制药用水美国USP附录翻译稿件

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美国药典凡例中英文 USP32 NF27 General Notice

求取代凡例或附录的要求。
4. MONOGRAPHS AND GENERAL CHAPTERS 正文和附录
4.10 Monographs 专论 Monographs set forth the article's name, definition, specification, and other requirements related to packaging, storage, and labeling. The specification consists of tests, procedures, and acceptance criteria that help ensure the identity, strength, quality, and purity of the article. For general requirements relating to specific monograph sections, see section 5, Monograph Components. 专论阐述了药品的名称，定义，质量标准，及其他和包装，储存和标签相关的要求。质量标准包括测试，过程，及可接受范围，保证了药品的特性，规格，质量和纯度。对于特定专论相关的一般要求，参见章节 5“专论构成”。 Because monographs may not provide standards for all relevant characteristics, some official substances may conform to the USP or NF standard but differ with regard to nonstandardized properties that are relevant to their use in specific preparations. To assure interchangeability in such instances, users may wish to ascertain functional equivalence or determine such characteristics before use. 由于专论可能无法提供全部特性的标准，有些药物可能符合 USP 或 NF 标准，但是其在特定的制备中使用的相关非标准性质可能有所不同。为确保这个情况的互通性，使用者在使用前须确定其功能对等或确定其特征。 4.10.10 Applicability of Test Procedures 测试过程的适用性 A single monograph may include several different tests, procedures, and/or acceptance criteria that reflect attributes of different manufacturers' articles. Such alternatives may be presented for different polymorphic forms, impurities, hydrates, and dissolution cases. Monographs indicate the

