﬁcantly exceeding the threshold value of TR=10(Table4,Fig.1B).This indicates clear differences in the mode of action between OE and OA or a signiﬁ-cant error in the estimation of D lipw(pH7)of OE.The latter is rather unlikely because if D lipw(pH7)of OE was underestimated the TR in V.ﬁscheri would be<0.1,which is an unrealistic value.The differ-ence in the time to effect discussed above supports the conclusion that there is a difference in mode of toxic action.3.6.Mixture toxicityTen different mixture experiments with binary mixtures and varying ratios of OE/OA were performed with the bioluminescence inhibition test of V.ﬁscheri.The resulting EC50values are listed in Table3.When plotting the data in form of an isobologram (Fig.2A)it is evident that the mixture experiments yield higher EC50than the prediction for concentration addition(CA),which corresponds to the straight line connecting the EC50of the two mixture components(Altenburger and Boedeker,1990).This com-bination effect is termed subadditivity(Altenburger and Boedeker, 1990).However,the experimental mixture toxicities are still higher than predictions for independent action(IA).The predictions for IA were performed independently from the isobologram analysis according to Backhaus et al.(2000)and a mixture EC50derived from the prediction for IA was also plotted in the isobologram(as indicated by the broken line in Fig.2A).The deviation of the exper-imental data from the predictions of concentration addition(ﬁlled circles)and independent action(empty circles)is approximately symmetric with a maximum of20–30%deviation from the model (Fig.2B).The TR analysis had clearly indicated that both,parent OE and metabolite OA,act as baseline toxicants.Therefore,the expected mixture toxicity model is concentration addition(Escher et al., 2002),which was not congruent with the experimental observa-tions.A major difference between OE and OA is the gradient of their concentration–effect curves(Fig.3).While OE has a slope typical for a baseline toxicant,the slope of OA is unusually steep(Table3). The mixtures vary in slope depending on the composition.Mix-tures with a higher OA content have a correspondingly higher slope (Table3).For typical binary mixtures,the predictions for concentra-tion addition and independent action are overlapping.Exceptions are binary mixtures of components with largely different slopes as it is observed here.Nevertheless,CA overpredicts the toxicity of the mixture by no more than25%.Cedergreen et al.(2008)recently compared CA and IA as models for mixtures of chemicals with dif-ferent molecular target sites and found that neither of the models was more accurate(Table5).In contrast,in the algal toxicity assay the isobologram for the endpoint24h growth rate clearly shows subadditivity with the experimental data perfectly overlapping with the prediction of independent action(Fig.4A).For the endpoint24h IPAM intheFig.3.Concentration–effect curves for the parent OE,the metabolite OA,and the equimolar mixture in the bioluminescence inhibition test with Vibrioﬁscheri.。

药品英语作文

药品英语作文Medicine is an essential part of our lives, as it helps to alleviate pain, treat illnesses, and improve overall health. The use of medicine has been prevalent throughout history, and it continues to play a crucial role in modern society. In this essay, I will discuss the importance of medicine, the ethical considerations surrounding its use, the impact of pharmaceutical companies, and the future of medicine.First and foremost, medicine is important because it helps to alleviate suffering and improve the quality of life for individuals. Whether it's a simple headache or a more serious illness, medicine provides relief and comfort to those in need. Without medicine, many people would struggle to manage their health conditions and live a fulfilling life. It is crucial to recognize the impact that medicine has on individuals and society as a whole.However, the use of medicine also raises ethical considerations. One of the most pressing issues is the access to medicine, especially in developing countries where many people cannot afford essential medications. This raises questions about the fairness and equality of healthcare, as everyone should have the right to access necessary medicine. Additionally, the overuse of certain medications and the rise of antibiotic resistance are also ethical concerns that need to be addressed. It is important to consider the ethical implications of medicine and strive for a healthcare system that is fair and sustainable.Another important aspect of the medicine industry is the role of pharmaceutical companies. While these companies play a crucial role in developing and producing medications, there are also concerns about their influence on healthcare. The high cost of prescription drugs and the marketing tactics used by pharmaceutical companies have come under scrutiny. It is essential to strike a balance between the need for innovation and profit in the pharmaceutical industry and the ethical responsibility to provide affordable and accessible medicine to all.Looking towards the future, the field of medicine is constantly evolving, with new advancements and breakthroughs being made. From personalized medicine to gene editing, there are exciting developments that have the potential to revolutionize healthcare. However, it is important to approach these advancements with caution and consider the ethical and social implications. As we continue to progress in the field of medicine, it is crucial to prioritize the well-being of individuals and society as a whole.In conclusion, medicine is an essential part of our lives, providing relief, treating illnesses, and improving overall health. However, it is important to consider the ethical considerations surrounding its use, the impact of pharmaceutical companies, and the future of medicine. By addressing these issues, we can strive to create a healthcare system that is fair, accessible, and focused on the well-being of all individuals.。

