富马酸替诺福韦杂质列表
富马酸丙酚替诺福韦 结构式
富马酸丙酚替诺福韦结构式富马酸丙酚替诺福韦的结构式如下：富马酸丙酚替诺福韦是一种抗病毒药物，其化学名称为（S）-2-（（S）-2-{[(S)-1-（（2-氨基-9H-嘧啶-6-基）甲基）-2-恶唑基]（甲基）氨基}-3-羟基丙酸（2R，3S）-2-乙酯。
这种药物主要用于治疗乙型肝炎病毒感染。
富马酸丙酚替诺福韦的结构式中展示了药物分子的结构组成和空间排列。
富马酸丙酚替诺福韦由多个功能基团组成，包括嘧啶环、恶唑环、甲基氨基和羟基丙酸基团。
这些功能基团在药物分子中有着特定的位置和排列，与药物的抗病毒活性密切相关。
富马酸丙酚替诺福韦的嘧啶环是药物分子的核心结构，具有抗病毒活性的关键作用。
嘧啶环上的氨基和甲基氨基团通过形成氢键与病毒RNA的碱基配对结合，从而抑制病毒复制。
恶唑环则通过与病毒酶结合抑制其活性，进一步阻断病毒复制过程。
富马酸丙酚替诺福韦的羟基丙酸基团也具有重要的作用。
羟基丙酸基团通过与病毒RNA或酶结合，调节药物与病毒之间的相互作用，增强抗病毒效果。
富马酸丙酚替诺福韦的结构式不仅展示了药物分子的结构组成，还提供了药物分子空间结构的信息。
药物分子的空间结构对于其与病毒靶点的相互作用至关重要。
药物的空间结构决定了其在生物体内的吸收、分布、代谢和排泄等性质，进而影响其药效和安全性。
富马酸丙酚替诺福韦的结构式为研究人员提供了一个重要的参考，可以通过对其结构的分析和优化，设计出更具高效和安全性的抗病毒药物。
同时，富马酸丙酚替诺福韦的结构式也为医生和药师提供了理解和解释药物作用机制的基础，从而更好地指导药物的临床应用。
富马酸丙酚替诺福韦的结构式是理解和研究该药物的重要工具。
通过分析结构式，我们可以了解药物分子的结构组成和空间排列，进而理解其与病毒靶点之间的相互作用，为药物的研发和临床应用提供科学依据。
富马酸替诺福韦二吡呋酯片处方开发研究
富马酸替诺福韦二吡呋酯片处方开发研究目的对富马酸替诺福韦二吡呋酯片的处方进行筛选，提取出最佳的处方配伍方案。
方法参照国外上市片“VIREAD?”的处方工艺，对其稀释剂、崩解剂、粘合剂、润滑剂以及包衣工艺进行实验，并将自制样品与参比制剂在高温、高湿及光照条件下进行稳定性考察，筛选出合理的处方工艺。
结果最终确定处方工艺为：富马酸替诺福韦二吡呋酯300mg；乳糖60mg；微晶纤维素165mg；预胶化淀粉100mg；交联羧甲基纤维素钠35mg；硬脂酸镁5mg；欧巴代薄膜包衣预混剂20mg；以纯化水为粘合剂。
结论确定的处方工艺稳定，生产过程不苛刻，适合放大生产，稳定性研究结果与市售品性质相似，体外溶出行为相近，处方设计合理。
[Abstract] Objective To extract the best prescription compatibility program，the prescription of tenofovir disoproxil fumarate tablets were screened. Methods According to prescription techno logy of foreign sales “VIREAD?”，carried out experiments on its diluents，disintegrating agents，binders，lubricants and coating process，and homemade samples and reference preparation were stability studied under the conditions of high temperature，high humidity and illumination，screening a reasonable prescription process. Results Prescription process was ultimately determined including：tenofovir disoproxil fumarate 300mg；lactose 60mg；microcrystalline cellulose 165mg；pre-gelatinized starch 100mg；cross-linked sodium carboxymethyl cellulose 35mg；magnesium stearate 5mg；Opadry film coating premixes 20mg；purified water as a binder. Conclusion Prescription process determined is stable，production process is not harsh，suit amplification production，similar to the stability of the results and the nature of commercial products，similar behavior in vitro dissolution，the design of prescription is reasonable.[Key words] Tenofovir disoproxil fumarate tablets；Stability；Prescription process；Reference prepara tion “VIREAD?”富马酸替诺福韦二吡呋酯是替诺福韦的口服前体药物。
富马酸替诺福韦酯--------印度药典
NOTE - Prepare the solutions immediately before use. Test solution. Dissolve 100 mg of the substance under examination in 50 ml of methanol. Reference solution (a). A 0.2 per cent w/v solution of tenofovir disoproxil jitmarate RS in methanol. Reference solution (b). Dilute 1.0 ml ofreference solution (a) to 100.0 ml with methanol. Reference solution (c). Dissolve 10 mg ofthejUmaric acid in 50 ml of methanol.
TELMISARTAN TABLETS
IP 2010
Solvent mixture. 80 volumes of buffer solution prepared by diluting 5.0 ml of triethylamine to 2000ml with water and 20 volumes of methanol. Test solution. Weigh and powder 20 tablets. Disperse a quantity ofpowder containing about 100 mg ofTelmisartan in 100.0 ml ofsolvent mixture, sonicate for 45 minutes and filter. Reference solution. A 0.0005 per cent w/v solution of telmisartan RS in the solvent mixture.