美国药典（USP34）附录-171英文

171 VITAMIN B12 ACTIVITY ASSAYUSP Reference Standards 11— USP Cyanocobalamin RS.Assay Preparation— Place a suitable quantity of the material to be assayed, previously reduced to a fine powder if necessary and accurately measured or weighed, in an appropriate vessel containing, for each g or mL of material taken, 25 mL of an aqueous extracting solution prepared just prior to use to contain, in each 100 mL, 1.29 g of disodium phosphate, 1.1 g of anhydrouscitric acid, and 1.0 g of sodium metabisulfite. Autoclave the mixture at 121 for 10 minutes. Allow any undissolved particles of the extract to settle, and filter or centrifuge, if necessary. Dilute an aliquot of the clear solution with water so that the final test solution contains vitamin B12 activity approximately equivalent to that of the Standard Cyanocobalamin Solution which is added to the assay tubes.Standard Cyanocobalamin Stock Solution— To a suitable quantity of USP Cyanocobalamin RS, accurately weighed, add sufficient 25 percent alcohol to make a solution having a known concentration of 1.0 µg of cyanocobalamin per mL. Store in a refrigerator.Standard Cyanocobalamin Solution— Dilute a suitable volume of Standard Cyanocobalamin Stock Solution with water to a measured volume such that after the incubation period as described for Procedure, the difference in transmittance between the inoculated blank and the 5.0-mL level of the Standard Cyanocobalamin Solution is not less than that which corresponds to a difference of 1.25 mg in dried cell weight. This concentration usually falls between 0.01 ng and 0.04 ng per mL of Standard Cyanocobalamin Solution. Prepare a fresh standard solution for each assay.Basal Medium Stock Solution— Prepare the medium according to the following formula and directions. A dehydrated mixture containing the same ingredients may be used provided that, when constituted as directed in the labeling, it yields a medium comparable to that obtained from the formula given herein.Add the ingredients in the order listed, carefully dissolving the cystine and tryptophane in the hydrochloric acid before adding the next eight solutions in the resulting solution. Add 100 mL of water, mix, and dissolve the dextrose, sodium acetate, and ascorbic acid. Filter, if necessary, add the polysorbate 80 solution, adjust the solution to a pH between 5.5 and 6.0 with 1 N sodium hydroxide, and add purified water to make 250 mL.L-Cystine0.1 gL-Tryptophane0.05 g1 N Hydrochloric Acid10 mLAdenine-Guanine-Uracil Solution5 mLXanthine Solution 5 mLVitamin Solution I10 mLVitamin Solution II10 mLSalt Solution A 5 mLSalt Solution B 5 mLAsparagine Solution 5 mLAcid-hydrolyzed Casein Solution25 mLDextrose, Anhydrous10 gSodium Acetate, Anhydrous 5 gAscorbic Acid 1 gPolysorbate 80 Solution 5 mLAcid-Hydrolyzed Casein Solution— Prepare as directed under CalciumPantothenate Assay 91.Asparagine Solution— Dissolve 2.0 g of L-asparagine in water to make 200 mL. Store under toluene in a refrigerator.Adenine–Guanine–Uracil Solution— Prepare as directed under CalciumPantothenate Assay 91.Xanthine Solution— Suspend 0.20 g of xanthine in 30 mL to 40 mL of water, heat to about 70, add 6.0 mL of 6 N ammonium hydroxide, and stir until the solid is dissolved. Cool, and add water to make 200 mL. Store under toluene in a refrigerator.Salt Solution A— Dissolve 10 g of monobasic potassium phosphate and 10 g of dibasic potassium phosphate in water to make 200 mL. Add 2 drops of hydrochloric acid, and store under toluene.Salt Solution B— Dissolve 4.0 g of magnesium sulfate, 0.20 g of sodium chloride, 0.20 g of ferrous sulfate, and 0.20 g of manganese sulfate in water to make 200 mL. Add 2 drops of hydrochloric acid, and store under toluene. Polysorbate 80 Solution— Dissolve 20 g of polysorbate 80 in alcohol to make 200 mL. Store in a refrigerator.Vitamin Solution I— Dissolve 10 mg of riboflavin, 10 mg of thiamine hydrochloride, 100 µg of biotin, and 20 mg of niacin in 0.02 N glacial acetic acid to make 400 mL. Store, protected from light, under toluene in a refrigerator.Vitamin Solution II— Dissolve 20 mg of para-aminobenzoic acid, 10 mg of calcium pantothenate, 40 mg of pyridoxine hydrochloride, 40 mg of pyridoxal hydrochloride, 8 mg of pyridoxamine dihydrochloride, and 2 mg of folic acid in dilute neutralized alcohol (1 in 4) to make 400 mL. Store, protected from light, in a refrigerator.Tomato Juice Preparation— Centrifuge commercially canned tomato juice so that most of the pulp is removed. Suspend about 5 g per L of analytical filter-aid in the supernatant, and filter, with the aid of reduced pressure, through a layer of the filter-aid. Repeat, if necessary, until a clear, straw-colored filtrate is obtained. Store under toluene in a refrigerator.Culture Medium— [NOTE—A dehydrated mixture containing the same ingredients may be used provided that, when constituted as directed in the labeling, it yields a medium equivalent to that obtained from the formula given herein. ]Dissolve 0.75 g of water-soluble yeast extract, 0.75 g of dried peptone, 1.0 g of anhydrous dextrose, and 0.20 g of potassium biphosphate in 60 mL to 70 mL of water. Add 10 mL of Tomato Juice Preparation and 1 mL of Polysorbate 80 Solution. Adjust the solution with 1 N sodium hydroxide to a pH of 6.8, and add water to make 100 mL. Place 10-mL portions of the solution in test tubes, and plug with cotton. Sterilize the tubes and contents in an autoclave at 121 for 15 minutes. Cool as rapidly as possible to avoid color formation resulting from overheating the medium.Suspension Medium— Dilute a measured volume of Basal Medium Stock Solution with an equal volume of water. Place 10-mL portions of the diluted medium in test tubes. Sterilize, and cool as directed above for the Culture Medium.Stock Culture of Lactobacillus leichmannii— To 100 mL of Culture Medium add 1.0 g to 1.5 g of agar, and heat the mixture, with stirring, on a steam bath, until the agar dissolves. Place approximately 10-mL portions of the hotsolution in test tubes, cover the tubes suitably, sterilize at 121 for 15 minutes in an autoclave (exhaust line temperature), and allow the tubes to cool in an upright position. Inoculate three or more of the tubes, by stab transfer of a pure culture of Lactobacillus leichmannii.* (Before first using a fresh culture in this assay, make not fewer than 10 successive transfers of the culture in a 2-week period.) Incubate 16 to 24 hours at any selected temperature between30 and 40 but held constant to within ±0.5, and finally store in a refrigerator.Prepare fresh stab cultures at least three times each week, and do not use them for preparing the inoculum if more than 4 days old. The activity of the microorganism can be increased by daily or twice-daily transfer of the stab culture, to the point where definite turbidity in the liquid inoculum can be observed 2 to 4 hours after inoculation. A slow-growing culture seldom gives a suitable response curve, and may lead to erratic results.Inoculum— [NOTE—A frozen suspension of Lactobacillus leichmannii may be used as the stock culture, provided it yields an inoculum comparable to a fresh culture. ]Make a transfer of cells from the Stock Culture of Lactobacillus leichmannii to 2 sterile tubes containing 10 mL of the Culture Medium each. Incubate these cultures for 16 to 24 hours at any selected temperature between 30 and 40 but held constant to within ±0.5. Under aseptic conditions, centrifuge the cultures, and decant the supernatant. Suspend the cells from the culture in 5 mL of sterile Suspension Medium, and combine. Using sterile Suspension Medium, adjust the volume so that a 1 in 20 dilution in saline TS produces 70% transmittance when read on a suitable spectrophotometer that has been set at a wavelength of 530 nm, equipped with a 10-mm cell, and read against saline TS set at 100% transmittance. Prepare a 1 in 400 dilution of the adjusted suspension using Basal Medium Stock Solution, and use it for the test inoculum. (This dilution may be altered, when necessary, to obtain the desired test response.)Calibration of Spectrophotometer— Check the wavelength of the spectrophotometer periodically, using a standard wavelength cell or other suitable device. Before reading any tests, calibrate the spectrophotometer for 0% and 100% transmittance, using water and with the wavelength set at 530 nm.Procedure— Cleanse meticulously by suitable means, followed preferably byheating at 250 for 2 hours, hard-glass test tubes, about 20 mm × 150 mm in size, and other necessary glassware because of the high sensitivity of the test organism to minute amounts of vitamin B 12 activity and to traces of many cleansing agents.To test tubes add, in duplicate, 1.0 mL, 1.5 mL, 2.0 mL, 3.0 mL, 4.0 mL, and 5.0 mL, respectively, of the Standard Cyanocobalamin Solution. To each of these tubes and to four similar empty tubes add 5.0 mL of Basal Medium Stock Solution and water to make 10 mL.To similar test tubes add, in duplicate, respectively, 1.0 mL, 1.5 mL, 2.0 mL, 3.0 mL, and 4.0 mL of the Assay Preparation. To each tube add 5.0 mL of Basal Medium Stock Solution and water to make 10 mL. Place one complete set of standard and assay tubes together in one tube rack and the duplicate set in a second rack or section of a rack, preferably in random order.Cover the tubes suitably to prevent bacterial contamination, and sterilize thetubes and contents in an autoclave at 121 for 5 minutes, arranging to reach this temperature in not more than 10 minutes by preheating the autoclave, if necessary. Cool as rapidly as practicable to avoid color formation resulting from overheating the medium. Take precautions to maintain uniformity of sterilizing and cooling conditions throughout the assay, since packing tubes too closely in the autoclave, or overloading it, may cause variation in the heating rate.Aseptically add 0.5 mL of Inoculum to each tube so prepared, except two of the four containing no Standard Cyanocobalamin Solution (the uninoculatedblanks). Incubate the tubes at a temperature between 30 and 40 held constant to within ±0.5, for 16 to 24 hours.Terminate growth by heating to a temperature not lower than 80 for 5 minutes. Cool to room temperature. After agitating its contents, place the container in a spectrophotometer that has been set at a wavelength of 530 nm, and read the transmittance when a steady state is reached. This steady state is observed a few seconds after agitation when the reading remains constant for 30 seconds or more. Allow approximately the same time interval for the reading on each tube.With the transmittance set at 100% for the uninoculated blank, read the transmittance of the inoculated blank. If the difference is greater than 5% or if there is evidence of contamination with a foreign microorganism, disregard the results of the assay.With the transmittance set at 100% for the uninoculated blank, read the transmittance of each of the remaining tubes. Disregard the results of the assay if the slope of the standard curve indicates a problem with sensitivity.Calculation— Prepare a standard concentration-response curve by the following procedure. Test for and replace any aberrant individual transmittances. For each level of the standard, calculate the response from the sum of the duplicate values of the transmittances (∑) as the difference, y = 2.00 – ∑. Plot this response on the ordinate of cross-section paper against the logarithm of the mL of Standard Cyanocobalamin Solution per tube on the abscissa, using for the ordinate either an arithmetic or a logarithmic scale, whichever gives the better approximation to a straight line. Draw the straight line or smooth curve that best fits the plotted points.Calculate the response, y, adding together the two transmittances for each level of the Assay Preparation. Read from the standard curve the logarithm of the volume of the Standard Preparation corresponding to each of those values of y that falls within the range of the lowest and highest points plotted for the standard. Subtract from each logarithm so obtained the logarithm ofthe volume, in mL, of the Assay Preparation to obtain the difference, x , for each dosage level. Average the values of x for each of three or more dosage levels to obtain x = M ', the log-relative potency of the Assay Preparation. Determine the quantity, in µg, of USP Cyanocobalamin RS corresponding to the cyanocobalamin in the portion of material taken for assay by the equation antilog M = antilog (M ' + log R ), in which R is the number of µg ofcyanocobalamin that was assumed to be present in each mg (or capsule or tablet) of the material taken for assay.Replication— Repeat the entire determination at least once, using separately prepared Assay Preparations. If the difference between the two log potencies M is not greater than 0.08, their mean, M , is the assayed log-potency of the test material (see Vitamin B 12 Activity Assay under Design and Analysis ofBiological Assays 111). If the two determinations differ by more than 0.08, conduct one or more additional determinations. From the mean of two or more values of M that do not differ by more than 0.15, compute the mean potency of the preparation under assay.* Pure cultures of Lactobacillus leichmannii may be obtained as No. 7830 from the American Type Culture Collection, 10801 University Blvd., Manassas, VA 20110.General Chapter Curtis Phinney1-301-816-8540(DSN05) Dietary Supplements - Non-BotanicalsReferenceStandards Lili Wang, TechnicalServices Scientist 1-301-816-8129。