苯磺酸氨氯地平片英文说明书

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed touse amlodipine besylate tablets safely and effectively. See full prescribing information for amlodipine besylate tablets. Amlodipine Besylate Tablets Initial U.S. Approval: 1987INDICATIONS AND USAGEAmlodipine besylate tablets are a calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of:•Hypertension ( ) 1.1•Coronary Artery Disease ( ) 1.2•Chronic Stable Angina•Vasospastic Angina (Prinzmetal's or Variant Angina)•Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40%DOSAGE AND ADMINISTRATION•Adult recommended starting dose: 5 mg once daily with maximum dose 10 mg once daily. ( ) 2.1•Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily. ( ) 2.1•Pediatric starting dose: 2.5 mg to 5 mg once daily. ( ) 2.2: Doses in excess of 5 mg daily have not been studied in pediatric patients. ( ) Important Limitation2.2DOSAGE FORMS AND STRENGTHS• 2.5 mg, 5 mg, and 10 mg Tablets ( ) 3CONTRAINDICATIONS•Known sensitivity to amlodipine ( ) 4WARNINGS AND PRECAUTIONS •Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, because of the gradual onset of action, acute hypotension is unlikely. ( ) 5.1•Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease. ( ) 5.2•Titrate slowly when administering calcium channel blockers to patients with severe hepatic impairment. ( ) 5.4ADVERSE REACTIONSMost common adverse reactions are headache and edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence >1% are headache, fatigue, nausea, abdominal pain, and somnolence. ( ) 6To report SUSPECTED ADVERSE REACTIONS, contact Qualitest Pharmaceuticals at 1-800-444-4011 or FDA at 1-800-FDA-1088 or /medwatch.To report SUSPECTED ADVERSE REACTIONS, contact at or FDA at 1-800-FDA-1088 or /medwatchUSE IN SPECIFIC POPULATIONS •Pregnancy: Use only if the potential benefit justifies the potential risk. ( ) 8.1•Nursing: Discontinue when administering amlodipine. ( ) 8.3•Pediatric: Effect on patients less than 6 years old is not known. ( ) 8.4•Geriatric: Start dosing at the low end of the dose range, due to thegreater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. ( ) 8.5Revised: 05/2010FULL PRESCRIBING INFORMATION: CONTENTS *1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS6 ADVERSE REACTIONS7 DRUG INTERACTIONS7.10 Drug/Laboratory Test Interactions8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics and Metabolism12.4 Pediatric Patients13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIESAMLODIPINE 5MG TABLET* Sections or subsections omitted from the full prescribing information are not listedFULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION3 DOSAGE FORMS AND STRENGTHS2.5, 5, and 10 mg Tablets4 CONTRAINDICATIONSAmlodipine is contraindicated in patients with known sensitivity to amlodipine.5 WARNINGS AND PRECAUTIONS6 ADVERSE REACTIONS7 DRUG INTERACTIONS7.10 Drug/Laboratory Test InteractionsNone known.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category C There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day (respectively, 8 times and 23 times the maximum recommended human dose of 10 mg on a mg/m basis) during their respective periods of major organogenesis. However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. Amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose. 1121Based on patient weight of 50 kg.8.3 Nursing MothersIt is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while amlodipine is administered.8.4 Pediatric UseEffect of amlodipine on blood pressure in patients less than 6 years of age is not known.8.5 Geriatric UseClinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required . [see ] Dosage and Administration (2.1)10 OVERDOSAGEOverdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited.Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m basis) caused a marked peripheral vasodilation and hypotension. 2If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors(such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.11 DESCRIPTIONAmlodinpine besylate is the besylate salt of amlodipine, a long-acting calcium channel blocker.Amlodipine besylate is chemically described as 3-Ethyl-5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulphonate. Its molecular formula is C H ClN O •C H O S, and its structural formula is: 202525663Amlodipine besylate is a white crystalline powder with a molecular weight of 567.1. It is slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate tablets are formulated as white tablets equivalent to 2.5, 5, and 10 mg of amlodipine fororal administration. In addition to the active ingredient, amlodipine besylate, each tablet contains the following inactive ingredients: dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.12 CLINICAL PHARMACOLOGY12.1 Mechanism of ActionAmlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscleare dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. in vitroAmlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.The precise mechanisms by which amlodipine relieves angina have not been fully delineated, but are thought to include the following: 12.2 Pharmacodynamics12.3 Pharmacokinetics and MetabolismAfter oral administration of therapeutic doses of amlodipine, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64 and 90%. The bioavailability of amlodipine is not altered by the presence of food.Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination half-life of about 30–50 hours. Steady-state plasma levels of amlodipine are reached after 7 to 8 days of consecutive daily dosing. Ex vivoThe pharmacokinetics of amlodipine are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose.Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40–60%, and a lower initial dose may be required. A similar increase in AUC was observed in patients with moderate to severe heart failure.12.4 Pediatric PatientsSixty-two hypertensive patients aged 6 to 17 years received doses of amlodipine between 1.25 mg and 20 mg. Weight-adjusted clearance and volume of distribution were similar to values in adults.13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityRats and mice treated with amlodipine maleate in the diet for up to two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 amlodipine mg/kg/day, showed no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was, on a mg/m basis, similar to the maximum recommended human dose of 10 mg amlodipine/day. For the rat, the highest dose was, on a mg/m basis, about twice the maximum recommended human dose. 2222Mutagenicity studies conducted with amlodipine maleate revealed no drug related effects at either the gene or chromosome level. There was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and females for 14 days prior to mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose of 10 mg/day on a mg/m basis). 222Based on patient weight of 50 kg14 CLINICAL STUDIESPATIENT INFORMATION AMLODIPINE BESYLATE TABLETSRead this information carefully before you start taking and each time you refill your prescription. There may be new information. This information does not replace talking with your doctor. If you have any questions about , ask your doctor. Your doctor will know if is right for you. amlodipineamlodipineamlodipineis a type of medicine known as a calcium channel blocker (CCB). It is used to treat high blood pressure (hypertension) and a type of chest pain called angina. It can be used by itself or with other medicines to treat these conditions. What is ? amlodipine AmlodipineHigh blood pressure comes from blood pushing too hard against your blood vessels. relaxes your blood vessels, which lets your blood flow more easily and helps lower your blood pressure. Drugs that lower blood pressure lower your risk of having a stroke or heart attack. High Blood Pressure (hypertension)AmlodipineAngina is a pain or discomfort that keeps coming back when part of your heart does not get enough blood. Angina feels like a pressing or squeezing pain, usually in your chest under the breastbone. Sometimes you can feel it in your shoulders, arms, neck, jaws, or back. can relieve this pain. AnginaAmlodipineDo not use if you are allergic to amlodipine (the active ingredient in ), or to the inactive ingredients. Your doctor or pharmacist can give you a list of these ingredients. Who should not use amlodipine?amlodipine besylate tablets amlodipine besylate tabletsTell your doctor about any prescription and non-prescription medicines you are taking, including natural or herbal remedies. Tell your doctor if you: What should I tell my doctor before taking ? amlodipine•ever had heart disease•ever had liver problems•are pregnant, or plan to become pregnant. Your doctor will decide if is the best treatment for you. amlodipine•are breastfeeding. Do not breastfeed while taking . You can stop breastfeeding or take a different medicine. amlodipineHow should I take ? amlodipine•Take once a day, with or without food. You can take with most drinks, including grapefruit juice. amlodipineamlodipine•It may be easier to take your dose if you do it at the same time every day, such as with breakfast or dinner, or at bedtime. Do not take more than one dose of at a time. amlodipine•If you miss a dose, take it as soon as you remember. Do not take if it has been more than 12 hours since you missed your last dose. Wait and take the next dose at your regular time. amlodipine•You can use nitroglycerin and together. If you take nitroglycerin for angina, don't stop taking it while you are taking Other medicines:amlodipineamlodipine.•While you are taking , do not stop taking your other prescription medicines, including any other blood pressure medicines, without talking to your doctor. amlodipine•If you took too much , call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away. amlodipineWhat should I avoid while taking ? amlodipine•breastfeed. It is not known if will pass through your milk. Do notamlodipine•start any new prescription or non-prescription medicines or supplements, unless you check with your doctor first. Do notmay cause the following side effects. Most side effects are mild or moderate: What are the possible side effects of ? amlodipine Amlodipine•headache•swelling of your legs or ankles•tiredness, extreme sleepiness•stomach pain, nausea•dizziness•flushing (hot or warm feeling in your face)•arrhythmia (irregular heartbeat)•heart palpitations (very fast heartbeat)It is rare, but when you first start taking or increase your dose, you may have a heart attack or your angina may get worse. If that happens, call your doctor right away or go directly to a hospital emergency room. amlodipineTell your doctor if you are concerned about any side effects you experience. These are not all the possible side effects of . For a complete list, ask your doctor or pharmacist. amlodipineCall your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or by visiting /medwatch.Keep away from children. Store at 20° to 25°C (between 68° and 77°F) [see USP Controlled Room Temperature]. Keep out of the light. Do not store in the bathroom. Keep in a dry place. How do I store ? amlodipineamlodipineamlodipinebesylate tabletsamlodipineamlodipineSometimes, doctors will prescribe a medicine for a condition that is not written in the patient information leaflets. Only use the way your doctor told you to. Do not give to other people, even if they have the same symptoms you have. It may harm them. General advice about amlodipineamlodipineamlodipineYou can ask your pharmacist or doctor for information about . amlodipineManufactured for: Huntsville, AL 35811QUALITEST PHARMACEUTICALS8182524 Revised: 5/2010 R3AMLODIPINE 5MG TABLETRevised: 05/2010Distributed by: Unit Dose Services。

pharmaceutics英文解释

pharmaceutics英文解释Pharmaceutics refers to the science of designing and formulating drugs or medications for use in the treatment and prevention of diseases. It involves a range of aspects including the processing, manufacturing, and development of drugs, as well as their delivery systems to the body.Pharmaceutics is an interdisciplinary field that draws heavily from chemistry, biology, and engineering to develop new drugs and improve existing ones. It involves the study of pharmacokinetics, which looks at how drugs are absorbed, distributed, metabolized, and excreted by the body. It also involves the study of pharmacodynamics, which looks at how drugs interact with their target molecules and produce their therapeutic effects.One of the major areas of focus in pharmaceutics is drug delivery systems. These are designed to enhance the effectiveness of drug therapy by controlling where and howthe drug is released in the body. Drug delivery systemsinclude various forms of drug formulations such as tablets, capsules, injections, transdermal patches, inhalers, and more. They can also include innovative technologies such as nanoparticles that can be used to deliver drugs directly to specific cells or tissues.Another important aspect of pharmaceutics is quality control. This involves ensuring that drugs are manufacturedto meet certain safety and efficacy standards. Qualitycontrol involves testing raw materials and finished productsto ensure that they meet requirements, as well as monitoringmanufacturing processes to ensure that they are consistent and reliable.Pharmaceutics plays a crucial role in improving public health by providing modern drugs that can effectively treat diseases and improve quality of life. It has also helped to address issues such as drug resistance and drug toxicity, by developing new drugs and delivery systems that are lesslikely to cause harm to patients.Overall, pharmaceutics is a complex and dynamic field that is constantly evolving to meet the needs of patients and healthcare professionals. With ongoing research and development, it has the potential to greatly improve healthcare outcomes and address some of the most pressing medical challenges of our time.。