反相高效液相色谱法测定富马酸替诺福韦二吡呋酯的有关物质
反相高效液相色谱法测定富马酸替诺福韦二吡呋酯的有关物质陶静;李红艳【摘要】建立反相高效液相色谱法测定富马酸替诺福韦二吡呋酯中的有关物质.色谱柱为Inertsil Phenyl-3,以0.05 mol/L醋酸铵缓冲液-乙腈(体积比为97∶3)为流动相A,以0.05 mol/L醋酸铵缓冲液-乙腈(体积比为40∶60)为流动相B,梯度洗脱,检测波长260 nm.测定结果表明,该法可有效分离主药及降解产物,分离度达到1.5以上,破坏性试验主峰纯度的纯度因子均大于阈值980,可见峰纯度良好.该方法用来测定富马酸替诺福韦二吡呋酯中的有关物质结果准确、可靠.【期刊名称】《淮海工学院学报（自然科学版）》【年(卷),期】2012(021)004【总页数】3页(P60-62)【关键词】富马酸替诺福韦二吡呋酯;有关物质;高效液相色谱法【作者】陶静;李红艳【作者单位】南京耀恒医药科技有限公司,江苏南京210013;南京耀恒医药科技有限公司,江苏南京210013【正文语种】中文【中图分类】O657.70 引言富马酸替诺福韦二吡呋酯是新型核苷酸逆转录酶抑制剂，临床主要用于治疗人类免疫缺陷病毒（HIV）感染，同时通过干扰乙肝病毒DNA聚合酶的功能抑制乙肝病毒的复制，降低血清及肝组织内的病毒载量［1］。
2001年10月29日经美国FDA批准以商品名Viread在美国首次上市，用于治疗艾滋病；2008年4月和8月，欧盟和美国FDA根据大量的临床试验结果，又批准其用于治疗乙肝；目前富马酸替诺福韦二吡呋酯被专家和媒体誉为最好的抗乙肝药物之一，同时也是多个治疗指南推荐使用的一线抗艾滋病药物。
目前国内介绍富马酸替诺福韦二吡呋酯中有关物质测定方法的文章很少，或方法复杂，分离度差［2－4］。
本文建立了新的HPLC方法，使用该方法能够有效地分离主药及降解产物，结果准确、可靠、快速，可以用于富马酸替诺福韦二吡呋酯原料药的杂质控制［5－6］。
1 仪器与试药SPD－M10AVP高效液相色谱仪（日本岛津），Sartorius BT－25S型电子分析天平（赛多利斯科学仪器有限公司）。
替诺福韦说明书
替诺福韦说明书【中文通用名】替诺福韦【别名】泰诺福韦，替诺福韦酯富马酸盐，富马酸替诺福韦酯Tenofovir，Tenolo-VirdisoproxilFumarate，Viread．TDF【英文TNN名】TenofovirDisoprox【药品性质】处方药【药品分类】外国最新药品->抗微生物新药【药理毒理】本品是一种新式核苷酸类逆转录酶克制剂。
以与核苷类逆转录酶克制剂近似的方法克制逆转录酶，进而拥有潜伏的抗HIV-1活性。
替诺福韦的活性成分替诺福韦双磷酸盐可经过直接竞争性地与天然脱氧核糖底物相联合而克制病毒聚合酶，及经过插人DNA中停止链。
【药代动力学】替诺福韦几乎不经胃肠道汲取，所以进行酯化、成盐，成为替诺福韦酯富马酸盐。
替诺福韦酯拥有水溶性，可被快速汲取并降解成活性物质替诺福韦，而后替诺福韦再转变成活性代谢产物替诺福韦双磷酸盐。
给药后1～2h内替诺福韦达血药峰值。
替诺福韦与食品服时生物利用度可增大概40％。
替诺福韦双磷酸盐的胞内半衰期约为10h，可1天给药1次。
因为该药不经CYP450酶系代谢，因此，由该酶惹起的与其余药物间互相作用的可能性很小。
该药主要经肾小球过滤和主动小管转运系统排泄，约70％～80％以原形经尿液排出体外。
【适应症】用于治疗HIV、HBV感染。
本品和其余逆转录酶克制剂适用于HIV-1感染、乙肝的治疗。
【用法用量】口服：每天1次，每次300mg,与食品同服。
【不良反响】1.浑身无力 2.胃肠道反响轻至中度的胃肠道不适，常有的有腹泻、腹痛、食欲减退、恶心、呕吐和胃肠胀气、胰腺炎。
3.代谢系统低磷酸盐血症（1%发生率）；脂肪积蓄和从头散布，包含向心性肥胖、水牛背、末梢消瘦、乳房增大、库兴综合征。
4.可能惹起乳酸中毒、与脂肪变性有关的肝肿大等。
5.神经系统头晕、头痛。
6.呼吸系统呼吸困难。
7.皮肤药疹。
【规格】300mg*30颗/瓶【生产厂商】：美国 Glead/印度Cipla排行榜。
国产替诺福韦说明书
【商品名】倍信富马酸替诺福韦二吡呋酯片【通用名】富马酸替诺福韦二吡呋酯片【英文名】Teno fovirDisoproxilFumarate Tablets【汉语拼音】FuMaSua nTiNuoFuWeiErBiFuZhiPia n【主要成份】本品主要成分为富马酸替诺福韦二吡呋酯，其化学名称为9-［（R）-2-［［双［［（异丙氧基羰基）氧基］甲氧基］氧膦基卜丙基］腺嘌呤富马酸盐（1:1）。
【性状】本品为淡蓝色杏仁状薄膜衣片，除去包衣显白色。
【适应症】HIV-1感染富马酸替诺福韦二吡呋酯适用于与其它抗逆转录病毒药物联用，治疗成人HIV-1感染。
使用富马酸替诺福韦二吡呋酯开始治疗HIV-1感染时，应考虑一下几点：富马酸替诺福韦二吡呋酯不应与含有替诺福韦的固定剂量复方制剂联用，包括：•依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯；•利匹韦林/恩曲他滨/富马酸替诺福韦二吡呋酯；•艾维雷韦/克比司特/恩曲他滨/富马酸替诺福韦二吡呋酯；•恩曲他滨替诺福韦。
【用法用量】HIV-1的治疗：剂量为每次300mg （—片），每日一次，口服，空腹或与食物同时服用。
成人肾功能损害患者使用剂量的调整在中至重度肾功能损害的受试者中给予富马酸替诺福韦二吡呋酯时，药物暴露显著增加（参见【药代动力学】）。
对基线肌酐清除率v 50mL/分钟的患者，应按照表1调整富马酸替诺福韦二吡呋酯的给药间期。
在此推荐的给药间期是根据在不同肾功能损害级别的非HIV和非HBV感染受试者，包括需要血液透析的晚间肾病的患者中单次给药的药代动力学数据模型得出。
在中度至重度肾功能损害的患者中，尚未对这些给药间期调整建议的安全性和疗效进行临床评价，因此在这些患者中应当密切监测对治疗的临床反应和肾功能（参见【注意事项】）。
对轻度肾功能损害（肌酐清除率50-80mL/分钟）的患者，无需调整剂量。
在这些患者中应定期监测计算出来的肌酐清除率和血清磷。
（参见【注意事项】）。
富马酸丙酚替诺福韦治疗慢性乙肝临床抗病毒的疗效分析
DOI：10.19368/ki.2096-1782.2023.14.089富马酸丙酚替诺福韦治疗慢性乙肝临床抗病毒的疗效分析陈燕霞，黎坚健，邝德志台山市人民医院感染内科，广东台山529200[摘要]目的分析富马酸丙酚替诺福韦治疗慢性乙型病毒性肝炎的临床抗病毒疗效。
方法选取2020年1月—2022年1月台山市人民医院收治的90例慢性乙肝患者为研究对象，依据随机数表法分为两组，每组45例。
对照组接受常规药物（恩替卡韦分散片）治疗，研究组采用富马酸丙酚替诺福韦治疗。
比较两组治疗总有效率、治疗前后肝功能指标变化情况[天冬氨酸转氨酶（aspartate transaminase, AST）、丙氨酸转氨酶（alanine transaminase, ALT）、总胆红素（total bilirubin, TBIL）]、乙肝病毒基因（hepatitis B deoxyribonucleic acid, HBV-DNA）阴转率及不良反应发生情况。
结果研究组治疗总有效率与对照组相比更高（97.78% vs 80.00%），差异有统计学意义（χ2=7.200，P=0.007）。
治疗后，研究组丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素水平均低于对照组，差异有统计学意义（P<0.05）。
