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USP35-NF-30结构整理vivi2010-10-02USP总目录：1 New Official Text修订文件加快修订过程包括勘误表，临时修订声明（IRAS），修订公告。

勘误表，临时修订声明，修订公告在USP网站上New Official Text部分刊出，勘误表，临时修订公告也会在PF上刊出2front matter前言药典与处方集增补删减情况，审核人员，辅料收录情况3凡例药典，1标题和修订2 药典地位和法律认可3标准复合性4专论和通则5 专论组成6 检验规范和检验方法7 测试结果8 术语和定义9 处方和配药10 包装存储与标签4通则4.1章节列表4.2一般检查和含量测定（章节编号小于1000）检查和含量分析的一般要求检查和含量分析的仪器，微生物检查，生物检查和含量测定，化学检查和含量测定，物理检查和测定4.3一般信息（章节号大于1000）5食物补充剂通则6试剂（试剂，指示剂，溶液等）7参考表性状描述和溶解性查询表（按字母顺序）8食品补充剂各论（字母顺序）9NF各论（辅料标准）10 USP各论11术语附件：通则的章节中文目录（使用起来比较方便，直接找对应章节号即可）一、通用试验和检定（1）试验和检定的总要求1 注射剂11 参比标准物（2）试验和检定的装置16 自动分析方法21 测温仪31 容量装置，如容量瓶、移液管、滴定管，各种规格的误差限度41 砝码和天平（3）微生物学试验51 抗菌效力试验55 生物指示剂：耐受性能试验61 微生物限度试验61 非灭菌制品的微生物检查：计数试验62 非灭菌制品的特定菌检查，如大肠杆菌、金葡菌、沙门氏菌等71 无菌试验（4）生物学试验和检定81 抗生素微生物检定85 细菌内毒素试验87 体外生物反应性试验：检查合成橡胶、塑料、高聚物对哺乳类细胞培养的影响88 体内生物反应性试验：检查上述物质对小鼠、兔iv、ip或肌内植入的影响91 泛酸钙检定111 生物检定法的设计和分析115 右泛醇检定121 胰岛素检定141 蛋白质——生物适应试验，用缺蛋白饲料大鼠，观察水解蛋白注射液和氨基酸混合物的作用151 热原检查法161 输血、输液器及类似医疗装置的内毒素、热原、无菌检查171 维生素B12 活性检定（5）化学试验和检定A 鉴别试验181 有机含氮碱的鉴别191 一般鉴别试验193 四环素类鉴别197 分光光度法鉴别试验201 薄层色谱鉴别试验B 限量试验206 铝211 砷221 氯化物和硫酸盐223 二甲基苯胺226 4-差向脱水四环素231 重金属241 铁251 铅261 汞271 易炭化物试验281 炽灼残渣291 硒C 其他试验和检定301 中和酸能力311 藻酸盐检定331 苯丙胺检定341 多剂量容器注射剂中所加防腐剂含量的气相色谱或极谱法测定345 枸橼酸与其盐以及磷酸盐检定351 甾体检定361 巴比妥酸盐检定371 维生素B12放射示踪物检定381 注射剂橡胶塞检查391 肾上腺素检定401 脂肪和固定油检查411 叶酸检定425 抗生素碘量法检定429 微粒大小的光衍射测量431 甲氧基测定441 烟酸或烟酰胺检定451 亚硝酸盐滴定461 氮测定466 普通杂质的薄层色谱法检查467 有机挥发性杂质检查法467 残留溶剂测定471 氧瓶燃烧法481 核黄素检定501 有机含氮碱的盐511 单一甾醇检定521 磺胺类的色谱法检定531 硫胺检定541 滴定法554 α-生育酚检定561 植物来源物品的一般检查项目563 植物来源物品的各种鉴别项目（植物学部分、显微鉴别、化学鉴别）565 植物提取物的一般提取方法和要求571 维生素A检定：化学法、色谱法581 维生素D检定：色谱法、化学法、生物法591 锌测定（6）物理试验和测定601 气雾剂、鼻喷雾剂、计量吸入剂和干粉吸入剂的各项检测611 乙醇含量测定：蒸馏法、气一液色谱法616 固体的疏松密度和叩击密度测定621 色谱法631 色度检查和标准641 溶解的完全性检查643 总有机炭测定645 水导电性测定651 冻凝温度的测定661 药用容器的检测项目要求671 盛装胶囊和片剂容器加盖后对湿气的通透性试验691 棉花吸附性和纤维长度测定695 结晶性检查696 用溶液测热法测定结晶度698 装量检查699 固体密度（粉粒密度测定法）701 崩解试验711 溶出试验721 蒸馏温度范围（馏程）测定724 通过透皮转运系统药物的释放726 电泳727 毛细管电泳730 等离子体光谱化学检查法731 干燥失重733 炽灼失重736 质谱法741 熔点范围或温度的测定751 眼膏中的金属颗粒测定755 最低装量检查法761 核磁共振771 眼用软膏的要求776 光学显微镜微粒检查法781 旋光度检查785 渗透压摩尔浓度测定法786 用分析筛测量颗粒大小的分布788 注射液中微粒物质测定法789 眼用溶液中微粒物质测定法791 PH测定法795 非灭菌制剂的药物配制要求797 灭菌制剂的药物配制要求801 极谱法811 粉末细度测定821 放射活性药物823 正电子发射层析X线摄影（PET）所用放射性药物的配制831 折光指数测定841 比重测定846 粉末的比表面积测定851 分光光度法与光散射861 外科缝合线直径检查871 附有针的缝合线检查881 外科缝合线、纺织品与膜片的弹力强度检查891 热分析：温度变化、热解重量分析、易熔杂质分析等905 剂量单位的均匀性检查（含量均匀度、装量差异）911 黏度测定921 药品含水量的测定941 结晶型药物的X线衍射分析二、通用资料1010 数据分析方法1015 诊断用放射药的自动合成装置1031 药用容器、医用装置和植入物所用材料的生物相容性检查1035 灭菌用生物指示剂1041 生物制品的批签发1043 细胞、基因和组织工程产品的辅助材料1045 生物技术产品1046 细胞和基因治疗产品1047 生物技术产品的检验法1048 生物技术产品的质量——重组DNA蛋白质产品生产所用细胞表达构成的分析1049 生物技术产品的稳定性试验1050 人或动物来源的细胞系所得生物技术产品的病毒安全性评价1051 玻璃仪器清洗方法1061 颜色的仪器测量1065 离子色谱1072 消毒剂与防腐剂1074 赋形剂生物学安全性评价指导原则1075 复方药物配制质量规范1078 大批量药用赋形剂的生产质量规范1079 储存与运输的质量规范1081 明胶的凝胶强度1086 药品中的杂质来源1087 特性溶出1088 剂型的体外和体内评价1090 体内生物等效性试验指导原则1091 剂型中含有无活性组分的标示1092 溶出试验方法的发展和验证1101 药用滴管1111 非灭菌药品的微生物特征1111 非灭菌药品的微生物特征检查：药用原料和药物制剂的判定标准1112 非灭菌药品中的水活性测定，即在同一温度时，药品中水的蒸气压与纯水蒸气压之比，它等于药品在密闭系统中产生相对湿度的1%1116 清洁室和其他受控环境的微生物评价1117 微生物实验室的质量规范（GLP）1118 监控装置：时间、温度、湿度1119 近红外分光光度法1120 拉曼（Raman）分光光度法1121 药品命名法1136 药品包装：应用单元1146 口服固体药分装在单疗程剂量容器中的检查方法1150 药物剂型的稳定性1151 药物剂型1160 处方调配的药学计算1171 原料药的位相溶解度分析1174 粉末流动性测定1176 处方天平和容量装置1177 包装质量规范1178 分装质量规范1181 扫描电子显微镜1191 调剂工作中的药品稳定性保持1196 药典协调（指欧洲药典、美国药典、日本药局方三方机构讨论协调的原则和方法）1207 灭菌产品包装：完整性评价1208 灭菌试验：隔离系统的验证1209 灭菌：化学和物理化学的指示剂与积分仪1211 药典收载品种的灭菌和灭菌保证1216 片剂脆性检查1221 茶匙（家用标准为5 ml，可作为病人口服液体药物的量具，误差应小于10%）1222 药品灭菌终点的放行参数1223 微生物替代方法的验证1225 药典方法的验证1227 在抗菌效力、微生物限度、灭菌等试验中，微生物的恢复验证1230 血液透析用水1231 药用水的制备和要求1241 在制药系统中，水—固体的相互作用1251 用分析天平称量的要求1265 书写药物处方的指导原则三、饮食增补剂2021 营养和饮食增补剂的微生物计数试验2022 营养和饮食增补剂中不允许存在的微生物（如金葡菌、沙门氏菌、大肠杆菌、梭状芽胞杆菌属）检查法2023 非灭菌的营养和饮食增补剂中的微生物特征2030 植物来源物品的增补资料2040 饮食增补剂的崩解和溶出检查2091 饮食增补剂的重（装）量差异检查2750 饮食增补剂的生产条件与质量要求（与药品有别）。