苯磺酸氨氯地平片英文说明书

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed touse amlodipine besylate tablets safely and effectively. See full prescribing information for amlodipine besylate tablets. Amlodipine Besylate Tablets Initial U.S. Approval: 1987INDICATIONS AND USAGEAmlodipine besylate tablets are a calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of:•Hypertension ( ) 1.1•Coronary Artery Disease ( ) 1.2•Chronic Stable Angina•Vasospastic Angina (Prinzmetal's or Variant Angina)•Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40%DOSAGE AND ADMINISTRATION•Adult recommended starting dose: 5 mg once daily with maximum dose 10 mg once daily. ( ) 2.1•Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily. ( ) 2.1•Pediatric starting dose: 2.5 mg to 5 mg once daily. ( ) 2.2: Doses in excess of 5 mg daily have not been studied in pediatric patients. ( ) Important Limitation2.2DOSAGE FORMS AND STRENGTHS• 2.5 mg, 5 mg, and 10 mg Tablets ( ) 3CONTRAINDICATIONS•Known sensitivity to amlodipine ( ) 4WARNINGS AND PRECAUTIONS •Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, because of the gradual onset of action, acute hypotension is unlikely. ( ) 5.1•Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease. ( ) 5.2•Titrate slowly when administering calcium channel blockers to patients with severe hepatic impairment. ( ) 5.4ADVERSE REACTIONSMost common adverse reactions are headache and edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence >1% are headache, fatigue, nausea, abdominal pain, and somnolence. ( ) 6To report SUSPECTED ADVERSE REACTIONS, contact Qualitest Pharmaceuticals at 1-800-444-4011 or FDA at 1-800-FDA-1088 or /medwatch.To report SUSPECTED ADVERSE REACTIONS, contact at or FDA at 1-800-FDA-1088 or /medwatchUSE IN SPECIFIC POPULATIONS •Pregnancy: Use only if the potential benefit justifies the potential risk. ( ) 8.1•Nursing: Discontinue when administering amlodipine. ( ) 8.3•Pediatric: Effect on patients less than 6 years old is not known. ( ) 8.4•Geriatric: Start dosing at the low end of the dose range, due to thegreater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. ( ) 8.5Revised: 05/2010FULL PRESCRIBING INFORMATION: CONTENTS *1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS6 ADVERSE REACTIONS7 DRUG INTERACTIONS7.10 Drug/Laboratory Test Interactions8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics and Metabolism12.4 Pediatric Patients13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIESAMLODIPINE 5MG TABLET* Sections or subsections omitted from the full prescribing information are not listedFULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION3 DOSAGE FORMS AND STRENGTHS2.5, 5, and 10 mg Tablets4 CONTRAINDICATIONSAmlodipine is contraindicated in patients with known sensitivity to amlodipine.5 WARNINGS AND PRECAUTIONS6 ADVERSE REACTIONS7 DRUG INTERACTIONS7.10 Drug/Laboratory Test InteractionsNone known.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category C There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day (respectively, 8 times and 23 times the maximum recommended human dose of 10 mg on a mg/m basis) during their respective periods of major organogenesis. However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. Amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose. 1121Based on patient weight of 50 kg.8.3 Nursing MothersIt is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while amlodipine is administered.8.4 Pediatric UseEffect of amlodipine on blood pressure in patients less than 6 years of age is not known.8.5 Geriatric UseClinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required . [see ] Dosage and Administration (2.1)10 OVERDOSAGEOverdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited.Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m basis) caused a marked peripheral vasodilation and hypotension. 2If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors(such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.11 DESCRIPTIONAmlodinpine besylate is the besylate salt of amlodipine, a long-acting calcium channel blocker.Amlodipine besylate is chemically described as 3-Ethyl-5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulphonate. Its molecular formula is C H ClN O •C H O S, and its structural formula is: 202525663Amlodipine besylate is a white crystalline powder with a molecular weight of 567.1. It is slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate tablets are formulated as white tablets equivalent to 2.5, 5, and 10 mg of amlodipine fororal administration. In addition to the active ingredient, amlodipine besylate, each tablet contains the following inactive ingredients: dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.12 CLINICAL PHARMACOLOGY12.1 Mechanism of ActionAmlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscleare dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. in vitroAmlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.The precise mechanisms by which amlodipine relieves angina have not been fully delineated, but are thought to include the following: 12.2 Pharmacodynamics12.3 Pharmacokinetics and MetabolismAfter oral administration of therapeutic doses of amlodipine, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64 and 90%. The bioavailability of amlodipine is not altered by the presence of food.Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination half-life of about 30–50 hours. Steady-state plasma levels of amlodipine are reached after 7 to 8 days of consecutive daily dosing. Ex vivoThe pharmacokinetics of amlodipine are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose.Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40–60%, and a lower initial dose may be required. A similar increase in AUC was observed in patients with moderate to severe heart failure.12.4 Pediatric PatientsSixty-two hypertensive patients aged 6 to 17 years received doses of amlodipine between 1.25 mg and 20 mg. Weight-adjusted clearance and volume of distribution were similar to values in adults.13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityRats and mice treated with amlodipine maleate in the diet for up to two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 amlodipine mg/kg/day, showed no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was, on a mg/m basis, similar to the maximum recommended human dose of 10 mg amlodipine/day. For the rat, the highest dose was, on a mg/m basis, about twice the maximum recommended human dose. 2222Mutagenicity studies conducted with amlodipine maleate revealed no drug related effects at either the gene or chromosome level. There was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and females for 14 days prior to mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose of 10 mg/day on a mg/m basis). 222Based on patient weight of 50 kg14 CLINICAL STUDIESPATIENT INFORMATION AMLODIPINE BESYLATE TABLETSRead this information carefully before you start taking and each time you refill your prescription. There may be new information. This information does not replace talking with your doctor. If you have any questions about , ask your doctor. Your doctor will know if is right for you. amlodipineamlodipineamlodipineis a type of medicine known as a calcium channel blocker (CCB). It is used to treat high blood pressure (hypertension) and a type of chest pain called angina. It can be used by itself or with other medicines to treat these conditions. What is ? amlodipine AmlodipineHigh blood pressure comes from blood pushing too hard against your blood vessels. relaxes your blood vessels, which lets your blood flow more easily and helps lower your blood pressure. Drugs that lower blood pressure lower your risk of having a stroke or heart attack. High Blood Pressure (hypertension)AmlodipineAngina is a pain or discomfort that keeps coming back when part of your heart does not get enough blood. Angina feels like a pressing or squeezing pain, usually in your chest under the breastbone. Sometimes you can feel it in your shoulders, arms, neck, jaws, or back. can relieve this pain. AnginaAmlodipineDo not use if you are allergic to amlodipine (the active ingredient in ), or to the inactive ingredients. Your doctor or pharmacist can give you a list of these ingredients. Who should not use amlodipine?amlodipine besylate tablets amlodipine besylate tabletsTell your doctor about any prescription and non-prescription medicines you are taking, including natural or herbal remedies. Tell your doctor if you: What should I tell my doctor before taking ? amlodipine•ever had heart disease•ever had liver problems•are pregnant, or plan to become pregnant. Your doctor will decide if is the best treatment for you. amlodipine•are breastfeeding. Do not breastfeed while taking . You can stop breastfeeding or take a different medicine. amlodipineHow should I take ? amlodipine•Take once a day, with or without food. You can take with most drinks, including grapefruit juice. amlodipineamlodipine•It may be easier to take your dose if you do it at the same time every day, such as with breakfast or dinner, or at bedtime. Do not take more than one dose of at a time. amlodipine•If you miss a dose, take it as soon as you remember. Do not take if it has been more than 12 hours since you missed your last dose. Wait and take the next dose at your regular time. amlodipine•You can use nitroglycerin and together. If you take nitroglycerin for angina, don't stop taking it while you are taking Other medicines:amlodipineamlodipine.•While you are taking , do not stop taking your other prescription medicines, including any other blood pressure medicines, without talking to your doctor. amlodipine•If you took too much , call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away. amlodipineWhat should I avoid while taking ? amlodipine•breastfeed. It is not known if will pass through your milk. Do notamlodipine•start any new prescription or non-prescription medicines or supplements, unless you check with your doctor first. Do notmay cause the following side effects. Most side effects are mild or moderate: What are the possible side effects of ? amlodipine Amlodipine•headache•swelling of your legs or ankles•tiredness, extreme sleepiness•stomach pain, nausea•dizziness•flushing (hot or warm feeling in your face)•arrhythmia (irregular heartbeat)•heart palpitations (very fast heartbeat)It is rare, but when you first start taking or increase your dose, you may have a heart attack or your angina may get worse. If that happens, call your doctor right away or go directly to a hospital emergency room. amlodipineTell your doctor if you are concerned about any side effects you experience. These are not all the possible side effects of . For a complete list, ask your doctor or pharmacist. amlodipineCall your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or by visiting /medwatch.Keep away from children. Store at 20° to 25°C (between 68° and 77°F) [see USP Controlled Room Temperature]. Keep out of the light. Do not store in the bathroom. Keep in a dry place. How do I store ? amlodipineamlodipineamlodipinebesylate tabletsamlodipineamlodipineSometimes, doctors will prescribe a medicine for a condition that is not written in the patient information leaflets. Only use the way your doctor told you to. Do not give to other people, even if they have the same symptoms you have. It may harm them. General advice about amlodipineamlodipineamlodipineYou can ask your pharmacist or doctor for information about . amlodipineManufactured for: Huntsville, AL 35811QUALITEST PHARMACEUTICALS8182524 Revised: 5/2010 R3AMLODIPINE 5MG TABLETRevised: 05/2010Distributed by: Unit Dose Services。

四环素类抗生素生物降解研究进展

四环素类抗生素生物降解研究进展郑茂佳;张恩栋;孙静茹;王冬莹【摘要】四环素类抗生素是一类以并四苯结构为母核的广谱抗生素,被广泛应用于医疗、畜牧、水产等行业,通过粪便和尿液排出造成土壤、水体严重污染.本文概括了四环素类抗生素的微生物降解、植物修复、人工湿地以及微生物燃料电池的降解机理、影响因素和研究进展,以期为其生物降解后续研究提供参考.%Tetracycline antibiotics are a class of broad-spectrum antibiotics with the tetracene structure as the mother nucleus. It has been widely used in the medical industry, animal husbandry, aquaculture and other industries. However, most of them were excreted in the form of excrement and urine, causing serious pollution problems of soil and water. The degradation mechanism, influencing fac-tors and progress of microbial degradation, phytoremediation, constructed wetlands and microbial fuel cells in the biodegradation stud-ies of tetracycline antibiotics were summarized in the review, aiming to provide references for further research.【期刊名称】《天津农业科学》【年(卷),期】2018(024)006【总页数】6页(P72-76,85)【关键词】四环素类抗生素;微生物降解;植物修复;人工湿地;微生物燃料电池【作者】郑茂佳;张恩栋;孙静茹;王冬莹【作者单位】辽宁师范大学生命科学学院,辽宁大连 116081;辽宁师范大学生命科学学院,辽宁大连 116081;辽宁师范大学生命科学学院,辽宁大连 116081;辽宁师范大学生命科学学院,辽宁大连 116081【正文语种】中文【中图分类】X53四环素类抗生素（Tetracycline antibiotics，TCs）是由链霉菌产生的一类广谱抗生素，阻止氨酰tRNA同核蛋白结合产生药理作用[1]，抑制革兰氏阳性和阴性菌、支原体、衣原体、立克次氏体及滤过性病毒等微生物生理活性[2]。