治疗后，研究组HBV-DNA阴转率（77.78%）高于对照组（51.11%），差异有统计学意义（χ2=6.983，P=0.008）。
两组不良反应发生率比较，差异无统计学意义（P>0.05）。
结论富马酸丙酚替诺福韦治疗慢性乙肝临床抗病毒疗效理想，可有效抑制抑制HBV病毒复制且用药安全具有保障。
[关键词]富马酸丙酚替诺福韦；慢性乙肝；抗病毒；恩替卡韦分散片[中图分类号]R4 [文献标识码]A [文章编号]2096-1782（2023）07(b)-0089-04Analysis of the Clinical Antiviral Efficacy of Tenofovir Alafenamide Fuma⁃rate in the Treatment of Chronic Hepatitis BCHEN Yanxia, LI Jianjian, KUANG DezhiDepartment of Infectious Diseases, Taishan People's Hospital, Taishan, Guangdong Province, 529200 China[Abstract] Objective To analyze the clinical antiviral efficacy of tenofovir alafenamide fumarate in the treatment of chronic hepatitis B virus. Methods Ninety patients with chronic hepatitis B treated in Taishan People's Hospital from January 2020 to January 2022 were selected as the study objects and divided into two groups according to random number table method, with 45 cases in each group. The control group was treated with conventional drugs (Entecavir dispersive tablets) and the study group was treated with profol tenofovir fumarate. The total effective rate, changes of liver function indexes [aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, aspartate transami‐nase (AST), alanine transaminase (Alt), and total bilirubin, respectively (TBIL)], before and after treatment hepatitis B deoxyribonucleic acid (HBV-DNA) negative conversion rate and adverse reactions were compared between the two groups. Results The total effective rate of the study group was higher than that of the control group (97.78% vs 80.00%), and the difference was statistically significant (χ2=7.200, P=0.007). After treatment, the levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin in the study group were lower than those in the control group, and the difference was statistically significant (P<0.05). After treatment, the negative conversion rate of HBV-DNA in the study group (77.78%) was higher than that in the control group (51.11%), and the difference was statisti‐cally significant (χ2=6.983, P=0.008). There was no statistically significant difference in the incidence of adverse reac‐tions between the two groups (P>0.05). Conclusion Propofol tenofovir fumarate has an ideal clinical antiviral effect in the treatment of chronic hepatitis B, which can effectively inhibit the replication of HBV virus and ensure the safety of [作者简介] 陈燕霞（1987-），女，本科，主治医师，研究方向为临床医学。
国产替诺福韦说明书
【商品名】倍信富马酸替诺福韦二吡呋酯片【通用名】富马酸替诺福韦二吡呋酯片【英文名】Tenofovir Disoproxil Fumarate Tablets【汉语拼音】FuMaSuanTiNuoFuWeiErBiFuZhiPian【主要成份】本品主要成分为富马酸替诺福韦二吡呋酯，其化学名称为9-[（R）-2-[[双[[（异丙氧基羰基）氧基]甲氧基]氧膦基]-丙基]腺嘌呤富马酸盐（1:1）。
【性状】本品为淡蓝色杏仁状薄膜衣片，除去包衣显白色。
【适应症】HIV-1感染富马酸替诺福韦二吡呋酯适用于与其它抗逆转录病毒药物联用，治疗成人HIV-1感染。
使用富马酸替诺福韦二吡呋酯开始治疗HIV-1感染时，应考虑一下几点：富马酸替诺福韦二吡呋酯不应与含有替诺福韦的固定剂量复方制剂联用，包括：·依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯；·利匹韦林/恩曲他滨/富马酸替诺福韦二吡呋酯；·艾维雷韦/克比司特/恩曲他滨/富马酸替诺福韦二吡呋酯；·恩曲他滨替诺福韦。
【用法用量】HIV-1的治疗：剂量为每次300mg（一片），每日一次，口服，空腹或与食物同时服用。
成人肾功能损害患者使用剂量的调整在中至重度肾功能损害的受试者中给予富马酸替诺福韦二吡呋酯时，药物暴露显著增加（参见【药代动力学】）。
对基线肌酐清除率＜50mL/分钟的患者，应按照表1调整富马酸替诺福韦二吡呋酯的给药间期。
在此推荐的给药间期是根据在不同肾功能损害级别的非HIV和非HBV感染受试者，包括需要血液透析的晚间肾病的患者中单次给药的药代动力学数据模型得出。
在中度至重度肾功能损害的患者中，尚未对这些给药间期调整建议的安全性和疗效进行临床评价，因此在这些患者中应当密切监测对治疗的临床反应和肾功能（参见【注意事项】）。