USP39-1231制药用水-中文

<1231>制药用水引言水是药物制剂、药物活性成分和中间体的工艺、配方和制造中最常用的原料、组分和溶剂，水也是药典品种和分析试剂。

本指导性通则提供水的品种正文中不包含的补充质量要求、用于改进水质量的工艺技术，以及选择水源时应考虑的水的最低质量标准。

本指导性通则不能代替美国和国际上（ICH 或WHO）GMP 文件中已有的关于水的法规和指导原则、工艺指南或其他部门（FDA、EPA 或WHO）关于水的指导原则。

本通则内容为帮助使用者深入了解制药用水的重要性，以及与水特有关系的微生物污染和化学污染问题。

本通则不能包括制药用水全部内容，仅包括水的制备工艺、贮备和使用中应考虑的基本问题。

用户有责任按照药典品种所用水的类型，保证制药用水及其制造符合有关政府法规、指南，以及药典规定。

制药用水化学纯度控制十分重要，是本药典有关正文的主要内容。

与其他药典品种不同的是，制药过程用的批量水（bulk water）的正文（纯化水和注射用水）规定水的制法，因为制水工艺设备的性质和耐用性直接与出水的纯度有关。

水的正文中列出的化学纯度检验标准应被视为最低要求。

特殊用途的水有更严格的质量要求。

制药用水应用的基本指南见品种正文，本通则做进一步说明。

在许多水的用途中，微生物质量控制是很重要的。

大多数包装的水，其品种正文要求无菌，系其用途与健康和安全有关。

USP 批量水的品种正文中不收载微生物标准。

制药用水有不同用途，有的要求很高的微生物控制，有的则不需要。

特定的批量水所需的微生物标准取决于其用途。

对于有些用户，这些检测项目没有必要。

但水的有些用途要求非常高的微生物控制，以防止水在纯化、贮藏和运输中微生物的生长。

对于即用或连续供应的制药用水，微生物标准也不合用。

微生物标准的评估要用检测方法，耗时48~72小时方能得到结果。

制药用水一般连续生产，制好后即在产品和生产过程中使用，检测结果出来前，水已经用过了。

水的质量不符合药典规定，则要对情况进行调查，并对前次合格结果和后次检验合格结果之间的全部批号的产品，做出放行还是不放行的决定。

(完整版)美国药典USP31(921)翻译版(上)

921WATER DETERMINATION水分测定Many Pharmacopeial articles either are hydrates or contain water in adsorbed form. As a result, the determination of the water content is important in demonstrating compliance with the Pharmacopeial standards. Generally one of the methods given below is called for in the individual monograph, depending upon the nature of the article. In rare cases, a choice is allowed between two methods. When the article contains water of hydration, the Method I (Titrimetric), the Method II (Azeotropic), or the Method III (Gravimetric) is employed, as directed in the individual monograph, and the requirement is given under the heading Water.很多药典物品要么是水合物，要么含有处于吸附状态的水。