参考文献——精选推荐

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HPLC-ELSD法测定硫酸核糖霉素的含量和有关物质

HPLC-ELSD法测定硫酸核糖霉素的含量和有关物质刘海玲;曹晓云【摘要】目的建立硫酸核糖霉素含量和有关物质的分析方法,为该类药提供质量控制标准.方法应用高效液相色谱-蒸发光散射检测器(HPLC-ELSD)法测定硫酸核糖霉素含量和有关物质.采用Agela Technologies Venusil ASB-C18 15nm (250mm×4.6mm,5μm)色谱柱,流动相为0.11mol/L七氟丁酸酐混合溶液[称取七氟丁酸酐45.1g,置1000mL量瓶中,加乙腈-四氧呋喃-水(8∶5∶87)混合溶液溶解并稀释至刻度,摇匀],流速为0.8mL/min,漂移管温度为110℃,雾化气体流速为3.0L/min.结果在选定色谱条件下,核糖霉素和有关物质分离良好.核糖霉素在0.34～2.68μg范围内进样量对数与峰面积对数间呈较好的线性关系(r=0.9988),最低检出量为68ng.结论方法快速、简便,结果准确可靠,重现性好,可用于含量测定和有关物质检测.【期刊名称】《中国抗生素杂志》【年(卷),期】2010(035)009【总页数】4页(P684-687)【关键词】硫酸核糖霉素;高效液相色谱;蒸发光散射检测器;含量测定;有关物质【作者】刘海玲;曹晓云【作者单位】天津市药品检验所,天津,300070;天津市药品检验所,天津,300070【正文语种】中文【中图分类】R927.2硫酸核糖霉素为氨基糖苷类广谱抗生素，由于氨基糖苷类抗生素无特征紫外吸收，不能直接采用传统HPLC-UV法测定，采用衍生化方法测定试验结果影响因素多，无法明确判断检测到的杂质来源，限制了衍生化法在氨基糖苷类抗生素有关物质检测方面的应用。