对轻度肾功能损害（肌酐清除率50-80mL/分钟）的患者，无需调整剂量。
在这些患者中应定期监测计算出来的肌酐清除率和血清磷。
WHO-富马酸替诺福韦Tenofovir disoproxil fumarate质量标准
Monographs: Pharmaceutical substances: Tenofoviri disoproxili fumaras - Tenofovir disoproxil fumarateC19H30N5O10P,C4H4O4Relative molecular mass. 635.5Chemical name. 1,1'-bis(1-methylethyl)1,1'-[({[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}phosphonoyldioxy)dimet hyl] dicarbonate (ester) hydrogen (2E)-but-2-enedioate (salt); CAS Reg.No. 202138-50-9.Description. White to almost-white, crystalline powder.Solubility. Slightly soluble in water, soluble in methanol, very slightly soluble in dichloromethane.Category. Antiretroviral (Nucleotide Reverse Transcriptase Inhibitor).Storage. Tenofovir disoproxil fumarate should be kept in a tightly closed container, protected from light, and stored at a temperature between 2 and 8°C.Additional information. Tenofovir disoproxil fumarate may exhibit polymorphism.RequirementsDefinition. Tenofovir disoproxil fumarate contains not less than 98.5 percent and not more than 101.0 percent of tenofovir disoproxil fumarate (C19H30N5O10P,C4H4O4), calculated with reference to the anhydrous substance.Manufacture. The production method is validated to ensure that the substance, if tested, would comply with:- a limit of not more than 5 ppm for the mutagenic impurity9-(prop-1-enyl)-9H-purin-6-amine (impurity K), which may be a synthesis related substance, using a suitable method, and- a limit of not more than 1.0% for the tenofovir disoproxil (S)-enantiomer (impurity G), using a suitable chiral chromatographic method.Identity tests• Either tests A, B and C or test D may be applied.A. Carry out test A.1 or, where UV detection is not available, test A.2.A.1 Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R6 as the coating substance and a mixture of 67 volumes of dichloromethane R, 20 volumes of acetonitrile R, 10 volumes of methanol R and 3 volumes of ammonia (~260 g/l) TS as the mobile phase. Apply separately to the plate 5 μl of each of 2 solutions in methanol containing (A) 10 mg of the test substance per ml and (B) 10 mg of tenofovir disoproxil fumarate RS per ml. After removing the plate from the chromatographic chamber, allow it to dry exhaustively in air or in a current of air. Examine the chromatogram in ultraviolet light (254 nm).The principal spot obtained with solution A corresponds in position, appearance, and intensity with that obtained with solution B.A.2 Carry out the test as described under 1.14.1 Thin-layer chromatography, using the conditions described above under test A.1 but using silica gel R5 as the coating substance. Stain the plate with iodine vapour and examine the chromatogram in daylight.The principal spot obtained with solution A corresponds in position, appearance, and intensity with that obtained with solution B.B. Carry out test B.1 or, where UV detection is not available, test B.2.B.1 Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R6 as the coating substance and a mixture of 50 volumes of heptane R, 30 volumes of glacial acetic acid R and 20 volumes of dichloromethane R as the mobile phase. Apply separately to the plate 5 μl of each of the following 2 solutions in ethanol