09 USP35盐酸丁丙诺啡质量标准(译文)

盐酸丁丙诺啡（USP35译文）C29 H42ClNO4504.16,14-亚乙烯基吗啡喃-7-甲醇；17-（环丙基-甲基）-α-（1,1-二甲基乙基）-4,5-环氧-18,19-二氢基-3-羟基-6-甲氧基-α-甲基，盐酸盐；[5α,7α(S)]-21-环丙基-7α- [(S)-1-羟基-1,2,2-3甲基丙基]-6,14-内-亚乙烯基-6,7,8,14-四氢东罂粟碱盐酸盐。

盐酸丁丙诺啡的含量不少于98.5%，不得过101.0%,以干燥品计算。

包装与贮存---保存于密闭、避光的容器中。

USP参照标准（11）---USP盐酸丁丙诺啡RSUSP丁丙诺啡相关物质A RS21-[3-(1-丙烯基)]-7α-[ (S)-1-羟基-1,2,2-三甲基-丙基]-6，14-亚乙烯基-6,7,8,14-四氢东罂粟碱。

C29H41NO4467.65鉴别—A:红外吸收（197K）。

B:向0.5ml 50mg/ml 盐酸丁丙诺啡甲醇溶液中加入0.2ml新配制的铁氰化钾TS 准备溶液（1:10）和0.5ml的三氯化铁TS溶液：立即呈现蓝色。

C:溶液（1:100）符合氯化物检测要求（191）。

比旋度（781S）:-92°~-98°。

测试溶液：20mg/ml的甲醇溶液。

pH（791）:4.0~6.0（溶液浓度为10mg/ml）。

水分：方法1（921）：不超过1.0%。

炽灼残渣（281）：不超过0.1%。

色谱纯度—流动相—准备已过滤和脱气的甲醇：1%的乙酸铵溶液：冰醋酸（60:10:0.01）的混合液，如果需要可做调整【见色谱（621）系统适用性】。

标准溶液—精密称量USP盐酸丁丙诺啡RS与USP丁丙诺啡相关物质A RS，加流动相制备两种物质浓度均为12.5ug/ml的混合溶液。

测试溶液—精密称量50mg的盐酸丁丙诺啡，加10ml流动相，制备浓度为5mg/ml的溶液。

色谱系统【见色谱（621）】—液相色谱检测器的检测波长为288nm，4.6m m ×250mm、填料为L1的色谱柱，流速为1ml/min，柱温：40℃。

布地奈德USP35检验操作规程

布地奈德 USP35 检验操作规程
含量测定（HPLC）：溶液配制磷酸盐缓冲液：3.17mg/mL 磷酸二氢钠和 0.23mg/mL 磷酸混合溶液。pH 值为 3.2±0.1 流动相：乙腈 – 磷酸盐缓冲液（32:68 V/V）对照品溶液：称取适量布地奈德 USP 标准品溶解于乙腈，用适量的磷酸盐缓冲液稀释，得到的溶液含布地奈德 0.5mg/mL，溶液中乙腈的含量不得过 30%。样品溶液：称取 25mg 样品于 50mL 容量瓶中，用 15mL 乙腈稀释，再用磷酸盐缓冲液稀释定容至刻度。液相色谱条件（参考色谱法<621>，系统适应性）检测器：UV254nm 色谱柱：4.6mm×15cm；5μm packing L1 流速：1.5mL/min 进样量：20μL 系统适应性对照品溶液中差向异构体 A 的相对保留时间为 1.1（相对于差向异构体 B）。系统适应性要求：分离度：布地奈德两差向异构体峰的分离度不得低于 1.5 柱效：按照布地奈德差向异构体 B 峰计算，不得低于 5500 理论塔板数。含量分析分析对象：对照品溶液、样品溶液布地奈德差向异构体 A（C25H3406）含量百分比计算
可接受标准布地奈德差向异构体 A：40.0% ~ 51.0%，以干品计。布地奈德（含差向异构体 A、差向异构体 B）：98.0% ~ 102.0%，以干品计。
有关物质测定（HPLC）
检测方法 1：布地奈德杂质 21-acetate 含量限制溶液配制磷酸盐缓冲液：3.17mg/mL 磷酸二氢钠和 0.23mg/mL 磷酸混合溶液。pH 值为 3.2±0.1 流动相：乙腈 – 磷酸盐缓冲液（45:55 V/V）对照品溶液：称取适量布地奈德 USP 标准品溶解于乙腈，用适量的磷酸盐缓冲液稀释，得到的溶液含布地奈德 0.5mg/mL，溶液中乙腈的含量不得过 30%。样品溶液：称取 25mg 样品于 50mL 容量瓶中，用 15mL 乙腈稀释，再用磷酸盐缓冲液稀释定容至刻度。液相色谱条件（参考色谱法<621>，系统适应性）检测器：UV254nm 色谱柱：4.6mm×15cm；5μm packing L1 流速：1.5mL/min 进样量：20μL 系统适应性对照品溶液第一次洗脱的布地奈德杂质 21-acetate 差向异构体相对保留时间为 3.1；对照品溶液第二次洗脱的布地奈德杂质 21-acetate 差向异构体相对保留时间为 3.2；对照品溶液第一次洗脱的布地奈德差向异构体 B 相对保留时间为 1.0；对照品溶液第一次洗脱的布地奈德差向异构体 A 相对保留时间为 1.1。系统适应性要求柱效：按照布地奈德差向异构体 B 峰计算，不得低于 5500 理论塔板数。样品溶液分析布地奈德杂质 21-acetate 含量百分比计算

常用药物制剂方法

制剂处方1。

氨茶碱注射液取计算量重的茶碱加入二乙胺，使其生成氨茶碱，加入注射用水，PH应为8.6–9.0，每毫升含二水合氨茶碱为23.56–26.75mg，每克二水合氨茶碱含乙二胺为131–152mg。

检验合格后，经过滤澄明、粉装、灭菌即得。

氨茶碱在剧烈搅拌下将茶碱加入含有等摩尔的乙二胺的无水乙醇中，数小时后，滤取沉淀，用冷乙醇洗涤，在低温下干燥即得氨茶碱。

兽医人技术联盟_中国专业兽医人的技术交流平台2。

安痛定滴鼻液氨基比林5.0g，安替比林2.0g，巴比妥0.9g，乙二胺四乙酸二钠（EDTA–2Na）0.02g，月桂醇硫酸钠0.01g，蒸馏水加至100ml,常法制备而得。

3。

保泰松外用香膏剂保泰松5g，二甲基亚砜10g，硬脂酸2g，乙二醇棕榈酸硬脂酸酯12g，甘油5g，杏仁油5g，水100g，抗氧剂与香精适量，常法制成膏剂即得。

4。

缓释硫酸阿托品片硫酸阿托品1.6g，CaHPO4 158.04g，70%二醛淀粉浆10.0g，25%乙基甲基纤维素液15.0g，混合均匀后用无水乙醇50ml制粒，常法制成片剂即得。

兽医教学参考,兽医临床交流,犬病辅助诊断系统5。

肠溶阿司匹林片用羟丙基甲基纤维素邻苯二甲酸酯与乙基纤维素（用量为前者的15-20%）混合液包肠溶衣，在pH4.5的缓冲液中阿司匹林即开始释放，崩解时限仅30s。

动物医学论坛5O.m8W;t;S+b-h 6。

阿司匹林微囊①取阿司匹林结晶粉20g混悬于乙基纤维素（1.5g）的醋酸乙酯溶液中，再将此混悬溶液搅拌分散于聚乙烯醇（3g）的水溶液中，加适量水稀释，在不断搅拌下蒸发除去醋酸乙酯，即得阿司匹林微囊（直径0.6–0.8mm）。

②将乙基纤维素溶于醋酸乙酯中，取阿司匹林（直径<300μm）混悬于前述溶液中，将此混悬液倾入聚样乙烯氢化蓖麻油中，然后将混合液喷雾干燥，使醋酸乙酯挥发，得阿司匹林微囊，再按一般工艺压片。