因此，测定水分含量对于证实与药典标准的符合性是很重要的。

通常，在具体的各论中会根据该物品的性质，要求使用下面若干方法中的一个。

偶尔，会允许在2个方法中任选一个。

当该物品含有水合状态的水，按照具体各论中的规定，使用方法I（滴定测量法）、方法II（恒沸测量法）、或方法III（重量分析法），这个要求在标题水分项下给出。

USP-1231制药工艺用水

USP <1231>制药工艺用水在药物制品的生产、流程和合成中，水是最常用的一种物质，原料或者成分。

在水净化、贮存、输送期间，无处不在的微生物有可能在水中扩散，因此对制品上述过程中的水中的微生物质量控制是极其重要的。

如果未经控制即直接用于最终产品上，那些微生物或者它们的代谢产物最终对药品产生不利的后果。

用在药品早期阶段和作为各种净化水的原料或供水者必须达到环境保护组织（EPA）公布的国家饮用水标准（NP DWR）（40 CFR 141）。

欧盟或日本类似的饮用水规定也是可以接受的。

这些规定保证水中不含有大肠杆菌。

如果确定水中含有这种污染源，这也许预示或者表明还存在其它微生物污染源，其中包括使人致病的一些病菌。

另外，达到国家饮用水标准并不排除没有考虑到水中含有现在认为还不是关系公众健康的其它的微生物，这些微生物是药品成分和产品合成的一个危害因素，或影响其药品效果。

基于这个原因，现在把制药工艺用水分为不同的级别。

水的归类饮用水——虽然饮用水没有通过专题来论述，但它必须遵循EPA NPPWR（见上）或者欧盟和日本有类似的标准。

饮用水可以从不同的水源获得，其中包括公共事业用水或私人使用水（例如：水井）或者多种方式相结合。

饮用水可以用在化工合成的初期阶段和制药设备初期阶段的清洗。

它是作为生产制药用水指定的供水源。

饮用水的质量的差异受季节变化的影响，因此，生产制药用水的操作步骤应考虑到这一点而进行设计。

净化水——净化水（参见美国药典专著）在成药的正式生产中作为赋形剂，同样用于制药方面和清洗一定的机器设备和化学药用原料的成药。

净化水必须达到离子有机化学药品纯度的要求，同时还要避免微生物扩散。

通常使用饮用水作为供给水，通过一系列操作使水纯化。

这些操作包括去离子、蒸馏、离子交换、反向渗透、过滤或者其它适宜的程序。

净化水系统必须通过证实。

净化水系统是在环绕的环境中对水进行生产、贮存和循环，因而极易受粘性微生物膜的感染。

制药用水的种类范文

制药用水的种类范文制药用水是指用于制药工业生产过程中的一种特殊水源，其质量标准和要求与普通生活用水存在很大不同。

制药用水在药品的研发、生产、检验以及清洗设备等各个环节都起到至关重要的作用，因此对于制药企业来说，选择合适的制药用水种类至关重要。

根据国际制药协会（International Pharmaceutical Federation, FIP）和美国药典（United States Pharmacopeia, USP）的相关规定，制药用水主要分为以下几种类别：1. 注射用水（Water for Injection, WFI）注射用水是一种高纯度的水，用于制备注射液、溶液或氨基酸等需要直接进入人体的药物。

注射用水的要求非常严格，包括无菌、无有害微生物、低溶解氧、无有机物和重金属等。

2. 纯净水（Purified Water）纯净水是一种经过特殊处理的水源，用于制备口服药物、液体药剂、洗涤剂、溶剂等。

纯净水要求无菌、无有害微生物，同时要求低溶解氧、无有机物和重金属等。

3. 蒸馏水（Distilled Water）蒸馏水是一种经过蒸馏过程处理的水源，用于制备药物的配方、制备溶剂等。

蒸馏水要求无菌、无有害微生物，同时要求低溶解氧、无有机物和重金属等。

4. 试剂级水（Reagent Grade Water）试剂级水是一种用于实验室的纯化水源，用于制备试剂、标准品和实验操作等。

试剂级水要求低溶解氧、无有机物和重金属等。

5. 洗涤水（Washing Water）洗涤水主要用于制药设备的清洗和消毒，要求无菌、无有害微生物，同时要求低溶解氧、无有机物和重金属等。

为了满足制药用水的各项要求，制药企业通常会采用一系列的水处理设备和工艺，包括反渗透、电离子交换、超滤、紫外线消毒等。

此外，为了确保制药用水的质量稳定和符合标准，制药企业还需要实施严格的水质监控和质量管理措施。

综上所述，制药用水是制药工业生产中不可或缺的一种特殊水源，根据其不同用途，可以分为注射用水、纯净水、蒸馏水、试剂级水和洗涤水等。

(完整版)美国药典USP31(921)翻译版(上)