R. For solution (A) use 10 mg of the test substance per ml and for solution (B) use 2 mg of fumaric acid R per ml. Develop the plate in an unsaturated tank over a path of 10 cm. After removing the plate from the chromatographic chamber, allow it to dry exhaustively in air or in a current of air. Examine the chromatogram in ultraviolet light (254 nm).One of the principal spots obtained with solution A corresponds in position, appearance, and intensity with that obtained with solution B.B.2 Carry out the test as described under 1.14.1 Thin-layer chromatography, using the conditions described above under test B.1 but using silica gel R5 as the coating substance. Spray lightly with a 16 g/l solution of potassium permanganate R and examine the chromatogram in daylight.The principal spot obtained with solution A corresponds in position, appearance, and intensity with that obtained with solution B.C. The absorption spectrum (1.6) of a 25 µg/ml solution, when observed between 220 nmand 320 nm, exhibits a maximum at about 261 nm; the specific absorbance () is 230 to 250.D. Carry out the examination as described under 1.7 Spectrophotometry in the infrared region. The infrared absorption spectrum is concordant with the spectrum obtained from tenofovir disoproxil fumarate RS or with the reference spectrum of tenofovir disoproxil fumarate. If the spectra thus obtained are not concordant, repeat the test using the residues obtained by separately dissolving the test substance and tenofovir disoproxil fumarate RS in a small amount of methanol R and evaporating to dryness. The infrared absorption spectrum is concordant with the spectrum obtained from tenofovir disoproxil fumarate RS.Specific optical rotation (1.4). Use a 10.0 mg/ml solution in hydrochloric acid (0.1 mol/l)VSand calculate with reference to the anhydrous substance; = -20° to -26°.Water. Determine as described under 2.8 Determination of water by the Karl Fischer method, Method A. Use about 1.0 g of the substance; the water content is not more than 10 mg/g.Heavy metals. Use 1.0 g in 30 ml of methanol R for the preparation of the test solution as described under 2.2.3 Limit test for heavy metals, Procedure 2; determine the heavy metals content accordi ng to Method A; not more than 20 μg/g.Sulfated ash (2.3). Not more than 1.0 mg/g.Related substances. Carry out the test as described under 1.14.4 High-performance liquid chromatography, using a stainless steel column (25 cm x 4.6 mm) packed withbase-deactivated particles of silica gel the surface of which has been modified with chemically bonded oct adecylsilyl groups (5 μm).The mobile phases for the gradient elution consist of a mixture of Mobile phase A and Mobile phase B, using the following conditions:Mobile phase A: 2 volumes of acetonitrile R, 20 volumes of phosphate buffer pH 6.0 and 78 volumes of water R.Mobile phase B: 65 volumes of acetonitrile R, 20 volumes of phosphate buffer pH 6.0 and 15 volumes of water R.Prepare the phosphate buffer pH 6.0 by dissolving 3.50 g of potassium dihydrogen phosphate R and 1.70 g of tetrabutyl ammonium hydrogen sulfate R in 800 ml of water R, adjust the pH to 6.0 by adding sodium hydroxide (1 mol/l) VS