成品在人工胃液中释放缓慢。

7。

不同HPLC测定方法测定氨磷汀及其相关物质的比较

不同HPLC测定方法测定氨磷汀及其相关物质的比较陶竞;李婵娟;卢山【摘要】目的比较中国卫生部及美国药典(USP35)颁布的氨磷汀及其相关物质的高效液相(HPLC)测定方法.方法美国药典USP35测定方法采用C8色谱柱,流动相采用7∶18(甲醇∶0.94g/L己烷磺酸)溶液,检测波长为220nm,流速1.0mL/min;中国卫生部的标准采用C18色谱柱,流动相采用1∶1(甲醇∶3.5mmol/L辛烷磺酸钠)溶液,检测波长均为220nm,流速0.7 mL/min.结果两种方法检测氨磷汀及相关物质都符合对杂质的要求.结论美国药典USP35的检测方法对氨磷汀及相关物质检测的质量控制更好.【期刊名称】《标记免疫分析与临床》【年(卷),期】2015(022)002【总页数】3页(P142-144)【关键词】高效液相;氨磷汀;美国药典【作者】陶竞;李婵娟;卢山【作者单位】武汉大学中南医院药学部,湖北武汉430071;湖北省中山医院药学部,湖北武汉430000;武汉晟辉生物医药科技有限公司,湖北武汉430040【正文语种】中文氨磷汀(amifostine)又名 WR-2721，结构式为NH2-(CH2)3-NH-(CH2)2-S-PO3H2。

是美国食品和药物管理局第一个批准上市的细胞保护剂，是用于肿瘤放疗及细胞毒性化疗的辅助药物［1］，能保护正常细胞免受放疗及化疗的毒性损伤又不干扰抗肿瘤活性，且毒性小，能显著改善肿瘤患者对化疗及放疗的耐受性，提高患者的生存质量。

基于氨磷汀重要的药用价值，对药物中氨磷汀含量进行准确的测定就显得尤为重要。

目前对氨磷汀及相关物质的检测方法有 HPLC-紫外测定法及 HPLC-电化学测定法［2-4］。

由于氨磷汀化学性质极为活跃，且代谢物WR-1065与本体色谱学特性不同，需要在上机检测前将氨磷汀转化为WR-1065进行检测，加大了检测结果的误差，延长了检测时间［5-11］。

为了提高氨磷汀的检测质量控制标准，本文对美国药典USP35及我国卫生部颁布的检测标准进行了对比。

usp美国药典结构梳理

USP35-NF-30结构整理vivi2010-10-02USP总目录：1 New Official Text修订文件加快修订过程包括勘误表，临时修订声明（IRAS），修订公告。

安瓿瓶质量标准USP35文件

玻璃容器用于医药用途的玻璃容器都是与药物制剂直接接触的。

制作医药容器的玻璃一般都是硼硅酸盐玻璃（中性）或者是钠钙玻璃。

硼硅酸盐玻璃含有一定量的氧化硼，氧化铝，碱金属或者碱土金属氧化物。

由于玻璃本身的化学组成，硼硅酸盐玻璃具有较高的耐水解性，被分类为Ⅰ型玻璃。

钠钙玻璃是含有碱金属氧化物的石英玻璃，由于其自身的化学组成成分，它具有适度的耐水解性，被分类为Ⅲ型玻璃。

玻璃容器的内表面可以经过处理，比如提高它的耐水解性。

Ⅲ型的钠钙玻璃容器经过处理后，可能会将其本身的耐水解性由中等水平提升到较高水平，从而被归类为Ⅱ型玻璃。

玻璃容器的外表面经过处理后，可能会减小它的摩擦力，或者防止它的磨损或破损程度。

外表面的处理不会接触到容器的内表面。

玻璃可以上色或者对外表面进行涂层，从而达到避光的效果。

这样的玻璃容器将要符合容器性能测试中的光传输要求<671>。

无色透明或半透明的容器可以通过用不透明外壳（参见凡例中的耐光容器的保留，包装，储存和贴标）来包装，从而达到光传输的要求，达到避光的效果。

玻璃容器质量的好坏是通过测定它们的耐化学腐蚀性来定义的。

此外，用于包装非肠道药品的Ⅰ型玻璃需要测定砷释放程度，有色玻璃需要测定透光性。

耐化学性对新的玻璃容器（以前没有用过的）需要进行耐水蚀的试验。

侵蚀的程度取决于在规定条件下因侵蚀物的作用而释放出的碱的含量。

如果是非常耐腐蚀的玻璃，碱释放量极少。

因而需要特别注意测试的过程和使用精巧的装置。

测试应在相对来说不受烟雾灰尘影响的地方进行。

玻璃类型——适合于包装药品制剂的玻璃容器的类型可在表 1 中看到。

Ⅰ型硼硅酸盐玻璃容器常被用来包装非肠道药品。

Ⅰ型玻璃，或Ⅱ型玻璃（比如适度脱碱的钠钙玻璃）常被用于包装酸性或中性非肠道药品。

Ⅰ型玻璃容器，或者Ⅱ型玻璃容器（其稳定性数据证明可适用性）被用于碱性非肠道药品。

Ⅲ型钠钙玻璃容器通常不用于非肠道药品，除非其稳定性试验数据显示可以适用。

表1. 玻璃类型类型概述测试类型Ⅰ高耐磨，硼硅酸盐玻璃玻璃粉Ⅱ处理后的钠钙玻璃水蚀Ⅲ钠钙玻璃玻璃粉仪器——高压灭菌锅——在这些测试中使用的高压灭菌锅，必须能将温度保持在121± 2.0 ℃，配有温度计，压力计和气阀，能够一次容纳至少12 个测试样品。

布地奈德USP35检验操作规程

含量百分比=(rT1+rT2)×100
rT1：布地奈德溶液中杂质 21-acetate 两个差向异构体的峰面积总和； rT2：布地奈德溶液中布地奈德两个差向异构体的峰面积总和；
可接受标准布地奈德杂质 21-acetate 含量不得过 0.10%
检测方法 2：布地奈德杂质 11-ketobudesonide 含量限制溶液配制磷酸盐缓冲液：3.17mg/mL 磷酸二氢钠和 0.23mg/mL 磷酸混合溶液。pH 值为 3.2±0.1 流动相：乙腈 – 异丙醇 – 磷酸盐缓冲液（26:9:65 V/V/V）对照品溶液：称取适量布地奈德 USP 标准品溶解于乙腈，用适量的磷酸盐缓冲液稀释，得到的溶液含布地奈德 0.5mg/mL，溶液中乙腈的含量不得过 30%。样品溶液：称取 25mg 样品于 50mL 容量瓶中，用 15mL 乙腈稀释，再用磷酸盐缓冲液稀释定容至刻度。液相色谱条件（参考色谱法<621>，系统适应性）检测器：UV254nm 色谱柱：4.6mm×15cm；5μm packing L1 柱温：50°C 流速：1.5mL/min 进样量：20μL 系统适应性对照品溶液 11-ketobudesonide 两个差向异构体的相对保留时间分别为 0.73 和 0.78； 21-dehydrobudesonide，14,15- dehydrobudesonide，第一次洗脱的布地奈德差向异构体 B 的相对保留时间分别为 0.68, 0.84, 1.0。系统适应性要求柱效：按照布地奈德差向异构体 B 峰计算，不得低于 5500 理论塔板数。样品溶液分析布地奈德杂质 21-acetate 含量百分比计算
相对保留时间 0.11 0.36
0.61; 0.66
0.86 — — —

USP35头孢唑林钠

缓冲液 A：乙腈-6.8mg/ml 磷酸二氢钾溶液(50:50)
溶液 B：6.8mg/ml 磷酸二氢钾溶液(用 10%氢氧化钠溶液调 pH 值至 6.8)
溶液 C：乙腈-缓冲液 A（1:1）
流动相：见表 1。
表1
时间(分钟)
溶液 B(%)
溶液 C(%)
0
98
2
7
98
2
15
85
15
30
80
20
35
80
表表2代号名称检测波长nm相对保留时间校正因子f可接受标准不得过10a四氮唑乙酸n22二羟乙基21h四唑1基乙酰胺头孢唑林开环内酯林3羟甲基e甲基噻重氮硫醇7氨基头孢菌酸210007040b21000803310cd或头孢唑2540201005fg2542540230420911110104hijklmn头孢唑林3甲基类似物头孢唑林内酯头孢唑林乙酰氧基类似物脱酰头孢唑林头孢唑林开环异构体头孢唑林头孢唑林异构体头孢唑林特戊酰其他单个杂质总杂254254254254254254254254254044050061068084101214087085068121009809210101010100510100135杂质a
1
系统要求
分离度：分析物峰与水杨酸峰间分离度不得少于 4.0。柱效：理论板数不得少于 1500 拖尾因子：不得大于 1.5 相对偏差：不得大于 2.0% 分析
样品：标准溶液和样品溶液
计算头孢唑林钠（C14H14NaN8O4S3）百分含量：结果=（RU/RS）×（CS/CU）×（Mr1/ Mr2）×100 式中：
20
45
50
50
50
50
50
55
98