因此，测定水分含量对于证实与药典标准的符合性是很重要的。

通常，在具体的各论中会根据该物品的性质，要求使用下面若干方法中的一个。

偶尔，会允许在2个方法中任选一个。

制药用水微生物指导USP32中英文

微生物考虑事项主要的外源性微生物污染是进水源。

进水的质量必须至少符合饮用水的质量标准，大肠杆菌量是需要控制的。

饮用水还可存在其他微生物，主要是革兰氏阴性细菌【G(-)菌】。

这些微生物可以损害随后的纯化步骤。

其他潜在的外源性微生物污染有：未保护好的排气口，不完善的空气过滤器，从污染的出口处倒流，排水气闸以及活性炭和去离子树脂更换。

对水系统的设计和维修保养应给予足够的注意以最大限度地减少外来微生物污染。

单元操作可能是内源性微生物污染的主要根源。

进水的微生物可吸着在炭床，去离子树脂，过滤膜以及其他设备的运行表面，诱发生成生物膜。

有些微生物为在低营养环境下生存，以生物膜作为适应性反应。

生物膜的微生物可不受许多杀菌剂的作用。

当微生物脱落下来并进入水系统的其他区域，在下游可产生菌落。

微生物可依附在悬浮微粒上，如炭床细粉，也是随后的纯化设备和分配系统的污染源。

分配系统是内源性微生物污染另一根源。

微生物可在管道壁，阀门以及其他区域形成菌落，并增殖形成生物膜，生物膜就成为不断的微生物污染源。

内毒素考虑事项内毒素是细胞膜的脂质多糖体，是G(-)菌的细胞外壁。

G(-)菌很快形成生物膜成为内毒素源。

内毒素可以和活的微生物联合，也可以是死的微生物裂片，或者是游离的分子。

游离的内毒素可以从细胞表面或水系统生成的生物膜中释放出来，或者是从进水进入水系统。

内毒素量可以通过控制水系统的微生物的引入及增殖以最大限量地加以减少。

这可以用各种不同的单元操作在处理系统中加以除去，也可通过系统消毒加以除去。

其他控制方法包括在管路上或在使用点上装超滤或带电荷的过滤器。

内毒素可以按细菌内毒素试验所述方法加以监测。

方法学考虑事项水系统微生物监测的目的是要提供足够的有关生产水的微生物质量控制的资料。

产品的质量要求决定水的质量。

用数据趋向分析方法以及限定特殊的禁忌微生物可使微生物质量控制保持在一定的水平。

当然，不一定要对所有存在的微生物加以检测。

监测计划和方法学应能指出不良的趋势，而且能检测出对最终成品或消费者可能有害的微生物。

美国药典对工艺用水的要求

Water for InjectionNOTE—For microbiological guidance, see general information chapter Water for Pharmaceutical Purposes 1231.» Water for Injection is water purified by distillation or a purification process that is equivalent or superior to distillation in the removal of chemicals and microorganisms. It is prepared from water complying with the U.S. Environmental Protection Agency National Primary Drinking Water Regulations or with the drinking water regulations of the European Union, Japan, or with the World Health Organization's Guidelines for Drinking Water Quality. It contains no added substance.NOTE—Water for Injection is intended for use in the preparation of parenteral solutions. Where used for the preparation of parenteral solutions subject to final sterilization, use suitable means to minimize microbial growth, or first render the Water for Injection sterile and, thereafter, protect it from microbial contamination. For parenteral solutions that are prepared under aseptic conditions and are not sterilized by appropriate filtration or in the final container, first render the Water for Injection sterile and, thereafter, protect it from microbial contamination. The tests for Total organic carbon and Water conductivity apply to Water for Injection produced on site for use in manufacturing. Water for Injection packaged in bulk for commercial use elsewhere meets the requirement of the test for Bacterial endotoxins as indicated below and the requirements of all the tests under Sterile Purified Water, except Labeling.USP R EFERENCE STANDARDS 11—USP 1,4-Benzoquinone RS.USP Endotoxin RS . USP Sucrose RS . B ACTERIAL ENDOTOXINS 85— It contains less than 0.25 USP Endotoxin Unit per mL.T OTAL ORGANIC CARBON 643: meets the requirements.W ATER CONDUCTIVITY 645: meets the requirements.contacting USP.Topic/Question ContactExpert Committee Monograph Antonio Hernandez-Cardoso, M.Sc.Scientist, Latin AmericanSpecialist1-301-816-8308(PW05) PharmaceuticalWaters 05Reference Standards Lili Wang, TechnicalServices Scientist1-301-816-8129**************85 Radhakrishna STirumalai, Ph.D.Senior Scientist1-301-816-8339 (MSA05) Microbiology and Sterility AssuranceUSP32–NF27 Page 3870Pharmacopeial Forum : Volume No. 35(2) Page 316《药品生产质量管理规范（2010年修订）》第九十六条制药用水应当适合其用途，并符合《中华人民共和国药典》的质量标准及相关要求。

[VIP专享]USP33-1231制药用水__中文译稿

USP33-制药用水<1231> 制药用水<1231>引言在药品、原料药和中间体，药典产品以及分析试剂的加工、制备和生产过程中，水被广泛用作一原料，组分和溶剂。

此通用章节的信息提供了有关水的其它信息：未被包括在的水的专论中的属性，可以用以提高水质量的处理技术，以及在选择水源时应考虑最低水质量标准的描述。

此信息章节并未打算替代现有的条例或指导，现有的这些条例或指导涉及USA和国际的（ICH或WHO）的GMP问题，工程指导或其它关于水的条例（FDA、EPA或WHO）指导。

其内容有有助于使用者更好地理解制药用水问题以及一些仅针对水的微生物和化学问题。

此章节并不是关于制药用水的一个全面综合性的文件。

它包括在水的处理、贮存和使用时需要考虑的基本信息点。

保证制药用水以及生产符合相适用的政府条例、指南和各种类型的水的药典标准是使用者的职责。

这些水的化学纯度的控制是很重要的，并且是本药典中各论的主要目的。

与其它药典产品不同，大批量水专论（纯化水和注射用水）也限制此产品是如何被生产的，因为认为纯化过程的本质与完善程度与（水）最终的纯度直接相关。

在这些个论中所列的化学属性应被看作为一组最低的规范要求。

对于某些应用来说，可能需要更加严格的规范以保证适合其特定的用途。

关于这些水的适当应用的基本指导可以在正文中找到，并且在本章节中给出更进一步的解释。

对于很多水的用途来说，控制其微生物质量是很重要的。

由于健康与安全的原因，所有具有药典标准的包装形式的水要求是无菌的，因为这些水的一些预期用途有此要求。

USP认为大批量专论水的微生物规范是不适当的，并且未被包括在这些水的专论中。

这些水可以被用于不同的用途，一些要求严格的微生物控制，而一些却未要求。

对于一给定大批量水来说，所需的微生物规范取决于其用途。

对于一些没有相关规范和检测的使用者来说，将不必需负担此难于控制的（水的微生物）属性的单个规范。

然而，一些应用可能需要甚至更加严格的微生物控制，以避免微生物的繁殖，而微生物在水的纯化、贮存和分配过程中无处不在。

美国药典usp1231制药用水中文翻译.doc

美国药典usp1231制药用水中文翻译.docUSP33-制药用水<1231>制药用水<1231>引言在药品、原料药和中间体，药典产品以及分析试剂的加工、制备和生产过程中，水被广泛用作一原料，组分和溶剂。