and dilute to 1000 ml with water R.After preparation, keep the solutions at about 6°C, or use an injector with cooling.Prepare the following solutions using water R as diluent. For solution (1) use 1.0 mg of the test substance per ml. For solution (2) dilute a suitable volume of solution (1) to obtain a concentration of 5 µg of tenofovir disoproxil fumarate per ml. For solution (3) use 0.2 mg of fumaric acid R per ml.For the system suitability test: prepare solution (4) by heating solution (1) carefully in a boiling water-bath for 20 minutes.Operate with a flow rate of 1.0 ml per minute. As a detector use an ultraviolet spectrophotometer set at a wavelength of 260 nm.Maintain the column temperature at 30 °C.Inject 20 μl of solution (4). The test is not valid unless the resolution between the principal peak (retention time about 40 minutes) and the peak due to the tenofovir monoester (with a relative retention of about 0.5) is not less than 25.Inject alternat ively 20 μl each of solutions (1) and (2) and (3). In the chromatogram obtained with solution (1), the following peak is eluted at the following relative retention, with reference to tenofovir (retention time about 40 minutes): fumarate about 0.15.In the chromatogram obtained with solution (1), the area of any peak due to the tenofovir monosoproxil (impurity A) is not greater than twice the area of the principal peak obtained with solution (2) (1.0%); the area of any other impurity peak is not greater than the area of the principal peak obtained with solution (2) (0.5%) and the areas of not more than two such peaks are greater than 0.4 times the area of the principal peak obtained with solution (2) (0.2%). The sum of the areas of all peaks, other than the principal peak, is not greater than 5 times the area of the principal peak obtained with solution (2) (2.5%). Disregard any peak corresponding to the peak obtained in the chromatogram with solution (3) and any peak with an area less than 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).AssayDissolve 0.40 g, accurately weighed, in 30 ml of glacial acetic acid R1 and titrate with perchloric acid (0.1 mol/l) VS, determine the end point potentiometrically as described under 2.6 Non-aqueous titration Method A. Each ml of perchloric acid (0.1 mol/l) VS is equivalent to 63.55 mg of tenofovir disoproxil fumarate (C19H30N5O10P,C4H4O4).ImpuritiesA. (1-methylethyl)(8R)-9-(6-amino-9H-purin-9-yl)-5-hydroxy-8-methyl-5-oxo-2,4,7-trioxa-5-λ5-phosphanon anoate (tenofovir monosoproxil),B. (1-methylethyl)(5RS,8R)-9-(6-amino-9H-purin-9-yl)-5-methoxy-8-methyl-5-oxo-2,4,7-trioxa-5-λ5-phosph anonanoate,B. methyl (1-methylethyl)(5RS)-5-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}-5-oxo-2,4,6,8-tetrao xa-5-λ5-phosphanonanedioate,D. (1-methylethyl)(5RS,8R)-9-(6-amino-9H-purin-9-yl)-8-methyl-5-(1-methylethoxy)-5-oxo-2,4,7-trioxa-5-λ5-phosphanonanoate,E. (1-methylethyl)(8R)-5-hydroxy-8-methyl-9-(6-{[(1-methylethoxy)carbonyl]amino}-9H-purin-9-yl)-5-oxo-2,4,7-trioxa-5-λ5-phosphanonanoate,F. bis(1-methylethyl)9,9'-[methylenebis(imino-9H-purine-6,9-diyl)]bis[(8R)-5-hydroxy-8-methyl-5-oxo-2,4,7-tri oxa-5-λ5-phosphanonanoate] (tenofovir monosoproxil