USP35奥氮平片美国药典35版质量标准

USP 35Official Monographs / Olanzapine 4105USP Fluoxetine Related Compound B RS r S = peak response from the Standard solution N -Methyl-3-phenylpropylamine.C S= concentration of USP Olanzapine RS in theC 10H 15N 149.23Standard solution (mg/mL)USP Olanzapine RSC U = concentration of olanzapine in the Sample10H -Thieno[2,3-b ][1,5]benzodiazepine, 2-methyl-4-(4-solution (mg/mL)methyl-1-piperazinyl.Acceptance criteria: 90.0%–110.0%C 17H 20N 4S 312.43PERFORMANCE TESTS USP Olanzapine Related Compound B RS•D ISSOLUTION 〈711〉2-Methyl-10H -thieno-[2,3-b ][1,5]benzodiazepin-4[5H ]-one.Medium: 0.1 N hydrochloric acid; 900 mL C 12H 10N 2OS 230.29Apparatus 2: 50 rpm Time: 30 minMobile phase: 10g/L of ammonium acetate in a mixture of methanol and water (2:3). Adjust with hydrochloric acid to a pH of 4.0.Olanzapine TabletsStandard solution: An amount, in mg, corresponding to the Tablet label claim, of USP Olanzapine RS in 1000 mL of DEFINITIONMedium . Transfer 5.0 mL of this solution to a tube, and add Olanzapine Tablets contain NLT 90.0% and NMT 110.0% of 2.0 mL of Mobile phase .the labeled amount of olanzapine (C 17H 20N 4S).Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Transfer 5.0IDENTIFICATIONmL of the filtrate to a tube, and add 2.0 mL of Mobile phase .•I NFRARED A BSORPTION 〈197S 〉Chromatographic systemStandard solution: 1 mg/mL of USP Olanzapine RS in (See Chromatography 〈621〉, System Suitability .)chloroformMode: LCSample solution: Dissolve a quantity of powdered Tablets,Detector: UV 260 nmequivalent to 30 mg of olanzapine, in 30 mL of chloroform,Column: 4.6 mm × 15 cm; 5-µm packing L10and filter. Evaporate completely to dryness with the aid of a Flow rate: 1.5 mL/min current of air. Redissolve the residue in 1 mL of chloroform.Injection size: 50 µL ASSAYSystem suitability•P ROCEDURESample: Standard solution Buffer 1: 6.9 g/L of monobasic sodium phosphate. Adjust Suitability requirementswith phosphoric acid to a pH of 2.5.Relative standard deviation: NMT 2.0%Buffer 2: 12g/L of sodium dodecyl sulfate in Buffer 1AnalysisMobile phase: Acetonitrile and Buffer 2 (1:1)Calculate the percentage of olanzapine dissolved:System suitability solution: 0.1 mg/mL of USP Olanzapine Result = (r U /r S ) × (C S × V/L) × 100RS and 0.01 mg/mL of USP Olanzapine Related Compound A RS in Mobile phaser U = peak response from the Sample solution Standard solution: 0.1 mg/mL of USP Olanzapine RS in Mo-r S = peak response from the Standard solution bile phaseC S= concentration of USP Olanzapine RS in theSample solution: Transfer a known quantity of Tablets,Standard solution (mg/mL)equivalent to NLT 25 mg of olanzapine, to a suitable volu-V = volume of Medium , 900 mL metric flask. Dilute with Mobile phase to volume, mix, and L = label claim (mg/Tablet)sonicate for 10 min. Centrifuge a portion of this solution,Tolerances: NLT 80% (Q) of the labeled amount of and dilute the clear supernatant with Mobile phase to obtain olanzapine is dissolved.a solution containing about 0.1 mg/mL of olanzapine.•U NIFORMITY OF D OSAGE U NITS 〈905〉: Meet the requirements [N OTE —Agitation of the flask may be necessary before soni-cation to prevent Tablets from adhering to the flask, making IMPURITIESdisintegration and dissolution difficult.]Organic Impurities Chromatographic system•P ROCEDURE(See Chromatography 〈621〉, System Suitability .)Buffer 1: 3.3 mL/L of phosphoric acid. Adjust with 50%Mode: LCNaOH to a pH of 2.5.Detector: UV 260 nmBuffer 2: 8.7 g/L of sodium dodecyl sulfate in Buffer 1Column: 4.6-mm × 15-cm; 5-µm packing L7Buffer 3: 18.6 mg/L of edetate disodium (EDTA) in Buffer 2Flow rate: 1.5 mL/min Solution A: Acetonitrile and Buffer 2 (12:13)Injection size: 20 µL Solution B: Acetonitrile and Buffer 2 (7:3)System suitabilityDiluent: Acetonitrile and Buffer 3 (2:3)Samples: System suitability solution and Standard solution System suitability solution: 20 µg/mL of USP Olanzapine [N OTE —The relative retention times for olanzapine related RS, and 2 µg/mL each of USP Olanzapine Relatedcompound A and olanzapine are 0.89 and 1.0,Compound B RS and USP Olanzapine Related Compound respectively.]C RS in DiluentSuitability requirementsStandard solution: 2 µg/mL of USP Olanzapine RS in Resolution: NLT 2.0 between olanzapine and olanzapine Diluentrelated compound A, System suitability solution Sensitivity solution: 0.4 µg/mL of USP Olanzapine RS in Tailing factor: NMT 1.8, Standard solutionDiluent , from the Standard solutionRelative standard deviation: NMT 2.0%, Standard Sample solution: Transfer a known quantity of Tablets to a solution suitable volumetric flask, and dilute with Diluent to volume Analysisto obtain a solution containing either 375 or 500 µg/mL of Samples: Standard solution and Sample solutionolanzapine (based on the label claim). Centrifuge a portion Calculate the percentage of C 17H 20N 4S in the portion of of this solution, and use the supernatant. [N OTE —Tablets taken:Immediate agitation of the flask may be necessary to prevent Tablets from adhering to the flask, making Result = (r U /r S ) × (C S /C U ) × 100r U= peak response from the Sample solution4106Olanzapine / Official Monographs USP 35dissolution and disintegration difficult. [Caution—Do not Impurity Table 1 (Continued)sonicate.] The Sample solution is stable for 12 h at room Relative Relative Acceptance temperature and 48 h if refrigerated.]Retention Response Criteria, Mobile phase: See the gradient table Time Factor NMT (%)Olanzapine 1.0——Time Solution A Solution B Any individual— 1.00.20 (min)(%)(%)unspecified impurity01000a(Z)-4-(4-Methylpiperazin-1-yl)-3-(2-oxopropylidene)-1H-benzo[b][1,4] 101000diazepin-2(3H)-one.200100b2-Methyl-10H-thieno-[2,3-b][1,5] benzodiazepin-4[5H]-one.250100c(Z)-1-{4-(4-Methylpiperazin-1-yl)-2-thioxo-1H-benzo[b][1,4]diazepin-3(2H)-ylidene}propan-2-one.271000d2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4] 351000diazepine 4’-N-oxide.Chromatographic system ADDITIONAL REQUIREMENTS(See Chromatography 〈621〉, System Suitability.)•PACKAGING AND S TORAGE: Preserve in tight, light resistant Mode: LC containers, and store at controlled room temperature.Detector: UV 220 nm•USP REFERENCE S TANDARDS〈11〉Column: 4.6-mm × 25-cm; 5-µm packing L7USP Olanzapine RSTemperature: 35°USP Olanzapine Related Compound A RSFlow rate: 1.5 mL/min5-Methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile.Injection size: 20 µL USP Olanzapine Related Compound B RSSystem suitability2-Methyl-10H-thieno-[2,3-b][1,5]benzodiazepin-4[5H]-one.Samples:System suitability solution, Standard solution,USP Olanzapine Related Compound C RSand Sensitivity solution(2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno Suitability requirements[2,3-e][1,4]diazepine 4′-N-oxide).Resolution: NLT 3.0 between olanzapine and C17H20N4OS328.43olanzapine related compound C, System suitabilitysolutionTailing factor: NMT 1.5 for the olanzapine peak, Systemsuitability solutionRelative standard deviation: NMT 2.0%, Standard Olopatadine HydrochloridesolutionSignal-to-noise ratio: NLT 10, Sensitivity solutionAnalysisSamples:Standard solution and Sample solutionCalculate the percentage of each impurity in the portionof Tablets taken:Result = (r U/r S) × (C S/C U) × (1/F) × 100r U= peak response of each impurity from the SamplesolutionC21H23NO3·HCl373.87 r S= peak response from the Standard solutionDibenz[b,e]oxepin-2-acetic acid, 11-[3-(dimethyl-C S= concentration of USP Olanzapine RS in theamino)propylidene]-6,11-dihydro-, hydrochloride, (Z)-;Standard solution (µg/mL)11-[(Z)-3-(Dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]C U= concentration of olanzapine in the Sampleoxepin-2-acetic acid, hydrochloride [140462-76-6].solution (µg/mL)F= relative response factor for each impurity listed DEFINITIONin Impurity Table 1Olopatadine Hydrochloride contains NLT 98.0% and NMT Acceptance criteria102.0% of C21H23NO3·HCl, calculated on the dried basis.Individual impurities: See Impurity Table 1.Total impurities: NMT 1.5%IDENTIFICATION•A. I NFRARED A BSORPTION〈197K〉•B. The retention time of the major peak of the Sample solu-Impurity Table 1tion corresponds to that of the Standard solution, as obtained Relative Relative Acceptance in the Assay.Retention Response Criteria,•C. I DENTIFICATION T ESTS—G ENERAL, Chloride〈191〉: Meets the Name Time Factor NMT (%)requirementsOlanzapine lactam a0.26 1.00.50ASSAYOlanzapine related0.30 2.30.20•P ROCEDUREcompound B b[N OTE—Protect solutions from light.]Olanzapine thiolactam c0.34 1.00.50Buffer: Dissolve 13.6 g of monobasic potassium phosphate Olanzapine related0.83 1.00.50in 1 L of water, add 1 mL of triethylamine, and mix. Adjust compound C dwith phosphoric acid to a pH of 3.0.a(Z)-4-(4-Methylpiperazin-1-yl)-3-(2-oxopropylidene)-1H-benzo[b][1,4]Mobile phase: Acetonitrile and Buffer (7:18)diazepin-2(3H)-one.Standard solution: 0.1 mg/mL of USP Olopatadine Hydro-b2-Methyl-10H-thieno-[2,3-b][1,5] benzodiazepin-4[5H]-one.chloride RS in Mobile phasec(Z)-1-{4-(4-Methylpiperazin-1-yl)-2-thioxo-1H-benzo[b][1,4]diazepin-Sample solution: 0.1 mg/mL of Olopatadine Hydrochloride 3(2H)-ylidene}propan-2-one.in Mobile phased2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine 4’-N-oxide.。