蒸发光散射检测器(ELSD)为不含发色团化合物的分析提供了一种新的检测手段，其响应值与被测物质量成正比，不依赖于被测物质的光学性质[1]。

近年来陆续有文献报道用蒸发光散射检测器进行氨基糖苷类抗生素的质量分析[2-5]。

分光光度法测定维生素C的含量外文翻译原文

1 IntroductionVitamin C occurs in different concentrations in a vari-ety of natural samples. It is added to several pharma-ceutical products as an essential ingredient, a stabilizer for vitamin B complex, and as an antioxidant.Consequent upon its desirable effects, it is widely used in the treatment of certain diseases such as scurvy,common cold, anemia, haemorrhagic disorders, wound healing, and even infertility, to mention some stark cases. It is considered essential for the development and regeneration of muscles, bones, teeth and skin.The increasing use of pharmaceuticals and other natural samples containing vitamin C has meant that the practi-cising chemists should develop analytical procedures for its determination which are simple to operate, rapid,accurate, sensitive and selective. The desire to develop methods with ideal characteristics has resulted a large number of procedures with varying applicability. Many instrument-based analyses including fluorometry 1–4,HPLC 5–10, polarography 11–13and enzymatic 14,15methods are reported in the literature. But due to their inherent limitations, these techniques are not commonly used for routine analyses. However, photometric methods are particularly attractive because of their speed and sim-plicity. Consequently, a large number of such proce-dures have been developed for the determination of ascorbic acid (AA). Though some short reviews 16–18have been reported, a critical assessment of these meth-ods is desirable to examine their salient features and utility. This review is an attempt to assess exclusively the existing spectrophotometric methods for the deter-mination of vitamin C as regards their simplicity, rapid-ity, Beer’s law range, sensitivity, selectivity and applic-ability. It is primarily based on the information collect-ed through the Chemical Abstracts for the period 1970to mid-1997.2 Results and DiscussionSeveral dyes such as 2,6-dichlorophenolindophenol (DCIP), dimethoxydiquinone (DMDQ), ninhydrin, fast red AL salt and 2′,7′-dichlorofluorescein etc . have been used for the determination of vitamin C. Among these dyes, DCIP has been most extensively studied. It is included in the official titrimetric methods as reported in different pharmacopoeias 19–21and it also forms the basis of many colorimetric methods. The blue dye DCIP is reduced to the colorless form on addition of ascorbic acid as shown in Fig.1, but it gives a pink color to the acidic solutions. Using the dye, ascorbic acid present in human urine 22and processed potatoes 23has been determined. The excess dye can be extracted with xylene or butanol.24Many substances which are capable of reducing the dye resulting from the prepara-tion and processing of food samples interfere. Flow dialysis proposed by Gary et al .25and continuous flow systems have been used to monitor the decrease in absorbance of DCIP. Such automated systems appear to be justified only when routine analysis of a largeANALYTICAL SCIENCES OCTOBER 1998, VOL. 14Photometric Methods for the Determination of Vitamin CSatya P. A RYA †, Meenakshi M AHAJAN and Preeti J AINDepartment of Chemistry, Kurukshetra University, Kurukshetra –136119, Haryana State, IndiaThe importance of vitamin C to the human body is widely acknowledged throughout the globe. The deficiency of this vitamin leads to various diseases. In view of its importance, numerous methods including spectrophotometric ones have been developed for its determination in pharmaceuticals, foods and biological samples. A comprehensive review of the available spectophotometric methods for the determination of ascorbic acid is presented.Keywords Vitamin C determination, spectrophotometric method†To whom correspondence should be addressed.Fig.1The reduction of DCIP with ascorbic acid.Ascorbic acidDCIP(Oxidized, Blue-Pink)Dehydroascorbic acid DCIP (Reduced, Colorless)number of samples is needed; otherwise it is tedious to use for a single estimation.Dimethoxydiquinone 26gives a violet-colored product with ascorbic acid in a phosphate buffer (pH 6.6). The reduced “indigoid” quinhydrone form is perhaps responsible for the formation of violet-colored product as shown in Fig. 2. After diluting with dioxane,absorbance of the colored solution which is stable over 24 h only under dark conditions is measured at 510 nm.Heating leads to a decrease in color intensity. Beer’s law holds good up to 80 µg ml –1with a detection limit of 10 µg ml –1. Riboflavin and copper interfere. The interference of iron(II) sulfate responsible for precipita-tion can be removed by centrifugation. Though the method is not sufficiently sensitive (ε=1.62×103), it can still be applied to the analysis of citrus fruits 27after extracting the colored product into chloroform (λmax =530 nm). Lin et al .28and Pandey 29reported pro-cedures based on the reaction of ascorbic acid with fast Red AL salt (1)(zinc chloride salt of diazotized 1-aminoanthraquinone) and tetrachlorobenzoquinone (2).The reaction of (1)proceeds in acid medium but the blue color develops only after the addition of alkali,which exhibits three absorption bands between 500–630 nm. If one uses the latter reagent (2), ascorbic acid is determined at 336 nm (ε=535 cm 2mol –1) via a decrease in absorbance of 7×10–4M tetrachlorobenzo-quinone (chloranil) in 80% acetone –water (v/v) medi-um. With these methods, mixtures of ascorbic acid with thiols like o -mercaptobenzoic acid, mercaptosuc-cinic acid, 3-mercaptopropionic acid can not be resolved.Methylene Blue 30, (3)and ninhydrin 31,32(4)find applications with the determination of ascorbic acid in food products. The colorless form of the dye (3)is extracted into chloroform after its reduction with ascor-bic acid; back oxidation of the dihydro derivative to Methylene Blue has been used for the assay of ascorbic acid (λmax =653 nm). The method is reported to be highly sensitive. The reaction of ascorbic acid with ninhydrin carried out on a boiling water bath using 80% aqueous solution as a medium in 0.01 M NH 4OH is used for its determination in pharmaceuticals (λmax =415 nm), but without added advantages.In the sixties, many methods based on the coupling of ascorbic acid with aniline diazonium salts were report-ed. A purplish or blue colored species is produced by these salts with ascorbic acid in alkaline medium.Diazotized-4-methoxy-2-nitroaniline couples withascorbic acid in oxalic acid medium in the presence of ethanol or isopropanol, giving a purplish color in alka-line solutions. Though Fe(II), Sn(II) and dehydroascor-bic acid (DHAA) do not interfere, the presence of reductones and reductic acid requires formaldehyde condensation. Low contents of vitamin C in the pres-ence of flavanoids and pectic substances are also detected. The reaction of ascorbic acid with 4-nitrobenzene diazonium fluoroborate in acetic acid medium was used for its determination at λmax 415 nm.But the mixture has to be kept for 25 min in the dark,followed by the addition of sodium hydroxide. The sensitivity of a large number of stabilized diazonium salts was evaluated; diazotized 4-nitroaniline-2:5-dimethoxy-aniline was found to give the most intense color reaction.Enzymic 33–35colorimetric determinations of ascorbic acid in commercial vitamin C tablets and in fruits and vegetables were made by measuring the absorbance at 358 nm or 320 nm of the resulting products obtained by oxidation of o -phenylenediamine/1,4-diaminobenzene using ascorbate oxidase or peroxidase in presence of H 2O 2at pH 5.3. Ascorbic acid is determined after oxi-dation with mercuric chloride and condensing the DHAA with 4,5-disubstituted phenylenediamine 36,which gives the quinoxaline derivative used for absorbance measurement. The method involving 4-nitro-1,2-phenylenediamine 37(λmax =375 nm) is very complex and laborious, since it involves many time-consuming steps including purification of the sample with anionic Sephadex column.In the recent past, the determination of oxidized and reduced vitamin C in pharmaceuticals, foods and bio-logical samples has gained importance since AA and DHAA redox couple is an important component of many biological systems. Simultaneous measurement of both AA and DHAA using HPLC has been carried out by various workers 38–45in different laboratories.Rose and Nahrwold 38determined AA and DHAA by monitoring UV absorbance at 254 nm and 210 nm respectively for the analysis of foods, biological sam-ples and pharmaceutical preparations. Graham and Donald 39have carried out the analysis at 254 nm after extracting the food samples with 62.5 mM metaphos-phoric acid using an ion exchange column (Aminex-HPX 87H). Both these forms have also been deter-mined in vegetable samples 40using a UV detector (254nm). Yasui and Hayashi 41made such determinations by converting to compounds having λmax at 300 nm under alkaline conditions. Derivatization of DHAA is accel-erated in the presence of sodium borohydride.Validation of the micromethod for the determination of the oxidized and reduced vitamin C in plasma by HPLC fluorescence method has been reported by Tessier et al .45These methods are useful and a single step HPLC assay of such detections has been helpful in overcoming the burden of derivatization.Ascorbic acid gives colored species with substituted benzene such as m -dinitrobenzene 46in formaldehydeFig.2Reduction reaction of dimethoxydiquinone (DMDQ).‘Indigoid’quinhydroneDMDQand trinitrobenzene47in tartrate buffer when studied for its determination over the concentration ranges 2–50 and 0–125 µg ml–1of ascorbic acid respectively. Methanolic solution of resorcinol48gives a pale yellow color (λmax=425 nm) with ascorbic acid in hydrochloric acid medium, obeying Beer’s law for 80–400 µg ml–1. 4-Chloro-7-nitrobenzofurazane49forms a bluish green colored species with ascorbic acid in presence of 0.2 M sodium hydroxide. The absorbance is measured at 582 nm after diluting the reaction contents with 50% (v/v) aqueous acetone solution. Beer’s law is obeyed in the concentration range 5–20 µg ml–1. The colored prod-uct is stable for 30 min only when kept away from direct sunlight or artificial day light. The method is reported free from the interference of all other vitamins and minerals present in multivitamin preparations and can be applied to the analysis of pharmaceuticals, fresh fruit juices and vegetables.Hashmi et al.50proposed a method based on the reac-tion of 2,3,5-triphenyltetrazolium chloride with ascor-bic acid in alkaline medium. The pink solution is allowed to stand in the dark for 30 min at 25˚C; it obeys Beer’s law over the range 5–25 µg ml–1. Sugars (>15 µg ml–1) except sucrose interfere by forming a similar color to that of the reagent. Riboflavin, cyanocobalamin and folic acid interfere due to their own color. Beutler et al.51,52investigated the use of methylthiazolyltetrazolium salt in presence of ascorbate oxidase enzyme and 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium chloride or bromide in the pres-ence of 5-methylphenazinium methyl sulfate (electron carrier) at pH 3.5 for the determination of ascorbic acid in foods, fruit juices and vegetables juices. These reac-tions involve the formation of formazon (λmax=578 nm). The interference of sulfur dioxide requires treat-ment with formaldehyde, and color interference from dark juices is removed by decolorization with 1% polyvinylpolypyrrolidone before filtration. Sorbitol, alcohol and oxalate interfere with the ascorbic acid oxi-dase. However, the effect of oxalate can be checked by adding a slight excess of Ca(II) ions. Other derivatives such as 2,5-diphenyl-3-thiazolyl tetrazolium chloride53 at pH 12.2, 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium chloride at pH 10.5 (λmax=540 nm) and 2,2′,5,5′-tetra-(4-nitrophenyl)-3,3′-(3,3′-dimethoxy-4,4′-biphenyl)ditetrazolium chloride54have also been employed for the assay of ascorbic acid.The coupling of 2,4-dinitrophenylhydrazine (DNPH) with ketonic groups of DHAA and diketogulonic acid (DKGA) has been the basis of many methods for the determination of total vitamin C contents. Proteins present in the samples are precipitated by adding trichloroacetic acid (TCA) and aliquots of filtrate are shaken with acid–washed charcoal (norit) or activated charcoal55to clarify the solutions and to oxidize AA to DHAA. A reducing medium is produced by adding thiourea prior to DNPH addition, otherwise unspecific coloration is given by oxidants. The osazones (λmax=545 nm) thus formed during the 3 h incubation at 37˚C by the reaction of DNPH and DHAA are dis-solved by adding 85% H2SO4. Vitamin C can be extracted with metaphosphoric acid–stannous chloride solution without charcoal treatment for differential determination of DKGA, DHAA and AA in the same tissue extracts. The interference of sugars can be mini-mized by carrying out incubation at 15˚C and measur-ing the absorbance only after adding sulfuric acid for 75 min.56The use of several acid mixtures has been proposed for replacing the tedious dropwise addition of sulfuric acid. Lack of specificity is found with many of these methods; interfering osazones can be separated by chromatographic methods such as TLC57and HPLC58, but at the cost of making these procedures tedious and cumbersome. The nature of DNPH meth-ods for total vitamin C also makes it amenable to auto-matic flow through analyses.59–61 Phenylhydrazinium chloride62produces a yellow color (λmax=395 nm) when treated with ascorbic acid in0.1 M HCl medium. The reaction contents are kept for1 h in an incubator or water bath at 50±2˚C, thus mak-ing the method time-consuming. Beer’s law is obeyed in the range 25–100 µg of ascorbic acid. No interfer-ence is observed from other vitamins, minerals, glucose, sucrose, excipients and reducing agents. However, the presence of excessive amounts of riboflavin requires the addition of 0.5 g talc, which imparts a yellow color to the solution. 3-Methyl-2-benzothiazolone hydrazone63reacts in the presence of sodium metaperiodate to form a blue colored solution (λmax=630 nm) which helps in the determination of ascorbic acid over the range 6–14 meq ml–1.Wang64suggested the use of potassium iodate for the determination of vitamin C in pharmaceuticals. The absorbance is measured either in the UV region (288 nm) or in the visible region (445 nm). Besides aqueous phase measurements, the yellow precipitate can be extracted into chloroform65(λmax=514 nm). The ICl2–generated in the oxidation of AA by iodate66in acid medium in the presence of Cl–ions has been used to iodinate 2′,7′-dichlorofluorescein dye. The iodinated dye (λmax=525 nm) obeys Beer’s law up to 300 µg (ε=8.81×103). Soft drinks67have been analyzed using the reaction of iodine in an acetic acid medium (λmax= 350 nm). Sirividya and Balasubramanian68reported an indirect procedure based on the oxidation of ascorbic acid by a known excess of iodate in the presence of acid for the analysis of pharmaceuticals and fresh fruit juices. The unreacted iodate is used for hydroxylamine oxidation to generate nitrite, which is then diazotized with sulfanilic acid. The resulting diazonium salt is coupled with N-(1-naphthyl)ethylenediamine dihy-drochloride to form an azo dye (λmax=540 nm). The procedure is a complicated one as it involves many steps.The reaction of hexacyanoferrate(III)69(5)was used for the determination of micro quantities of vitamin C by measuring the decrease in color intensity of the reagent (5)(λmax=420 nm) in McIlvaine buffer (pH 5.2)solutions. Beer’s law is restricted within the range 180–270 µg of AA. A 200-fold amount of glucose, urea,citric acid and tartaric acid; 50-fold excess of creatineand 2-fold excess of creatinine do not interfere, but apositive error is observed even with very small quanti-ties of uric acid. In general, all such reagents thatreduce hexacyanoferrate(III) or oxidize hexacyanofer-rate(II) under experimental conditions interfere.Further the utility of the method is limited to colorlesssolutions. Yet another method involving the oxidationof phthalophenone to phenolphthalein by the reagent(5)in alkaline solution was proposed by Al-Tamrah.70This obeys Beer’s law up to 7 µg ml–1(λmax=553 nm). Sugars are tolerated only in microgram amounts. Therelative standard deviation and detection limit are0.65% and 0.1 µg ml–1respectively.Direct UV spectrophotometry71–73with backgroundcorrection methods such as thermal decomposition, UVlight irradiation, catalytic destruction and alkaline treat-ment has been used for the determination of AA in softdrinks, fruit juices and pharmaceuticals. However, therate of thermal decomposition is found to be very low72and fruit juice samples that are unstable to alkalinetreatment, have fine particles, have a deep coloration orcontain high concentrations of caffeine, saccharin,caramel and tannic acid can not be analyzed. Somemethods based on the Cu(II)-catalyzed oxidation arereported for the assay of pharmaceuticals, fruits andbeverages74–77allowing the determination of AA up to120 µg ml–1at λmax=267 nm. Fe(II) interferes seriously. Only minute amounts of folic acid are tolerated. Thepresence of Al(III), Mg(II) or Zn(II) gives a negativeerror due to their catalytic effect.Some methods involving the coinage metal (Cu, Ag,Au) complexes have been worked out. The reductionof Cu(II) in a biphasic system of isopentyl alcohol andan aqueous solution of pH 4.6 to Cu(I), followed by itscomplexation with cuproine to give a colored complex(λmax=454 nm), was reported by Contreras et al.78for the analysis of foods and vegetables. Fresh fruits andvegetables and dehydrated samples were analyzed afterextracting with 5% HPO3and with a 1:1 mixture of0.5% HPO3and 0.05 M H2SO4respectively. Also thecolored complexes of Cu(I) with 2,2-biquinoline79(λmax=540 nm), rhodanine80(λmax=473 nm) and 2,9-dimethyl-1,10-phenanthroline81–83(λmax=450 nm) have been used to determine ascorbic acid in different sam-ples. However, the method using 2,9-dimethyl-1,10-phenanthroline obeys Beer’s law over the range 2–20µg ml–1, though it requires 1 h waiting time for full color intensity. These methods based on the complex-ation of reduced Cu(I) are rather unselective, since sub-stances such as Fe(II), cysteine, or sodium thiosulfatewhich lead to the reduction of Cu(II) to Cu(I) interfereseriously. The gelatin complexes84,85of Ag(I)(λmax=415 nm; ε=2.2×103) and Au(III) (λmax=540 nm;ε=2.3×103) give colored products on adding AA to their alkaline solutions. The procedure as suggested by Pal et al.84is not interfered with by glycine, alanine, fruc-tose, sucrose, citric acid, tartaric acid or other reducingagents.Analytical applications of Molybdenum Blue formedon reduction of phosphomolybdate complex86, ammoni-um molybdate87–89or molybdic acid90have been report-ed by many workers for the determination of ascorbicacid in pharmaceuticals, fruits and vegetables, pastriesand beverages. Ammonium molybdate–sulfuric acidsystem requires 1 h for complete development of colorwith ascorbic acid.87However, such waiting time canbe decreased to 15 min by the addition of metaphos-phoric acid–acetic acid solution.88The colored speciesobeys Beer’s law over the range 2–32 µg ml–1at 760nm (ε=4.3×104). Serious interferences are observed due to phenolic compounds such as catechins, gallicacid, pyrogallol and gallotannins; thiosulfate ions andthiourea. Recently, P-Sb-Mo heteropoly acid91hasbeen used to produce heteropoly blue (λmax=710 nm) for the assay of ascorbic acid over the range 1–50 µgml–1(ε=3.68×103). The use of folin reagent92and folin phenol93(λmax=760 nm) has also been described for the assay of biological samples after deproteinizing withTCA. Beer’s law is obeyed up to 45 µg ml–1. Thecolor development is not obstructed by bovine serumalbumin, adenine, guanine, thymol and oxyhaemoglo-bin. Folin-ciocalteu94reagent reacts with ascorbic acidto give a blue colored complex (λmax=730 nm) as well. However, the method is time-consuming, as the fullcolor intensity requires 40–50 min. Ammonium meta-vanadate95gives a green color (λmax=680 nm) on heat-ing for 10 min in the presence of ascorbic acid.Though the method has been put to use for the analysisof some samples, it is not sufficiently sensitive.Many spectrophotometric methods based on thereduction of Fe(III) to Fe(II) with ascorbic acid, fol-lowed by the complexation of reduced Fe(II) with dif-ferent reagents, have been reported. Amongst them,α,α′-bipyridyl96–101and 1,10-phenanthroline102–109(o-phen) find extensive use in the development of analyti-cal procedures. Most of these methods are time-con-suming, as full color development is achieved onlyafter waiting for 30–60 min. Micromodification97ofthe procedure applicable to human plasma and animaltissue has been reported without the interference of glu-cose, fructose, sucrose, glutathione and cysteine.Recently, the procedure has been simplified by Aryaand Mahajan99so as to require only 5 min waiting time,instead of 30 or 60 min, with Beer’s law range up to 12µg ml–1(λmax=522 nm). Total ascorbic acid has been determined in blood plasma100after reducing DHAA with dithiothreitol at pH 6.5–8.0, removing the excess of dithiothreitol with N-ethylmaleimide and in urine101 by acidifying with TCA and shaking with activated chorcoal. The reduced Fe(II) forms a water-soluble colored complex with o-phenanthroline (λmax=510–515 nm) at pH 1.5–6.5, with obedience of Beer’s law up to 8 µg ml–1(ε=2.2×104). Background correction104 as achieved by Cu(II)-catalyzed oxidation is necessary for most samples, while the addition of NH4F106as theinhibitor of light reduction of Fe(III)-phen complex is needed in some cases. Selectivity for some of these methods is poor. However, an improvement using orange-red ferroin chelate in aqueous micellar medium formed in the presence of the cationic surfactant cetylpyridinium bromide109has been reported (ε=2.6×104at 510 nm). Ascorbic acid in fruits was determined after extracting the ternary complex of Fe(II) with α,α′-bipyridyl/o-phen and sulfophthalein110 dyes into chloroform (λmax=602 nm).Many other compounds including oximes111–113(6), 2-oximinocyclohexanone thiosemicarbazone114(2-OCHT) (7), 2-(5-bromo-2-pyridylazo)-5-dimethyl-aminophenol115(8)and 2-nitroso-5-(N-propyl-N-sulfo-propylamino)phenol116(9)have been investigated for their use in the analysis of pharmaceuticals and biologi-cal samples for ascorbic acid contents. The earlier reported extraction111of Fe(II)-dimethylglyoxime com-plex into chloroform, which allows the determination of 0.04–0.5 mM ascorbic acid, was modified by Arya et al.112They determined its concentration up to 14 µg ml–1at 514 nm. A proportionate decrease in color intensity of Fe(III)-resacetophenone oxime113complex in sodium acetate–acetic acid buffer (pH 5) with the increasing amounts of ascorbic acid was used for its assay in the range 3.5–17.5 µg (ε=4×103). The method using 2-OCHT determines ascorbic acid up to 12 µg ml–1(ε=1.49×104), but is interfered with by metal ions such as Cu(II), Co(II), Ni(II) and Pd(II), in addition to the interference caused by the oxalic acid, riboflavin, oxidants and reductants. Color-forming reactions of Fe(II) with ferrozine117–119(λmax=562 nm) in acidic solu-tions (pH 3–6), TPTZ120–122(λmax=593, 595 nm), quinaldic acid in presence of pyridine123(λmax=380 nm), picolinic acid in presence of pyridine124(λmax=400 nm) and nitroso-R salt125(λmax=705 nm) have been used for the determination of vitamin C in a variety of samples. The reagents picolinic acid and quinaldic acid, when complexed with iron(II) in the presence of pyridine, resulted in methods used successfully in the analysis of pharmaceuticals, food products and biologi-cal samples. The respective colored complexes getting extracted into chloroform obey Beer’s law in the range 0.4–5.6 µg ml–1and 2.5–25 µg ml–1ascorbic acid without the interference of common ingredients of the samples studied. Though the method using ferrozine117 is not interfered with by sucrose, glucose, mannose, fructose and formaldehyde, yet it suffers interferences from tartaric acid, citric acid, Co(II), Ni(II) and Fe(II). However, reactions of citric acid and tartaric acid can be masked by adding Al(III) or La(III) ions and that of iron(II) by passing the solution through a cation exchanger.Most of the reported methods based on the reducing action of ascorbic acid on metal ions invariably make use of an iron(III)–iron(II) redox system. A few use copper(II)–copper(I), vanadium(V)–vanadium(IV) or molybdenum/tungsten blue formation reactions, as mentioned earlier in the text. Arya et al. have reported a new redox system involving Cr(VI)-diphenyl-carbazide complex126(λmax=540 nm), which obeys Beer’s law up to 3.2 µg ml–1. Common additives of pharmaceutical preparations have no adverse effect on the absorbance of the complex. Another fast and facile method based on the proportionate decrease in absorbance of iron(III)-ferronate complex127(λmax=465 nm) by the addition of ascorbic acid was proposed by the same authors after extracting the complex into TBA/CHCl3solution. Beer’s law is valid up to 10 µg ml–1.3 ConclusionEven after the introduction of other instrument-based procedures, photometric methods continue to be of interest because of the ease in accessibility and their quick applicability to the routine analyses. The molar absorptivity for most of the colored species used in col-orimetric analysis of vitamin C lies over the range 103 to 1041 mol–1cm–1at the wavelength of maximum absorbance. This enables the precise determination of vitamin C in a variety of samples. The presence of cer-tain substances, especially the matrix constituents, may cause serious interferences. However, attempts to over-come such interferences either by using masking agents or making preliminary separations are invariably tried, but sometimes without much success, thus resulting in methods of varying selectivity. It has not been possible to categorize the methods based on the selectivity since the relevant data is found to be missing in the summary part of most methods reported in Chemical Abstracts. But none of the methods is found entirely specific for vitamin C. Despite the reporting of several new photo-metric methods, old procedures still continue to be cited in different pharmacopoeias, indicating either the lack of reliability or of general applicability of these methods of vitamin C determination. Research workers try to justify their work in terms of specific applica-tions, but seldom give an comparative account with other methods regarding analysis of particular type of matrix. Therefore, to incorporate the comparative use of such methods under specific analytical environment requires some patience.The authors wish to thank the Chairman, Department of Chemistry, Kurukshetra University, Kurukshetra, for necessary library facilities and Dr. Meenakshi Mahajan is grateful to CSIR for financial assistance.4 References1.H. Nie and S. Peng, Yingyang Xuebao, 6, 293 (1984).2.X. Shao and Y. Zhang, Guangpuxue Yu Guangpu Fenxi,14, 125 (1994).3.K. Vamos, Elmelz Ip., 43, 16 (1989).4.H. P. Huang, R. X. Cai, Y. M. Du and Y. E. 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河南省第九届自然科学优秀学术论文评审结果汇总表(河南...