dimer),G. bis(1-methylethyl)5-{[(1S)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}-5-oxo-2,4,6,8-tetraoxa-5-λ5 -phosphanonanedioate (tenofovir disoproxil (S)-enantiomer) [see under Manufacture],H. 1-methylethyl propyl(5RS)-5-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}-5-oxo-2,4,6,8-tetrao xa-5-λ5-phosphanonanedioate,I. bis(1-methylethyl)5-{[(1R)-2-(6-{[({9-[(2R)-5-hydroxy-2,11-dimethyl-5,9-dioxo-3,6,8,10-tetraoxa-5-λ5-pho sphadodecyl]-9H-purin-6-yl}amino)methyl]amino}-9H-purin-9-yl)-1-methylethoxy]methyl }-5-oxo-2,4,6,8-tetraoxa-5-λ5-phosphanonanedioate (tenofovir di- and monosoproxil heterodimer),J. tetrakis(1-methylethyl)5,5'-(methylenebis{imino-9H-purine-6,9-diyl[(2R)-propane-1,2-diyl]oxymethylene})bis[5-oxo-2,4,6,8-tetraoxa-5-λ5-phosphanonanedioate] (tenofovir disoproxil dimer),K. 9-(prop-1-enyl)-9H-purin-6-amine, [see under Manufacture],L. (1-methylethyl)(5RS)-5-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}-10-methyl-5,9-dioxo-2,4,6,8-tetraoxa-10-aza-5-λ5-phosphaundecanoate,M. ethyl 1-methylethyl(5RS)-5-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}-5-oxo-2,4,6,8-tetrao xa-5-λ5-phosphanonanedioate.。
富马酸替诺福韦二吡呋酯片(韦瑞德)的说明书
富马酸替诺福韦二吡呋酯片(韦瑞德)的说明书关于《富马酸替诺福韦二吡呋酯片(韦瑞德)的说明书》，是我们特意为大家整理的，希望对大家有所帮助。
内火旺止痛是普遍的一种病症，对日常生活和工作中影响很大，要是立即的服食药品开展医治就可以获得非常好的修复。
身心健康是与生活密切相关的，现阶段我们发布一款全名是富马酸替诺福韦二吡呋酯片(韦瑞德)的药品，它能合理协助您消除内火旺和止痛等病症，实际效果非常明显。
下列我们先讨论一下详细介绍。
生产药品名称疫苗通用性名字：富马酸替诺福韦二吡呋酯片产品名称：富马酸替诺福韦二吡呋酯片(韦瑞德)英文名字：Tenofovir disoproxil fumarate tablets拼音字母全码：FuMaSuanTiNuoFuWeiErBiFuZhiPian(WeiRuiDe) 生产关键成分疫苗富马酸替诺福韦二吡呋酯。
其有机化学名叫：9-((R)-2-((双(((异丙氧基羰基)氧基(甲氧基)氧膦基)-丙基)腺嘌呤富马酸盐（1:1）。
生产成份疫苗化学式：C19H30N5O10.C4H4O4相对分子质量：635.52生产性状疫苗本产品为乳白色甜杏仁状塑料薄膜糖衣片，一面上刻着GILEAD，下边刻着4331，去除薄膜包衣后显乳白色。
生产适用范围/功效与作用疫苗适用其他抗逆转录病毒药品共用，医治HIV-1感染。
生产型号规格疫苗300mg*30s生产使用方法使用量疫苗每天一次，每一次一片，内服，可空肚或与食材另外表明。
生产副作用疫苗二项科学研究中，本产品组近1/3的患者出現副作用，但这一发病率与对照实验类似。
本产品普遍的副作用包含：轻到轻中度的消化道不适感（普遍的有腹泻、恶心想吐、呕吐和肠胃胀气）；新陈代谢系统的低磷酸酶尿症（1％发病率）、血细胞聚磷酸盐轻到轻中度降低（科学研究中24周时本产品某组12％，对照实验为7％，58周时本产品某组15％）。
有产生乳酸菌性代谢性酸中毒的风险。
生产禁忌疫苗尚不确立。
LC-HRMS
[基金项目]广东省广州市知识产权工作专项资金（ZL201710649577.9）。
▲通讯作者LC-HRMS/MS研究富马酸替诺福韦二吡呋酯片中聚合物肖 颖1 王健松1▲ 袁 晓2 林顺权2 叶心睿31.广州白云山医药集团股份有限公司白云山制药总厂，广东广州 510515；2.广州牌牌生物科技有限公司，广东广州 510530；3.广州白云山明兴制药有限公司，广东广州 510250[摘要] 目的 研究富马酸替诺福韦二吡呋酯片中潜在的聚合物杂质。
方法 采用液质联用方法，选用大气压化学离子化源（APCI 离子源）和电喷雾离子化源（ESI 离子源）对富含杂质的样品（包括破坏实验后的样品）进行聚合物研究，发现其潜在的聚合物并推测其结构。
结果 富马酸替诺福韦二吡呋酯片破坏样品中检出二聚体、三聚体杂质。
结论 富马酸替诺福韦二吡呋酯片中存在潜在可检出的聚合物杂质：二聚体和三聚体杂质，其中二聚体的三个杂质为已知杂质，分别为杂质H、W、S。
[关键词] 富马酸替诺福韦二吡呋酯；二聚体；三聚体；液质联用[中图分类号] R969 [文献标识码] A [文章编号] 2095-0616（2024）07-0068-05DOI:10.20116/j.issn2095-0616.2024.07.16LC-HRMS/MS study on polymers in tenofovir disoproxil fumarate tabletsXIAO Ying 1 WANG Jiansong 1 YUAN Xiao 2 LIN Shunquan 2 YE Xinrui31. Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd. Baiyunshan Pharmaceutical General Factory, Guangdong, Guangzhou 510515, China;2. Guangzhou PI PI Biotech Inc., Guangdong, Guangzhou 510530, China; 3 Guangzhou Baiyunshan Mingxing Pharmaceutical Co., Ltd., Guangdong, Guangzhou 510250, China[Abstract] Objective To study the potential polymer impurities in tenofovir disoproxil fumarate tablets. Methods The samples rich in impurities (including the samples after the destructive experiment) were studied