盐酸多奈哌齐USP35质量标准翻译稿(精)

盐酸多奈哌齐USP35质量标准（中文译稿）盐酸多奈哌齐分子式：C24H29NO3·HCL 分子量：415.95化学名：（±）-2-[（1-苄基-4-哌啶）甲基]-5,6-二甲氧基-1-茚酮盐酸盐[120011-70-3] 含量：盐酸多奈哌齐按干燥品计算，含C24H29NO3·HCL为98%~102%。

[鉴别]A、红外吸收〈197k〉[注意事项—如果样品和对照品在原有固体形态下红外图谱检测结果不一致，则需将样品和对照品分别溶于二氯甲烷中，蒸干溶剂后再进行检测，并记录新的红外谱图进行比较。

]B、在含量测定项下记录的色谱图中，供试品溶液主峰的保留时间应与对照品溶液主峰的保留时间一致。

C、氯化物鉴别〈191〉样品溶液：10mg/ml接受标准：符合要求[含量测定]溶液制备：缓冲液：3.9g/L癸烷磺酸钠水溶液流动相：乙腈：缓冲溶液=35：65，用高氯酸调pH至1.8系统适应性溶液：取USP盐酸多奈哌齐对照品和USP盐酸多奈哌齐有关物质A对照品适量臵容量瓶中，加入容量瓶体积40%的甲醇使溶解，加水稀释至刻度，制成每1ml中含USP盐酸多奈哌齐对照品0.4mg，含USP盐酸多奈哌齐有关物质A对照品0.016mg的溶液。

对照品溶液：用流动相配制成浓度为0.4mg/ml的USP盐酸多奈哌齐对照品盐酸多奈哌齐USP35质量标准（中文译稿）溶液。

供试品溶液：用流动相配制成浓度为0.4mg/ml的盐酸多奈哌齐样品溶液。

色谱条件（见色谱〈621〉，系统适应性）：检测方法：LC（液相色谱法）检测器：紫外检测，波长271nm色谱柱：4.6mm×15cm；填料为L1（十八烷基硅烷键合硅胶）粒径为5μm 柱温：35℃流速：1.4ml/min进样量：20μl系统适应性：进样溶液：系统适应性溶液和对照品溶液[注意事项：参照有机杂质检测方法1中，表1中所述的相对保留时间] 适应性要求：分离度：系统适应性溶液中，多奈哌齐相关物质A和多奈哌齐分离度不得小于1.5相对标准偏差（RSD）：对照品溶液，不得大于2.0%测定法：进样溶液：对照品溶液和供试品溶液计算检验样品中盐酸多奈哌齐（C24H29NO3·HCL）的百分含量检测结果=（ru/rs）×(cs/cu) ×100ru = 供试品溶液中盐酸多奈哌齐的峰面积rs = 对照品溶液中盐酸多奈哌齐的峰面积Cs = 对照品溶液中USP盐酸多奈哌齐对照品的浓度（mg/ml）Cu = 供试品溶液中盐酸多奈哌齐的浓度（mg/ml）接受标准：98%~102%（按干燥品计算）[杂质]重金属：方法Ⅱ〈231〉不得大于20ppm炽灼残渣〈281〉：不得大于0.1%有机杂质：（方法1）盐酸多奈哌齐USP35质量标准（中文译稿）[注意事项：基于合成路线的不同，可以选择方法1和方法2中的一种方法进行有机杂质的检测。