其内容有有助于使用者更好地理解制药用水问题以及一些仅针对水的微生物和化学问题。

此章节并不是关于制药用水的一个全面综合性的文件。

它包括在水的处理、贮存和使用时需要考虑的基本信息点。

保证制药用水以及生产符合相适用的政府条例、指南和各种类型的水的药典标准是使用者的职责。

这些水的化学纯度的控制是很重要的，并且是本药典中各论的主要目的。

在这些个论中所列的化学属性应被看作为一组最低的规范要求。

对于某些应用来说，可能需要更加严格的规范以保证适合其特定的用途。

关于这些水的适当应用的基本指导可以在正文中找到，并且在本章节中给出更进一步的解释。

对于很多水的用途来说，控制其微生物质量是很重要的。

由于健康与安全的原因，所有具有药典标准的包装形式的水要求是无菌的，因为这些水的一些预期用途有此要求。

USP认为大批量专论水的微生物规范是不适当的，并且未被包括在这些水的专论中。

这些水可以被用于不同的用途，一些要求严格的微生物控制，而一些却未要求。

对于一给定大批量水来说，所需的微生物规范取决于其用途。

对于一些没有相关规范和检测的使用者来说，将不必需负担此难于控制的（水的微生物）属性的单个规范。

USP30_1231-WATER FOR PHARMACEUTICAL PURPOSES翻译(节选)

USP30-- <1231> WATER FOR PHARMACEUTICAL PURPOSESUSP30 <1231> 制药用水（节选饮用水部分）SOURCE OR FEED WATER CONSIDERATIONS水源或供水系统To ensure adherence to certain minimal chemical and microbiological quality standards, water used in the production of drug substances or as source or feed water for the preparation of the various types of purified waters must meet the requirements of the National Primary Drinking Water Regulations (NPDWR) (40 CFR 141) issued by the U.S. Environmental Protection Agency (EPA) or the drinking water regulations of the European Union or Japan, or the WHO drinking water guidelines.为了保证能达到某些化学和微生物的最低质量标准，用于药品生产的水或者是用于制备各种纯化水的水源必须要符合美国环境保护局（EPA）发布的国家基本饮用水规定（NPDWR ）(40 CFR 141)。

欧盟、日本或WHO的有关饮用水规定也可适用。

Limits on the types and quantities of certain organic and inorganic contaminants ensure that the water will contain only small, safe quantities of potentially objectionable chemical species. Therefore, water pretreatment systems will only be challenged to remove small quantities of these potentially difficult-to-remove chemicals. Also, control of objectionable chemical contaminants at the source-water stage eliminates the need to specifically test for some of them (e.g., trihalomethanes and heavy metals) after the water has been further purified.对某些有机和无机污染物的种类和数量进行限定可以保证水中只含有微小的，可靠数量的潜在的化学物质。

(完整版)美国药典USP31(921)翻译版(下)

Method Ib (Residual Titration) 方法Ib（残留滴定）Principle— See the information given in the section Principle under Method Ia. In the residual titration, excess Reagent is added to the test specimen, sufficient time is allowed for the reaction to reach completion, and the unconsumed Reagent is titrated with a standard solution of water in a solvent such as methanol. The residual titration procedure is applicable generally and avoids the difficulties that may be encountered in the direct titration of substances from which the bound water is released slowly.原理：见方法Ia项下原理部分给出的信息。

在残留滴定中，额外的试剂被加入到供试样品中，为反应的完成留下了充分的时间，并且将未消耗掉的试剂与水和某种溶剂（例如，甲醇）的标准溶液一起滴定。

残留滴定程序通常是可行的，并避免了可能在直接滴定该物质过程中遇到的困难，这些物质中被束缚水分释放得很缓慢。

Apparatus, Reagent, and Test Preparation— Use Method Ia.仪器、试剂、供试配制液：同方法Ia。

Standardization of Water Solution for Residual Titration— Prepare a Water Solution by diluting 2 mL of water with methanol or other suitable solvent to 1000 mL. Standardize this solution by titrating 25.0 mL with the Reagent, previously standardized as directed under Standardization of the Reagent. Calculate the water content, in mg per mL, of the Water Solution taken by the formula:用于残留滴定的水溶液的标准化：以甲醇或其他适当溶剂将2mL水稀释至1000mL，以配制水溶液。