by liquid chromatography-mass spectrometry (LC-MS) with atmospheric pressure chemical ionization source (APCI ion source) and electrospray ionization source (ESI ion source), with their potential polymers found and their structures speculated. Results Dimer and trimer impurities were detected in the sample after the destructive experiment of tenofovir disoproxil fumarate tablets. Conclusion There are potential detectable polymer impurities in tenofovir disoproxil fumarate tablets: dimer and trimer impurities, among which the three impurities in the dimer are known impurities, namely H, W, and S.[Key words] Tenofovir disoproxil fumarate; Dimer; Trimer; Liquid chromatography-mass spectrometry富马酸替诺福韦二吡呋酯为美国Gilead Sciences Inc.公司1988年开发，2001年在美国首次上市，适应证为艾滋病病毒（human immunodificiency virus，HIV）感染，2008年增加乙型肝炎病毒（hepatitis B virus，HBV）感染适应证。
(优质)富马酸丙酚替诺福韦片(韦立得)(TAF)-详细说明书及重点
富马酸丙酚替诺福韦片(韦立得)(TAF)【主要成份】丙-2-基N-[(S)-({[(2R)-1-(6-氨基-9H-嘌呤-9-基)丙-2-基]-氧化}甲基)(苯氧基)磷酰基]-l-丙氨酸酯，(2E)-丁-2-烯二酸(2:1)【成份】化学名：丙-2-基N-[(S)-({[(2R)-1-(6-氨基-9H-嘌呤-9-基)丙-2-基]-氧化}甲基)(苯氧基)磷酰基]-l-丙氨酸酯，(2E)-丁-2-烯二酸(2:1)分子量：C21H29O5N6P·1/2(C4H4O4)【性状】本品为黄色、圆形的薄膜衣片。
除去包衣后，呈白色或类白色。
片剂直径8 mm，一面凹刻有“GSI”，另一面凹刻有“25”。
【适应症/功能主治】富马酸丙酚替诺福韦片适于治疗成人和青少年（年龄12 岁及以上，体重至少为35 kg）慢性乙型肝炎（参见【药理毒理】）。
【规格型号】25mg*30片【用法用量】应当由具备慢性乙型肝炎管理经验的医生开始治疗。
成人和青少年（年龄为12 岁及以上且体重至少为35 kg）：每日一次，一次一片。
口服。
需随食物服用。
漏服剂量如果漏服一剂富马酸丙酚替诺福韦片且已超过通常服药时间不足18 小时，则患者应尽快服用一剂，并恢复正常给药时间。
如果已超过通常服药时间18 小时以上，则患者不应服用漏服药物，仅应恢复正常给药时间。
如果患者在服用富马酸丙酚替诺福韦片后1 小时内呕吐，则该患者应再服用一片。
如果患者在服用富马酸丙酚替诺福韦片后超过1 小时呕吐，则该患者无需再服用一片。
特殊人群老年人无需针对年龄为65 岁及以上的患者进行富马酸丙酚替诺福韦片剂量调整（参见【药理毒理】）。
肾功能损害对于肌酐清除率(CrCl) 估计值≥15 mL/min 的成人或青少年（年龄至少为12岁，并且体重至少为35 kg）或CrCl < 15 mL/min且正在接受血液透析的患者，无需调整富马酸丙酚替诺福韦片剂量。
在进行血液透析当天，应在血液透析治疗完成后给予富马酸替诺福韦片（参见【药理毒理】）。
富马酸替诺福韦二吡呋酯杂质的合成
富马酸替诺福韦二吡呋酯杂质的合成黄小光;朱少璇;陈金瑞【摘要】为控制富马酸替诺福韦二吡呋酯的产品质量,以腺嘌呤为起始物料,合成了5种杂质:(R)-1-(6-氨基-9H-嘌呤-9-基)丙基-2-醇,(R)-[{[1-(6-氨基-9H-嘌呤-9-基)丙基-2-基]氧基}甲基]磷酸,[[{[(R)-1-(6-氨基-9H-嘌呤-9-基)丙基-2-基]氧}甲基](羟基)磷酸]氧]甲基异丙基碳酸酯,[[[{[(R)-1-(6-氨基-9H-嘌呤-9-基)丙基-2-基]氧}甲基](异并氧基)磷]氧]甲基异并氧基碳酸酯和(R)-异丙基[9-[2-[[双{[(异丙氧羰基)氧]甲氧}磷]甲氧基]丙]-9H-嘌呤-6-基]氨基碳酸酯,其结构经UV-Vis,1H NMR,13C NMR,MS(ESI)和元素分析确证.【期刊名称】《合成化学》【年(卷),期】2018(026)012【总页数】5页(P934-938)【关键词】富马酸替诺福韦二吡呋酯;腺嘌呤;杂质;合成;质量控制【作者】黄小光;朱少璇;陈金瑞【作者单位】广州白云山医药集团股份有限公司白云山制药总厂,广东广州510515;广州白云山医药集团股份有限公司白云山制药总厂,广东广州 510515;广州白云山医药集团股份有限公司白云山制药总厂,广东广州 510515【正文语种】中文【中图分类】R914.5;O626富马酸替诺福韦二吡呋酯(Chart 1)为Gilead Sciences公司研制的核苷酸逆转录酶抑制剂(NtRTIs) ，于2001年经美国FDA批准上市，主要用于治疗艾滋病(HIV 感染)。
2008年，FDA批准其用于慢性乙型肝炎(HBV感染)。
富马酸替诺福韦二吡呋酯具有耐受性好、耐药率低、停药反弹率低、肾毒性小等优点，尤其对HIV合并HBV感染患者具有较好的临床应用前景[1-4]。
替诺福韦很难被胃肠道吸收，需经酯化和成盐反应形成水溶性的富马酸替诺福韦二吡呋酯，才能发挥抗病毒作用[5-7]。
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深圳菲斯是专业进口标准品代理商，主要品牌有 TRC、TLC、Molcan、EP、BP、 USP、Sinco 等品牌标准品。 1.替卡格雷杂质 2.利伐沙班杂质 3.阿考替胺杂质 4.普拉克索杂质 5.阿哌沙班杂 质 6.氨氯地平杂质 7.硼替佐米杂质 8.比索洛尔杂质 9.阿比特龙杂质 10.非布司 他杂质 11.安立生坦杂质 12.依折麦布杂质 13.厄洛替尼杂质 14.索拉非尼杂质 15. 维格列汀杂质 16.阿伐那非杂质 17.托法替尼杂质 18.米格列奈杂质 19.沃替西汀 杂质 20 尼贝地平杂质 21.艾帕列净杂质 22.阿普斯特杂质 23.门冬氨酸缩合物 24. 依托考昔杂质 25.达格列净杂质 26.尼达尼布杂质 27.托匹司他杂质 28.坎格列净 杂质 29.帕泊昔利布杂质 30.依鲁替尼杂质 31.盐酸氨溴索杂质 32.达比加群酯杂 质等库存 库存新产品，当天发货！
富马酸替诺福韦杂质列表 名称 结构式
S-异构体
（E）-9-(1-丙烯 基)- 6-氨基-9H-嘌 呤（USP 杂质 B）
替诺福韦单吡呋 酯
n-POC-POC PMPA
二聚体
混合二聚体
EOC-POC PMPA
DEC-POC PMPA
Des-Methyl TDF （去甲基替诺福 韦二吡呋酯）
MOC-POC PMPA