USP35奥氮平原料质量标准

4102Ointment / Official MonographsUSP 35Packaging and storage—Preserve in well-closed containers.Mode: LCDetector: UV 260 nmColumn: 4.6-mm × 15-cm; 5-µm packing L7Flow rate: 1.5 mL/min Injection size: 20 µL Yellow OintmentSystem suitabilitySample: System suitability solution Suitability requirements» Prepare Yellow Ointment as follows:Resolution: NLT 2.0 between olanzapine related com-pound A and olanzapineYellow Wax ....................50 g Tailing factor: 0.8–1.5 for the olanzapine peak Relative standard deviation: NMT 1.0% for the Petrolatum .....................950 g olanzapine peak to make .....................1000 gAnalysisSamples: Standard solution and Sample solutionMelt the Yellow Wax in a suitable dish on a Calculate the percentage of olanzapine (C 17H 20N 4S) in the steam bath, add the Petrolatum, warm until liq-portion of Olanzapine taken:uefied, then discontinue the heating, and stir the Result = (r U /r S ) × (C S /C U ) × 100mixture until it begins to congeal.r U = peak response from the Sample solution Packaging and storage—Preserve in well-closed containers.r S = peak response from the Standard solution C S= concentration of USP Olanzapine RS in theStandard solution (mg/mL)C U = concentration of olanzapine in the Samplesolution (mg/mL)OlanzapineAcceptance criteria: 98.0%–102.0% on the anhydrous,solvent-free basisIMPURITIES•R ESIDUE ON I GNITION 〈281〉: NMT 0.1%•H EAVY M ETALS , Method II 〈231〉: NMT 10 ppm •O RGANIC I MPURITIESBuffer: Dissolve 13g of sodium dodecyl sulfate in 1500 mLof water. Add 5 mL of phosphoric acid, and then adjust with a sodium hydroxide solution to a pH of 2.5.Solution A: Acetonitrile and Buffer (48:52)C 17H 20N 4S 312.43Solution B: Acetonitrile and Buffer (70:30)10H -Thieno[2,3-b ][1,5]benzodiazepine, 2-methyl-4-(4-methyl-1-Mobile phase: See Table 1.piperazinyl)-;2-Methyl-4-(4-methyl-1-piperazinyl)-10H -thieno [2,3-b ][1,5]benzodiazepine [132539-06-1].Table 1Time Solution ASolution BDEFINITION(min)(%)(%)Olanzapine contains NLT 98.0% and NMT 102.0% ofC 17H 20N 4S, calculated on the anhydrous, solvent-free basis.010********IDENTIFICATION200100•A . I NFRARED A BSORPTION 〈197K 〉250100•B . The retention time of the major peak of the Sample solu-271000tion corresponds to that of the Standard solution , as obtained in the Assay .35100ASSAYEdetate disodium solution: 37 mg/L of edetate disodium in •P ROCEDUREBufferBuffer: Dissolve 6.9 g of monobasic sodium phosphate in 1Diluent: Acetonitrile and Edetate disodium solution (40:60)L water. Adjust with phosphoric acid to a pH of 2.5, and System suitability solution: 20 µg/mL of USP Olanzapine then dissolve 12g of sodium dodecyl sulfate in the resulting RS and 2 µg/mL each of USP Olanzapine Related Compound solution.A RS and USP Olanzapine Related CompoundB RS in Diluent Mobile phase: Acetonitrile and Buffer (47:53)Standard solution: 2 µg/mL of USP Olanzapine RS in System suitability solution: 0.1 mg/mL of USP Olanzapine DiluentRS and 0.01 mg/mL of USP Olanzapine Related Compound Sample solution: 0.4 mg/mL of Olanzapine in Diluent A RS in Mobile phaseChromatographic systemStandard solution: 0.1 mg/mL of USP Olanzapine RS in Mo-(See Chromatography 〈621〉, System Suitability .)bile phaseMode: LCSample solution: 0.1 mg/mL of Olanzapine in Mobile phase Detector: UV 220 nmChromatographic systemColumn: 4.6-mm × 25-cm; 5-µm packing L7(See Chromatography 〈621〉, System Suitability .)Temperature Column: 35°Sample: 5°Flow rate: 1.5 mL/min Injection size: 20 µL System suitabilitySample: System suitability solution[N OTE —Identify the peaks using the Relative Retention Time values given in Table 2.]USP 35Official Monographs / Olanzapine4103Suitability requirements IDENTIFICATIONResolution: NLT 3.0 between olanzapine related•The retention times of the major peaks in the Sample solution compound A and olanzapine correspond to those in the Standard solution, as obtained in Tailing factor: NMT 1.5 for the olanzapine peak the Assay.Relative standard deviation: NMT 2.0% from 4ASSAYreplicate injections for the olanzapine peak•P ROCEDUREAnalysisBuffer: 37 mg/L of disodium ethylenediaminetetraacetate in Samples:Standard solution and Sample solutionwater. Add 3.3 mL of phosphoric acid, and adjust with 50% Calculate the percentage of each impurity in the portion ofsodium hydroxide to a pH of 2.5. Dissolve 8.7 g of sodium Olanzapine taken:dodecyl sulfate in the resulting solution.Mobile phase: Acetonitrile and Buffer (1:1)Result = (r U/r S) × (C S/C U) × (1/F) × 100Standard solution: 0.12 mg/mL of USP Olanzapine RS and r U= peak response of each impurity from the Sample0.45 mg/mL of USP Fluoxetine Hydrochloride RS in Mobile solution phaser S= peak response of olanzapine from the Standard Sample solution: 0.06–0.18 mg/mL of olanzapine and 0.25-solution0.5 mg/mL of fluoxetine in Mobile phase from a countedC S= concentration of USP Olanzapine RS in the number of CapsulesStandard solution (mg/mL)Chromatographic systemC U= concentration of olanzapine in the Sample(See Chromatography 〈621〉, System Suitability.)solution (mg/mL)Mode: LCF= relative response factor for each impurity from Detector: UV 227 nmTable 2Column: 4.6-mm × 7.5-cm; 3.5-µm packing L7 Acceptance criteria: See Table 2.Column temperature: 40°Flow rate: 2 mL/minInjection size: 10 µLTable 2Run time: 2.5 times the retention time of olanzapine Relative Relative Acceptance System suitabilityRetention Response Criteria,Sample:Standard solutionName Time Factor NMT (%)[N OTE—The relative retention times for olanzapine and Olanzapine related fluoxetine are 1.0 and 1.5, respectively.]compound B a0.3 2.30.10Suitability requirementsResolution: NLT 2.0 between olanzapine and fluoxetine Olanzapine relatedRelative standard deviation: NMT 2.0% for the compound A b0.8 1.00.10olanzapine and fluoxetine peaksOlanzapine 1.0——AnalysisAny individual,Samples:Standard solution and Sample solution unspecified——Calculate the percentage of C17H20N4S in the portion of Cap-impurity0.10sules taken:Total impurities——0.4a2-Methyl-10H-thieno-[2,3-b][1,5] benzodiazepin-4[5H]-one.Result = (r U/r S) × (C S/C U) × 100b5-Methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile.r U= peak response of olanzapine from the Sample SPECIFIC TESTS solution•W ATER D ETERMINATION, Method I〈921〉: NMT 1.0%rS= peak response of olanzapine from the Standard [N OTE—A suitable solvent system for water determination solutionin ketones and aldehydes (e.g., Hydranal composite 5K-CS= concentration of USP Olanzapine RS in the working medium K or Aquastar composite 5K-solvent KC Standard solution (mg/mL)or equivalent) is recommended.]CU= nominal concentration of olanzapine in theSample solution (mg/mL)ADDITIONAL REQUIREMENTSCalculate the percentage of C17H18F3NO in the portion of •P ACKAGING AND S TORAGE: Preserve in well-closed containers,Capsules taken:and store at room temperature.•USP R EFERENCE S TANDARDS〈11〉Result = (rU/r S) × (C S/C U) × (M r1/M r2) × 100 USP Olanzapine RSUSP Olanzapine Related Compound A RS rU= peak response of fluoxetine from the Sample 5-Methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile.solutionC12H9N3O2S259.28rS= peak response of fluoxetine from the Standard USP Olanzapine Related Compound B RS solution2-Methyl-10H-thieno-[2,3-b][1,5] benzodiazepin-4[5H]-one.CS= concentration of USP Fluoxetine Hydrochloride C12H10N2OS230.29RS in the Standard solution (mg/mL)C U= nominal concentration of fluoxetine in theSample solution (mg/mL)M r1= molecular weight of fluoxetine, 309.33M r2= molecular weight of fluoxetine hydrochloride, Olanzapine and Fluoxetine Capsules345.79Acceptance criteria: 90.0%–110.0%DEFINITIONPERFORMANCE TESTSOlanzapine and Fluoxetine Capsules contain an amount of•D ISSOLUTION〈711〉olanzapine and fluoxetine hydrochloride equivalent to NLTMedium: 0.1 N hydrochloric acid; 900 mL, deaerated90.0% and NMT 110.0% each of the labeled amount of[N OTE—Helium sparging recommended.]olanzapine (C17H20N4S) and fluoxetine (C17H18F3NO).Apparatus 2: 50 rpm, with 3-prong sinkersTime: 30 min for both olanzapine and fluoxetineStandard solution: USP Olanzapine RS and USP FluoxetineHydrochloride RS in Medium to obtain a final concentration。

重组人生长激素USP35

重组人生长激素 C 990H 1528N 262O 300S 7 22,125 [12629-01-5]. 重组人生长激素是一种191个氨基酸残基组成的由人垂体产生具有促生长作用的蛋白质。

可通过基因重组技术生产其冻干粉和水溶剂。

其冻干粉制剂中含量应不少于910μg/mg 重组人生长激素。

其水溶剂每mg 总蛋白量中含重组人生长激素应不少于910μg 。

重组人生长激素中的宿主细胞DNA 和宿主细胞蛋白残留限度标准需经被验证的方法确认。

生产企业必须采用基于促生长且经主管部门认可批准的经验证的生物测定方法证明其生物效价，可包含其赋形剂。

[注：每mg 无水重组人生长激素相当于3.0 USP 单位] 包装和贮存—密封容器中-10-25℃储存。

标签—标签应注明重组DNA 起源。

USP 参照标准<11>— USP 内毒素RS; USP 重组人生长激素RS 鉴别— A ：取适量USP 重组人生长激素标准品，用稀释液配制成浓度为2.0mg/ml 的标准溶液。

其余参照色谱纯度检查项下进行，用色谱程序分析标准品溶液和供试溶液：供试溶液色谱图中重组人生长激素主峰保留时间应与标准溶液一致。

B ：肽图（参见生物制品检测方法<1047>）溶液A —制备三氟乙酸水溶液（1:1000，v/v ），过滤，脱气。

溶液B —量取100ml 水加到1000ml 容量瓶中，再加1ml 三氟乙酸，最后用乙腈溶液稀释至终体积，并混匀。

流动相—溶液A 和溶液B 的变量混合液为色谱系统流动相。

必要时可调整任一溶液。

（参见色谱系统适应性<621>） Tris 缓冲液—配制0.05Mtris(羟甲基)甲胺溶液，用盐酸调节pH 至7.5。

胰蛋白酶溶液—用Tris 缓冲液制备1mg/ml 胰蛋白酶溶液，混匀，如有必要，冷冻保存。

标准溶液—用Tris 缓冲液制备2.0mg/ml USP 重组人生长激素标准品，混匀。

硫酸软骨素USP质量标准翻译

硫酸软骨素钠质量标准(USP）硫酸软骨素钠是从牛、猪、鸟类等家畜软骨组织中提取制得的硫酸化链状黏多糖钠盐.主要为N-乙酰半乳糖胺（2—乙酰胺-2脱氧—β—D-吡喃半乳糖）和D—葡萄糖全算的共聚物的硫酸酯的钠盐，共聚物内己糖通过β-1，4及β-1,3糖苷键交替连接.在普通使用的黏多糖中，硫酸基主要位于分子中半乳糖的4位上，少量的硫酸基在6位上。