美国药典(USP34)附录-115英文

115DEXPANTHENOL ASSAYThe following procedure is provided for the determination of dexpanthenol as an ingredient of multiple-vitamin preparations. It is applicable also to the determination of the dextrorotatory component of racemic panthenol and of other mixtures containing dextrorotatory panthenol.Media may be prepared as described hereinafter, or dehydrated mixtures yielding similar formulations may be used provided that, when reconstituted as directed by the manufacturer or distributor, they have growth-promoting properties equal to or superior to those obtained from the formulas given herein.USP Reference Standards 11—USP Dexpanthenol RS.Standard Stock Solution of Dexpanthenol— Dissolve an accurately weighed quantity of USP Dexpanthenol RS in water, dilute with water to obtain a solution having a known concentration of about 800 µg per mL, and mix. Store in a refrigerator, protected from light, and use within 30 days.Standard Preparation— On the day of the assay, prepare a water dilution of the Standard Stock Solution of Dexpanthenol to contain 1.2 µg of dexpanthenol per mL.Assay Preparation— Proceed as directed in the individual monograph for preparing a solution expected to contain approximately the equivalent of the dexpanthenol concentration in the Standard Preparation.Modified Pantothenate Medium—Acid-Hydrolyzed Casein Solution 25 mL Cystine–Tryptophane Solution 25 mLPolysorbate 80 Solution 0.25mL Dextrose, Anhydrous 10 g Sodium Acetate, Anhydrous 5 g Adenine–Guanine–Uracil Solution 5 mL Riboflavin–Thiamine Hydrochloride–Biotin Solution 5 mL5 mL Para-aminobenzoic Acid–Niacin–Pyridoxine HydrochlorideSolutionSalt Solution A 5 mL Salt Solution B 5 mL Pyridoxal-Calcium Pantothenate Solution 5 mL Polysorbate 40–Oleic Acid Solution 5 mL Dissolve the anhydrous dextrose and sodium acetate in the solutions previously mixed, and adjust with 1 N sodium hydroxide to a pH of 6.8. Finally, dilute with water to 250 mL, and mix.Double-Strength Modified Pantothenate Medium— Prepare as directed under Modified Pantothenate Medium, but make the final dilution to 125 mL instead of 250 mL. Prepare fresh.Acid-Hydrolyzed Casein Solution— Mix 100 g of vitamin-free casein with 500 mL of 6 N hydrochloric acid, and reflux the mixture for 8 to 12 hours. Remove the hydrochloric acid from the mixture by distillation under reduced pressure until a thick paste remains. Redissolve the resulting paste in about 500 mL of water, adjust the solution with 1 N sodium hydroxide to a pH of 3.5 ± 0.1, and add water to make 1000 mL. Add 20 g of activated charcoal, stir for 1 hour, and filter. Repeat the treatment with activated charcoal. Store under toluene in a refrigerator at a temperature not below 10. Filter the solution if a precipitate forms during storage.Cystine–Tryptophane Solution— Suspend 4.0 g of L-cystine and 1.0 g ofL-tryptophane (or 2.0 g of D,L-tryptophane) in 700 mL to 800 mL of water, heatto 75 ± 5, and add dilute hydrochloric acid (1 in 2) dropwise, with stirring, until the solids are dissolved. Cool, add water to make 1000 mL, and mix. Store under toluene in a refrigerator at a temperature not below 10.Adenine–Guanine–Uracil Solution— Dissolve 200 mg each of adenine sulfate, guanine hydrochloride, and uracil, with the aid of heat, in 10 mL of 4 N hydrochloric acid, cool, add water to make 200 mL, and mix. Store under toluene in a refrigerator.Polysorbate 80 Solution— Dissolve 25 g of polysorbate 80 in alcohol to make 250 mL, and mix.Riboflavin–Thiamine Hydrochloride–Biotin Solution— Prepare a solution containing, in each mL, 20 µg of riboflavin, 10 µg of thiamine hydrochloride, and 0.04 µg of biotin, by dissolving riboflavin, thiamine hydrochloride, and biotin in 0.02 N acetic acid. Store, protected from light, under toluene in a refrigerator.Para-aminobenzoic Acid–Niacin–Pyridoxine Hydrochloride Solution— Prepare a solution in neutral 25 percent alcohol to contain 10 µg of para-aminobenzoic acid, 50 µg of niacin, and 40 µg of pyridoxine hydrochloride in each mL. Store in a refrigerator.Salt Solution A— Dissolve 25 g of monobasic potassium phosphate and 25 g of dibasic potassium phosphate in water to make 500 mL. Add 5 drops of hydrochloric acid, mix, and store under toluene.Salt Solution B— Dissolve 10 g of magnesium sulfate, 0.5 g of sodium chloride,0.5 g of ferrous sulfate, and 0.5 g of manganese sulfate in water to make 500 mL. Add 5 drops of hydrochloric acid, mix, and store under toluene.Pyridoxal–Calcium Pantothenate Solution— Dissolve 40 mg of pyridoxal hydrochloride and 375 µg of calcium pantothenate in 10 percent alcohol to make 2000 mL, and mix. Store in a refrigerator, and use within 30 days.Polysorbate 40–Oleic Acid Solution— Dissolve 25 g of polysorbate 40 and 0.25 g of oleic acid in 20 percent alcohol to make 500 mL, and mix. Store in a refrigerator, and use within 30 days.Stock Culture of Pediococcus acidilactici— Dissolve in about 800 mL of water, with the aid of heat, 6.0 g of peptone, 4.0 g of pancreatic digest of casein, 3.0 g of yeast extract, 1.5 g of beef extract, 1.0 g of dextrose, and 15.0 g of agar. Adjust with 0.1 N sodium hydroxide or 0.1 N hydrochloric acid to a pH between 6.5 and 6.6, adjust the volume with water to 1000 mL, and mix. Add approximately 10-mL portions of the solution to culture tubes, place caps on the tubes, and sterilize at 121for 15 minutes. Cool on a slant, and store in a refrigerator. Prepare a stock culture of Pediococcus acidilactici* on a slant of this medium. Incubate at 35for 20 to 24 hours, and store in a refrigerator. Maintain the stock culture by monthly transfer onto fresh slants.Inoculum— Inoculate three 250-mL portions of Modified Pantothenate Medium from a stock culture slant, and incubate at 35for 20 to 24 hours. Centrifuge the suspension from the combined portions, and wash the cells with Modified Pantothenate Medium. Resuspend the cells in sufficient Modified Pantothenate Medium so that a 1:50 dilution, when tested in a 13-mm diameter test tube, gives 80% light transmission at 530 nm. Transfer 1.2-mL portions of this stock suspension to glass ampuls, seal, freeze in liquidnitrogen, and store in a freezer. On the day of the assay, allow the ampuls to reach room temperature, mix the contents, and dilute 1 mL of thawed culture with sterile saline TS to 150 mL. [NOTE—This dilution may be altered, when necessary, to obtain the desired test response. ]Procedure— Prepare in triplicate a series of eight culture tubes by adding the following quantities of water to the tubes within a set: 5.0 mL, 4.5 mL, 4.0 mL, 3.5 mL, 3.0 mL, 2.0 mL, 1.0 mL, and 0.0 mL. To these same tubes, and in the same order, add 0.0 mL, 0.5 mL, 1.0 mL, 1.5 mL, 2.0 mL, 3.0 mL, 4.0 mL, and 5.0 mL of the Standard Preparation.Prepare in duplicate a series of five culture tubes by adding the following quantities of water to the tubes within a set: 4.0 mL, 3.5 mL, 3.0 mL, 2.0 mL, and 1.0 mL. To these same tubes, and in the same order, add 1.0 mL, 1.5 mL, 2.0 mL, 3.0 mL, and 4.0 mL of the Assay Preparation.Add 5.0 mL of Double-Strength Modified Pantothenate Medium to each tube, and mix. Cover the tubes with metal caps, and sterilize in an autoclave at 121 for 5 minutes. Cool to room temperature in a chilled water bath, and inoculate each tube with 0.5 mL of the Inoculum. Allow to incubate at 37for 16 hours. Terminate growth by heating to a temperature not below 80, such as by steaming at atmospheric pressure in a suitable sterilizer, for 5 to 10 minutes. Cool, and concomitantly determine the percentage transmittance of the suspensions, in cells of equal pathlength, on a suitable spectrophotometer, at 530 nm.Calculation— Draw a dose-response curve on arithmetic graph paper by plotting the average response, in percent transmittance, for each set of tubes of the standard curve against the standard level concentrations. The curve is drawn by connecting each adjacent pair of points with a straight line. From this standard curve, determine by interpolation the potency, in terms ofdexpanthenol, of each tube containing portions of the Assay Preparation .Divide the potency of each tube by the amount of Assay Preparation added to it, to obtain the individual responses. Calculate the mean response byaveraging the individual responses that vary from their mean by not more than 15%, using not less than half the total number of tubes. Calculate the potency of the portion of the material taken for assay, in terms of dexpanthenol, by multiplying the mean response by the appropriate dilution factor.* American Type Culture Collection No. 8042 is suitable. Auxiliary Information — Please check for your question in the FAQs before contacting USP.Topic/Question ContactExpert Committee General Chapter Curtis Phinney1-301-816-8540(DSN05) Dietary Supplements - Non-Botanicals ReferenceStandardsLili Wang, Technical Services Scientist1-301-816-8129。