高世扬夏树屏杨林
4 6 3 3 3
都国安
郭奇勋
6 3
45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67
Synthesis and Characterization of an Unexpected Asymmetric Binuclear Copper(I) Complex Containing 4-Vinyl-pyridine Synthesis,Structure and Ionic Conductivity of La2/3-xLi3xMoO4 Interactions between 1-benzoyl-4-p-chlorophenyl thiosemicarbazide and serum albumin: investigation by fluorescence spectroscopy fluorescence spectroscopy studies on 5-aminosalicylic acid and zinc 5- aminosalylicylate interaction with human serum albumin Inhibitory Kinetic-Fluorimetric Determination of Trace Aniline Kinetic spectorphotometric determination of formaldehyde in fabric and air by sequential injection analysis Spectrofluorimetric determination of tannins based on their activative effect on the Cu(Ⅱ) catalytic oxidation of rhodamine 6G by hydrogen peroxide Study of the concentration and separation of cadmium with microcrystalline phenolphthalein modified by crystal violet Flotation Separation of Lead with Sodium Nitrate-Potassium Iodide-Cetyltrimethyl Ammonium Bromide System Determination of Formaldehyde Traces in Fabric and in Indoor Air by a Kinetic Fluorimetric Method Flow-Injection Spectrophotometric Determination of Sulfadiazine and Sulfamethoxazole in Pharmaceuticals and Urine Determination of Trace Metoclopramide by Anodic strippingVoltammetry with Nafion Modified Glassy Carbon Electrode A Novel Poly(4-Aminopyridine)-Modified Electrode For Selective Detection Of Uric Acid In The Presence Of Ascorbic Acid The Separation and Determination of Nitrophenol Isomers By High-Performance Capillary Zone Electrophoresis. An efficient method for the oxidation of aryl substituted semicarbazides to aryl azo compounds with NaNO2-Ac2O An efficient method for the synthesis of α,β－unsaturated acyl azo compounds with NaNO2/NaHSO4H2O/SiO2 An ionic liquid as a recyclable medium for the green preparation of α,α'-bis (substituted benzylidene) cycloalkanones catalyzed by FeCl36H2O An efficient and green procedure for the preparation of acylals from aldehydes catalyzed by Fe2(SO4)3xH2O A Novel Preparation of 4-Phenylquinoline Derivatives in Ionic Liquids SmI2-mediated facile one-pot preparation of 2,4-diarylquinolines from 3-aryl-2,1-benzisoxazoles SmI2-mediated synthesis of 2,4-diarylpyrroles from phenacyl azides Preparation of dihomoallylic secondary amines through samarium mediated allylation of oximes SmI2 mediated synthesis of 2,3-disubstituted indole derivatives