在普遍使用的黏多糖中软骨糖胺部分主要为4-位单硫酸盐，少量为6—位.按干燥品计算，含硫酸软骨素钠90.0％~105。

0％。

注意:硫酸软骨素钠具有很强的引湿性,应避免暴露于空气中,称量应迅速。

包装、贮存:保存于密封容器.【溶液澄清度和颜色】取本品2.5g至50ml容量瓶中。

溶于不含二氧化碳的纯水中，并稀释至刻度，摇匀后立即检查.置于1cm吸收池内,在420nm波长处检测吸光度，以不含二氧化碳的水作为对照：吸光度不得大于0。

35。

【鉴别】A。

本品的红外光吸收图谱应与硫酸软骨素钠对照品的图谱一致.B。

取本品0。

5g溶于10ml纯水中,显钠盐的鉴别反应.【比旋度】取本品，精密称定，用水溶解并定量稀释制成每1ml中约含30mg的溶液。

测定，比旋度应为-20°至—30°。

【微生物限度】细菌总数不能超过1000 CFU/g，霉菌和酵母菌总数不能超过1000 CFU/g，在相同条件下不得检出沙门氏菌和大肠杆菌。

【pH】取本品0。

1g溶于10ml纯水中溶解，pH值为5。

5～7。

5.【干燥失重】取本品，在105℃干燥4小时，减失重量不得过10.0%。

（注意：硫酸软骨素钠有很强的吸湿性，应避免暴露于空气中，称量应迅速。

)【炽灼残渣】以干燥品计算，遗留残渣应为20.0％~30。

0%.【氯化物】取本品0。

10g，与0.7ml 盐酸（浓度0。

020 mol/L）对照液比较,不得更深（0.5％）。

【硫酸盐】取本品200mg溶于40ml水中,加入10ml(30mg/ml）西吡氯胺溶液，混匀，过滤。

乌苯美司胶囊含量均匀度测定方法学验证

乌苯美司胶囊含量均匀度测定方法学验证作者：姚阳来源：《今日健康》2014年第03期【摘要】乌苯美司胶囊可增强免疫功能，用于抗癌化疗、放疗的辅助治疗，老年性免疫功能缺陷等。

该实验通过对苯美司胶囊2010年版中国药典二部的含量均匀度测定方法进行验证，结果表明该方法可以准确测定乌苯美司的含量均匀度，可用于产品的质量控制。

【关键词】乌苯美司胶囊含量均与度方法学验证【中图分类号】 R927.2 【文献标识码】 A 【文章编号】 1671-5160（2014）03-0200-021 概述本方法学验证研究所用样品信息：样品名称：乌苯美司胶囊，规格：30mg，批号：130101 130102 1301032 试验研究内容2.1 乌苯美司胶囊含量均匀度方法学验证2.1.1 方法选择参照乌苯美司胶囊含量测定项下检测方法拟定本方法，按照2010版《中国药典》附录中药品质量标准分析方法验证指导原则要求，对该方法进行了验证。

2.1.2 仪器及色谱条件选用HPLC法作为含量均匀度的测定方法。

仪器：Waters2695液相色谱仪，2487紫外检测器，色谱柱柱：Inertsil ODS-3 5μ 150×4.6 （mm），柱温：40℃，流动相：甲醇-0.6%磷酸二氢钠溶液（45：55），流速：1.0ml/min，检测波长：254nm，试剂：甲醇（色谱纯）、磷酸二氢钠（AR）、水（重蒸水）拟定方法：取本品1粒，置于研钵中研细，将细粉倾入25ml量瓶中，研钵用适量的0.1mol/L盐酸溶液分次洗净，洗液并入量瓶中，充分振摇使乌苯美司溶解，用流动相稀释至刻度，摇匀，滤过，作为供试品溶液。

按照上述仪器及色谱条件，精密量取20ul注入液相色谱仪，记录色谱图；另取105℃干燥至恒重的乌苯美司对照品，精密称定，同法配制成每1ml约含1.2mg乌苯美司的溶液，作为对照品溶液，同法测定，按外标法以峰面积计算，即得。