USP纯化水中英文对照

Purified WaterH2O 18.02note—For microbiological guidance, see general information chapter Water for Pharmaceutical Purposes 1231.注意：对于微生物的指导,请参阅医药信息1231章的水章节。

DEFINITION定义» Purified Water is water obtained by a suitable process. It is prepared from water complying with the U.S. Environmental Protection Agency National Primary Drinking Water Regulations or with the drinking water regulations of the European Union or of Japan, or with the World Health Organization's Guidelines for Drinking Water Quality. It contains no added substance.纯化水是通过经过一种经过处理的水。

它的原水是符合美国环境保护署、欧盟、日本国家饮用水条例或世界卫生组织指标的饮用水。

不含任何添加剂。

[NOTE—Purified Water whether it is available in bulk or packaged forms, is intended for use as an ingredient of official preparations and in tests and assays unless otherwise specified (see 8.230. Water under 8. Terms and Definitions in the General Notices and Requirements). Where used for sterile dosage forms, other than for parenteral administration, process the article to meet the requirements under Sterility Tests <71>, or first render the Purified Water sterile and thereafter protect it from microbial contamination. Do not use Purified Water in preparations intended for parenteral administration. For such purposes use Water for Injection, Bacteriostatic Water for Injection, or Sterile Water for Injection. In addition to the Specific Tests, Purified Water that is packaged for commercial use elsewhere meets the additional requirements for Packaging and Storage and Labeling as indicated under Additional Requirements.]注：纯化水可以有散装或灌装（有包装）的两种形式。

USP制药用水介绍_杨仲元

更多GMP资料 (资料来源于互联网)
水的类型
抑菌注射用水-（有正文）是加有一种或多种抑菌剂的灭菌注射用水。作为制备注射用制剂的稀释剂，常用于需要重复抽取的多剂量制剂。可为单剂量包装，也可为多剂量包装，不得大于30ml。灭菌灌洗用水-（有正文）为包装的灭菌的注射用水，规格为大于1L的单剂量容器。[不需符合不溶性微粒检查]，在要用批量注射用水或纯化水时如没有验证了的制水设备或需要量较灭菌注射用水大，且没有微粒要求，也可用灭菌灌洗用水。
更多GMP资料 (资料来源于互联网)
水的类型
由于内毒素是由细菌产生并存在在水中，所以纯化、贮存和输送注射用水的设备和方法应能防止微生物污染，并能除去原水带来的外来内毒素。注射用水设备应经验证，可靠稳定地生产出符合质量要求的注射用水。大包装注射用水应无菌。使用者应保证包装材料应适用于需要更纯的水用于生产、临床和检验的要求。
非正文水
非正文水可能用于制药工艺中，如清洗、合成工序、或进一步纯化的起始原料。本药典中出现的几种非药典正文水如下： [饮用水-称为饮用水、初级饮用水、国家饮用水。除规定标准外，应符合美国环保署的国家初级饮用水的标准，或欧盟、日本、世界卫生组织关于水的规定。] 饮用水可用于制药设备和产品接触部件的初洗，是制备原料药用水的最低质量要求。
更多GMP资料 (资料来源于互联网)
水的类型
血液透析用水-（有正文），用于血液透析，主要用于血液透析浓液的稀释。用符合美国环保署标准并事先纯化的饮用水制备。可以包装在惰性容器中，应能防止微生物进入。 “惰性容器”系指该容器，特别是与水的接触面，不会溶出或由于化学反应产生物质，不会被水腐蚀。血液透析用水不含杀菌剂，不能用于注射。应符合水电导率、总有机碳（或易氧化物）、微生物限度和细菌内毒素检查的规定。水电导率和总有机碳检查与纯化水和注射用水同。有机物含量可用易氧化物检查代替总有机碳。