药物代谢产物安全性评价指导原则

药物代谢产物安全原则解读—二〇一五年六月物安全性评价指导—实例解析年六月二十六日药物代谢产物安全性评价CFDA指导原则的内容及解实例介绍总结性评价指导原则近年发展容及解析药物代谢产物安全性评价FDA（2008）ICH（200December2009EMA/CPMP/ICH/286/1995ICH guideline M3(R2clinical safety studieconduct of human cand marketing authopharmaceuticals主要参考FDA的MIST指南，同时考虑了指导原则代表了药物代谢产物安全性研究性评价指导原则近年发展2009）CFDA（2012）M3(R2)on non-studies for theman clinical trialsauthorization for药物代谢产物安全性试验技术指导原则2009年6月药审中心组织翻译默克药业有限公司翻译2012年颁布虑了ICH M3中代谢产物安全性研究要求，本性研究的基本要求国内外指导原则主要内容比ICH FD关键点（Endpoint）Exposure Steady stat阈值标准（Threshold)>10%of totalexposure>10%of pare按照>10%定位Circulating Circulating（Localization）andexcretedonon a b内容比较FDA CFDAstate plasma AUC稳态时总体药物暴露量AUCparent drug（实际0%总暴露量执行）>药物总体暴露量的10%高比例循环代谢产物ng only(excreted onlycase by case basis),如果血液中无法测到，可考虑采用排泄物中暴露量进行验证适用范围背景信息决策图及说明评价代谢产物安全性一推荐的代谢产物安全性安全性研究的时间安排全性一般方法安全性实验间安排适用于小分子化学创新药不适用于那些需要考虑风险效抗肿瘤药的代谢产物参考晚期癌症患者治疗时，的毒理评价其他严重或危及生命疾病中风、HIV）的药物代谢产可根据具体情况具体分析的风险效益评价的药物物参考ICH S9指导原则，代谢产物并不要求必须开展单独命疾病的（如肌萎缩性侧索硬化ALS、代谢产物的非临床实验数量和类型分析的原则进行调整•化学反应性•药理学活性•可能与靶点受I相代谢产物增加水溶性，•潜在毒性化合物代谢产物•半衰期短，•形成可检测稳醚氨酸等结合产活性中间体▪人体中形成的代谢产物仅在人体▪常见的情况是，人体形成的代谢性试验中代谢产物的比例水平点受体或其他受体结合，引起非预期的效应，失去药理学活性（不需要安全性评价）化合物（如乙酰葡萄糖醛酸；可能需要安全性评价）可能更需要安全性评价，难以检测检测稳定产物（谷胱甘肽、甘氨酸、半胱氨酸、硫结合产物）不需要安全性评价在人体中存在而不在动物种属存在，出现的几率极低的代谢产物比例水平远远高于母体药物在动物安全高比例药物代谢产总体药物系统暴露量在动不能否(AUC)的10%无需进一步安全性试验评价代谢产物进行代谢产物的非临床试验代谢产物>总体药物系统暴露量(AUC)的10%14C标记药物人体药代实验在动物试验中的暴露量不能达到人体暴露量是否会在一种动物种属中形成？是,形成多少？在动物试验中的暴露量能达到人体暴露量不需要进一步的代谢产物的非临床试验人体14C-AME研究获得的数据为当高比例药物代谢产物确定后到稳态时血浆暴露量，主要基于性动力学因素考虑如果发现代谢产物的结构具有潜量，也需要进行进一步非临床安人体与动物暴露量的比较，通常况采用Cmax可能更合理代谢产物的绝对暴露量考虑数据为单次给药血浆暴露量的结果定后，需要定量其在人体多次给药达要基于重复给药后可能的蓄积和非线具有潜在的毒性，即使<10%血浆暴露临床安全性评价。

核磁共振法测定片剂中西咪替丁

核磁共振法测定片剂中西咪替丁张秀丽;王聪;王远红;吕志华【摘要】A method for the determination of cimetidine in tables by proton nuclear magnetic resonance spectroscopy (1H NMR) was established.The1H NMR spectra was obtained in MeOD withdimethyl terephthalate as the internal standard by using Agilent DD2–500 MHz spectrometer. For each sample,16 scans were recorded with the following parameters: pulse angle was 45°, relaxation delay was 20 s,acquisition time was 2 s, the temperature was set at 25℃. The linear range was 0.1–5.0 mg/mL with correlation coefficient of0.999 8. The relative standard deviation of detection results was 0.11%(n=6). The added average recoveries of cimetidine in tables were in the range of 100.03%–100.58%. The cimetidine samples from different factory were detected by the method and pharmacopoeia method, the results were consistent. This method is simple,rapid, with less cimetidine sample, it can be used for the quality control of cimetidine.%建立以核磁共振技术测定片剂中西咪替丁含量的方法。

药品与生活的英语作文

药品与生活的英语作文Title: The Intersection of Pharmaceuticals and Everyday Life。

In today's world, pharmaceuticals play a significant role in shaping our lives. From managing health conditions to enhancing quality of life, medications have become intertwined with our daily existence. In this essay, we'll explore the multifaceted relationship between pharmaceuticals and everyday life.First and foremost, pharmaceuticals are indispensablein maintaining and improving health. They serve as crucial tools in treating various illnesses, ranging from common colds to chronic conditions like diabetes and hypertension. Medications not only alleviate symptoms but also target the root causes of diseases, allowing individuals to lead healthier, more fulfilling lives. For instance, antibiotics combat bacterial infections, while insulin regulates blood sugar levels in diabetics. Without these pharmaceuticalinterventions, many individuals would struggle to manage their health effectively.Moreover, pharmaceuticals have expanded beyondtraditional treatments to encompass preventive care and wellness enhancement. Vaccines, for example, protectagainst infectious diseases by bolstering the body's immune response. Routine screenings and diagnostic testsfacilitated by pharmaceutical innovations enable early detection of conditions such as cancer and cardiovascular disease, leading to better outcomes through timely intervention. Additionally, nutritional supplements and lifestyle medications cater to individuals seeking to optimize their well-being, supporting efforts to maintain a balanced diet, manage stress, or improve cognitive function.In addition to their direct impact on health, pharmaceuticals influence societal norms and behaviors. The availability of contraception has empowered individuals to make informed choices about family planning, contributingto women's reproductive rights and gender equality. Psychotropic medications have destigmatized mental healthdisorders, prompting more open discussions and acceptance of conditions like depression and anxiety. Furthermore, pharmaceutical advertising and marketing shape consumer perceptions and preferences, driving demand for specific drugs and influencing healthcare-seeking behaviors.However, the pervasive presence of pharmaceuticals in everyday life is not without challenges. Concerns about overmedication and antibiotic resistance highlight the need for judicious prescribing practices and public education on the responsible use of medications. Access to affordable healthcare and essential medicines remains a pressing issue globally, exacerbating health disparities and hindering equitable health outcomes. Additionally, the pharmaceutical industry faces scrutiny over drug pricing, transparency, and ethical considerations surrounding clinical trials and marketing practices.Despite these challenges, pharmaceuticals continue to revolutionize healthcare and enhance quality of life for countless individuals worldwide. As science and technology advance, the future promises even greater innovations indrug discovery, personalized medicine, and holistic approaches to health and wellness. However, realizing the full potential of pharmaceuticals requires collaboration among stakeholders, including healthcare providers, policymakers, industry leaders, and the public, to ensure access, affordability, and ethical standards are upheld.In conclusion, pharmaceuticals are integral to modern life, shaping health outcomes, societal norms, and individual behaviors. While they offer tremendous benefits in treating illness and promoting well-being, they also pose challenges that must be addressed through concerted efforts. By recognizing the complexities of the pharmaceutical landscape and working together to navigate them responsibly, we can harness the power of medications to improve lives and build a healthier, more equitable future.。

药学英语书籍

药学英语书籍药学领域的英语书籍涵盖了药物科学的各个方面，包括药理学、药剂学、制药工艺学等。

下面是一些常见的药学英语书籍及其相关参考内容。

1. "Introduction to Pharmaceutical Calculations" by Judith A. Rees and Ian Smith:- Basic mathematics concepts and calculations required for pharmaceutical practice.- Dosage calculations, unit conversions, and dilution calculationsfor preparing medications.- Case studies and practice problems with solutions to reinforce learning.2. "Pharmaceutical Manufacturing Encyclopedia" edited byWilliam Andrew Publishing:- Comprehensive reference guide for pharmaceutical manufacturing processes.- Various manufacturing procedures, such as tablet compression, granulation, and parenteral preparations.- Information on different dosage forms, including tablets, capsules, creams, and injectables.- Quality control and regulatory aspects of pharmaceutical manufacturing.3. "Pharmacology and Pharmacotherapeutics" by R. S. Satoskar, Nirmala N. Rege, and S. D. Bhandarkar:- Principles of pharmacology and the therapeutic use of drugs.- Mechanisms of drug action, pharmacokinetics, andpharmacodynamics.- Drug interactions, adverse effects, and drug utilization in special populations.- Clinical applications of drugs in various diseases and conditions.4. "Pharmaceutical Analysis: A Textbook for Pharmacy Students and Pharmaceutical Chemists" by David G. Watson:- Analytical techniques used in pharmaceutical analysis.- Qualitative and quantitative analysis of drugs and pharmaceuticals.- Spectroscopic methods, chromatography, and separation techniques.- Validation and quality assurance of analytical methods.5. "Remington: The Science and Practice of Pharmacy" edited by David B. Troy and Joseph Price Remington:- Comprehensive resource on pharmacy practice and pharmaceutical sciences.- Topics ranging from pharmaceutical chemistry to pharmacy administration.- Drug discovery, formulation development, pharmacokinetics, and drug delivery systems.- Pharmaceutical calculations, compounding, and pharmacy laws and ethics.6. "Medicinal Chemistry: The Modern Drug Discovery Process"by Erland Stevens and Wei-Cheng Wang:- Introduction to medicinal chemistry and drug discovery.- Structure-activity relationships (SAR) and drug design.- Drug metabolism, pharmacokinetics, and drug targeting strategies.- Case studies of successful drug discovery and development.这些药学英语书籍提供了广泛而深入的知识，以帮助药学专业人员和学生在药物科学领域取得成功。

有关于马的英语美文阅读

有关于马的英语美文阅读马匹紧闭着嘴通过鼻子呼气，但不会发出像喷鼻息那样的振动或扑动样的噪音。

小编精心收集了有关于马的英语美文，供大家欣赏学习!有关于马的英语美文篇1Ma is a hard-working, lovely and good animal horse there are many colors, brown, maroon, white, black ...... horses, a pair of bells like eyes, always stares at somewhere. Horse, sleeping posture and people are different, who are lying in bed, while horse? It is not so much sleep, than it is in the "stop sleep." Because horses sleep standing up sleep. Marco's father - that is, the Broncos, formerly living in the forests or grasslands, wild animals have been attacked at any time, so they sleep standing up, in order to hear the movement ten to quickly escape, although now there is no beast domesticated horses to attack, but stood sleeping habits did not vanish, so horses always sleep standing up. So my favorite horse.马是勤劳的、可爱的、好动物马有很多颜色,棕色、栗色,白人,黑人……马,一对铃铛一样的眼睛,总是盯着某个地方。

药学专业的英文书

药学专业的英文书Pharmaceutical Studies: An English Book for Pharmacy MajorsIntroductionPharmaceutical studies play a vital role in the healthcare industry by ensuring the safe and effective use of medications. As the world becomes increasingly interconnected, it is essential for pharmacy professionals to possess strong English language skills to effectively communicate and collaborate with international counterparts. This book aims to provide a comprehensive guide for pharmacy majors, enhancing their English language proficiency within the pharmaceutical context.Chapter 1: Foundations of Pharmaceutical English1.1 Introduction to Pharmaceutical English- Definition and importance of Pharmaceutical English- Overview of its applications in different areas of pharmacy1.2 Pharmaceutical Terminology- Key pharmaceutical terms and expressions- Understanding drug names, classifications, and dosages1.3 Reading and Comprehension Skills- Strategies for understanding pharmaceutical literature- Interpreting drug labels, instructions, and patient information leafletsChapter 2: Pharmaceutical Communication Skills2.1 Effective Verbal Communication- Developing confident oral communication skills- Tips for successful patient counseling and medical consultations2.2 Written Communication in Pharmacy- Writing accurate prescription instructions and medication orders- Crafting professional, concise, and error-free pharmaceutical reports2.3 Effective Teamwork and Collaboration- Collaborating with healthcare professionals, including physicians and nurses- Resolving communication barriers and preventing medication errorsChapter 3: Pharmacology and Therapeutics3.1 Overview of Pharmacology- Understanding drug action and mechanisms- Classification of medications based on therapeutic effects3.2 Common Drug Interactions- Recognizing and managing potential drug interactions- Pharmacokinetic and pharmacodynamic interactions explained3.3 Rational Drug Use- Promoting evidence-based prescribing practices- Encouraging responsible patient medication adherenceChapter 4: Pharmaceutical Care and Patient Counseling4.1 Pharmaceutical Care Concepts- Introduction to patient-centered care- The role of pharmacists in optimizing medication therapy outcomes 4.2 Patient Counseling Techniques- Communication skills for patient education- Addressing patient concerns, side effects, and drug allergies4.3 Cultural Competence in Pharmacy- Recognizing and respecting diverse patient backgrounds- Adapting communication to meet cultural and linguistic needs Chapter 5: Regulatory and Ethical Considerations in Pharmacy5.1 Pharmaceutical Regulations- Overview of drug regulation authorities- Understanding drug registration and approval processes5.2 Professional Ethics in Pharmacy- Ethical guidelines for pharmacy professionals- Ensuring patient confidentiality, privacy, and informed consent 5.3 Drug Safety and ADR Reporting- Recognizing adverse drug reactions (ADRs)- Proper documentation and reporting procedures for ADRsConclusionMastering English language skills within the pharmaceutical context is crucial for success in the contemporary healthcare landscape. This English book for pharmacy majors provides comprehensive guidance and knowledge, equipping students and professionals with the necessary language proficiency to excel in their careers. By enhancing communication skills and promoting patient-centered care, pharmacy professionals can contribute significantly to the safe and effective use of medications globally.。

《中国药典》2020 年版四部 通则 英文

抗病毒药物达菲

药品英语作文

苯磺酸氨氯地平片英文说明书

pharmaceutics英文解释

苯磺酸氨氯地平片英文说明书

四环素类抗生素生物降解研究进展

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