理论板数以乌苯美司峰计应不低于3500。

环孢素-USP35

USP 35Official Monographs / Cyclosporine2793 Dissolution 〈711〉—amino-6-octenoyl-L-α-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl) [59865-13-3].Medium: pH 6.8 Phosphate buffer (see Buffer Solutions underSolutions in the section Reagents, Indicators, and Solutions); 900» Cyclosporine contains not less than 98.5 per-mL.cent and not more than 101.5 per cent of Apparatus 1: 100 rpm.cyclosporine A (C62H111N11O12), calculated on the Time: 30 minutes.dried basis.Determine the amount of C3H6N2O2 dissolved by employingthe following method.Packaging and storage—Preserve in tight, light-resistant pH 6.8 Phosphate buffer, Mobile phase, and Chromatographic containers.system—Proceed as directed in the Assay.Standard solution—Quantitatively dissolve an accurately USP Reference standards 〈11〉—weighed quantity of USP Cycloserine RS in pH 6.8 Phosphate USP Cyclosporine RSbuffer to obtain a solution having a known concentration of USP Cyclosporine Resolution Mixture RSabout 0.25 mg per mL.This material is a 100:1 mixture of cyclosporine andcyclosporine U.Test solution—Use a filtered portion of the solution undertest.Identification—The chromatogram of the Assay preparationobtained as directed in the Assay exhibits a major peak for Procedure—Separately inject equal volumes (about 10 µL) ofcyclosporine, the retention time of which corresponds to that the Standard solution and the Test solution into the chromato-exhibited in the chromatogram of the Standard preparation, as graph, record the chromatograms, and measure the peak re-obtained in the Assay.sponses for cycloserine. Calculate the quantity, in mg, of cyc-loserine (C3H6N2O2) dissolved by the formula:Loss on drying 〈731〉—Dry about 100 mg, accuratelyweighed, in a capillar y-stoppered bottle in vacuum at a pressure 900C(r U/r S)not exceeding 5 mm of mer cury at 60° for 3 hours: it loses notmore than 2.0% of its weight.in which C is the concentration, in mg per mL, of USP Cycloser-Heavy metals, Method II 〈231〉: 0.002%.ine RS in the Standard solution; and r U and r S are the peak re-Related compounds—Using the chromatograms obtained sponses for cycloserine obtained from the Test solution and thefrom Standard preparation 2 and the Assay preparation in the Standard solution, respectively.Assay, calculate the per centage of each impurity by the formula: Tolerances—Not less than 80% (Q) of the labeled amount ofC3H6N2O2 is dissolved in 30 minutes.2000(C/W)(ri/r S2)Uniformity of dosage units 〈905〉: meet the requirements.in which C is the concentration, in mg per mL, of USPLoss on drying 〈731〉—Dry about 100 mg of the contents ofCyclosporine RS in Standard preparation 2; W is the weight, in Capsules in a capillar y-stoppered bottle in vacuum at 60° for 3mg, of Cyclosporine taken to prepare the Assay preparation; r i is hours: it loses not more than 1.0% of its weight.the response of an individual impurity obser ved in the chromat-Assay—ogram of the Assay preparation; and r S2 is the response of the pH 6.8 Phosphate buffer, Mobile phase, Standard preparation,main cyclosporine peak in the chromatogram obtained from and Chromatographic system—Proceed as directed in the Assay Standard preparation 2: not more than 0.7% of any individual under Cycloserine.impurity is found, and the sum of all such impurities is not Assay preparation—Remove, as completely as possible, the more than 1.5%, any impurities corresponding to less than contents of not fewer than 20 Capsules. T ransfer an accurately0.05% being disregarded.weighed portion of the powder, equivalent to about 100 mg of Assay—cycloserine, to a 250-mL volumetric flask, dilute with pH 6.8Mobile phase—Prepare a mixture of water, acetonitrile, tert-Phosphate buffer to volume, mix, and filter.butyl methyl ether, and phosphoric acid (520:430:50:1). Make Procedure—Proceed as directed in the Assay under Cycloser-adjustments if necessar y (see System Suitability under Chroma-ine. Calculate the quantity, in mg, of cycloserine (C3H6N2O2) in tography 〈621〉).the portion of Capsules taken by the formula:Diluent—Prepare a mixture of acetonitrile and water (1:1).250C(r U/r S)Standard preparation 1—Dissolve an accurately weighedquantity of USP Cyclosporine RS in Diluent to obtain a solution in which the terms are as defined therein.having a known concentration of about 1.25 mg per mL.Standard preparation 2—Transfer 2.0 mL of Standard prepara-tion 1 to a 250-mL volumetric flask, dilute with Diluent to vol-ume, and mix. This solution contains about 0.01 mg of USPCyclosporine RS per mL.CyclosporineAssay preparation—Dissolve about 25 mg of Cyclosporine,accurately weighed, in Diluent, dilute with Diluent to 20.0 mL,and mix.Resolution solution—Prepare a solution of USP CyclosporineResolution Mixture RS in Diluent having a concentration ofabout 1.25 mg per mL.Chromatographic system (see Chromatography 〈621〉)—Theliquid chromatograph is equipped with a 210-nm detector, a0.25-mm × 1-m stainless steel tube connected to a 4-mm × 25-cm column that contains 3- to 5-µm packing L1. The tube and C62H111N11O121202.61column are maintained at 80°. The flow rate is about 1.2 mL Cyclo[[(E)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)-6-per minute. Chromatograph the Resolution solution, and record octenoyl]-L-2-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-the responses as directed for Procedure: the cyclosporine U peak L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-and the main cyclosporine peak are resolved from each other. methyl-L-leucyl-N-methyl-L-valyl].Chromatograph Standard preparation 1, and record the re-[R-[R*,R*-(E)]]-Cyclic(L-alanyl-D-alanyl-N-methyl-L-leucyl-N-sponses as directed for Procedure: the relative standard deviation methyl-L-leucyl-N-methyl-L-valyl-3-hydroxy-N,4-dimethyl-L-2-for replicate injections is not more than 1.0%. Chromatograph2794Cyclosporine / Official Monographs USP 35Standard preparation 2, and record the responses as directed for Test solution—Filter a portion of the solution under test. Procedure: the relative standard deviation for replicate injections Transfer 5.0 mL of the filtrate to a 10-mL volumetric flask, dilute is not more than 10%.with acetonitrile to volume, and mix.Procedure—[NOTE—Use peak areas where peak responses are Chromatographic system (see Chromatography 〈621〉)—The indicated.] Separately inject equal volumes (about 20 µL) of liquid chromatograph is equipped with a 210-nm detector and Standard preparation 1, Standard preparation 2, and the Assay a 4.6-mm × 25-cm column that contains packing L1 and is preparation into the chromatograph, record the chromato-maintained at a constant temperature of about 80°. The flow grams, and measure the peak responses. Calculate the per cent-rate is about 2 mL per minute. Chromatograph the Standard age of cyclosporine A (C62H111N11O12) in the Cyclosporine taken solution, and record the peak areas as directed for Procedure:by the formula:the column efficiency is not less than 700 theoretical plates;and the relative standard deviation for replicate injections is not (CP/10U)(r U/r S)more than 2.0%.Procedure—Separately inject equal volumes (about 10 µL) of in which C is the concentration, in mg per mL, of USP the solution estimated to contain 0.1 mg of cyclosporine per Cyclosporine RS in Standard preparation 1; P is the specified mL, or 40 µL of the solution estimated to contain 0.025 mg of purity, in µg per mg, of USP Cyclosporine RS; U is the concen-cyclosporine per mL) of the Standard solution and the Test solu-tration, in mg per mL, of specimen in the Assay preparation;tion into the chromatograph, record the chromatograms, and and r U and r S are the main cyclosporine peak responses ob-measure the areas for the major peaks. Calculate the quantity, tained from the Assay preparation and Standard preparation 1,in mg, of C62H111N11O12 dissolved by the formula: respectively.2000C(r U/r S)in which C is the concentration, in mg per mL, of USPCyclosporine RS in the Standard solution; and r U and r S are the Cyclosporine Capsules cyclosporine peak areas obtained from the Test solution and theStandard solution, respectively.» Cyclosporine Capsules contain not less than Tolerances—Not less than 80% (Q) of the labeled amount of 90.0 percent and not more than 110.0 per cent C62H111N11O12 is dissolved in 90 minutes.of the labeled amount of cyclosporine Uniformity of dosage units 〈905〉: meet the requirements. (C62H111N11O12).Water, Method I 〈921〉—For Capsules that contain powder, notmore than 3.5% is found, using finely ground Capsule Packaging and storage—Preserve in tight containers, and contents.store at controlled room temperature.Assay—Identification—The retention time of the major peak in theWHERE CAPSULES CONTAIN LIQUID—chromatogram of the Assay preparation corresponds to that inMobile phase and Chromatographic system—Proceed as di-the chromatogram of the Standard preparation, as obtained inrected in the Assay under Cyclosporine Injection.the Assay.Standard preparation—Dissolve an accurately weighed quan-Dissolution 〈711〉—tity of USP Cyclosporine RS in dehydrated alcohol to obtain a WHERE CAPSULES CONTAIN LIQUID—solution having a known concentration of about 1 mg per mL.Medium: water; 500 e this solution promptly after preparation.Apparatus 2: 50 rpm.Assay preparation—Using a sharp blade, carefully cut open Time: 15 minutes.not fewer than 20 Capsules, and with the aid of dehydratedalcohol transfer the contents of the Capsules to a suitable volu-Procedure—Place 1 Capsule in each vessel, and allow themetric flask. Wash the blade with dehydrated alcohol, and Capsule to sink to the bottom of the vessel before starting rota-transfer the washings to the volumetric flask. Dilute the con-tion of the blade. Obser ve the Capsules, and record the timetents of the volumetric flask with dehydrated alcohol to volume, taken for each Capsule shell to rupture.and mix. Quantitatively dilute an accurately measured volume Tolerances—The requirements are met if all of the Capsulesof this solution with dehydrated alcohol to obtain a solution tested rupture in not more than 15 minutes. If 1 or 2 of thehaving a concentration of about 1 mg of cyclosporine per mL. Capsules rupture in more than 15 but not more than 30 min-Procedure—Separately inject equal volumes (about 20 µL) of utes, repeat the test on 12 additional Capsules. Not more thanthe Standard preparation and the Assay preparation into the2 of the total of 18 Capsules tested rupture in more than 15chromatograph, record the chromatograms, and measure the but not more than 30 minutes.areas for the major peaks. Calculate the quantity, in mg, of WHERE CAPSULES CONTAIN POWDER—cyclosporine (C62H111N11O12) in each Capsule taken by the Medium: 0.1 N hydrochloric acid containing 0.5% of so-formula:dium lauryl sulfate; 1000 mL.Apparatus 1: 150 rpm.(L/D)(CP/1000)(r U/r S)Time: 90 minutes.in which L is the labeled quantity, in mg, of cyclosporine in Determine the amount of C62H111N11O12 dissolved by employ-each Capsule taken; D is the concentration, in mg per mL, of ing the following method.the Assay preparation, based on the labeled quantity of Mobile phase—Prepare a filtered and degassed mixture of ac-cyclosporine in the Capsules taken and the extent of dilution; C etonitrile, water, methanol, and phosphoric acidis the concentration, in mg per mL, of USP Cyclosporine RS in (900:450:50:0.5). Make adjustments if necessar y (see Systemthe Standard preparation; P is the purity, in µg per mg, of USP Suitability under Chromatography 〈621〉).Cyclosporine RS; and r U and r S are the peak areas obtained from Standard solution—Quantitatively dissolve an accurately the Assay preparation and the Standard preparation, respectively. weighed quantity of USP Cyclosporine RS in Dissolution MediumWHERE CAPSULES CONTAIN POWDER—to obtain a solution having a known concentration of aboutMobile phase—Prepare a filtered and degassed mixture of ac-0.001L mg per mL, L being the labeled quantity, in mg, ofetonitrile, water, methanol, and phosphoric acidcyclosporine in each Capsule. T ransfer 25.0 mL of this solution(605:400:50:0.5). Make adjustments if necessar y (see Systemto a 50-mL volumetric flask, dilute with acetonitrile to volume,Suitability under Chromatography 〈621〉).and mix. This solution contains about 0.0005L mg of USPCyclosporine RS per mL.。

口服缓控释制剂的相关要求与质量评价(一)

口服缓控释制剂的相关要求与质量评价（一）
一、USP对口服缓控释制剂的相关要求
（一）药物释放要求
USP规定的缓控释制剂的释放试验方法是以药物自其剂量单元的溶m为基础的，对各种实验装置和操作方法的详尽描述参见USP第724章。

每个药物制剂品种项卜×寸药物的溶出度标准作了明确的规定，如对于阿司匹林缓释片的释放速率的要求见表1 3。

（二）单位剂量均匀性
调节释放型药物制剂必须符合USP中对其单位剂量均匀性的标准，评价方法有两种，即考察重量差异或含量均匀度，详见USP第905章。

（三）体内外相关性
体内外相关性(IVIVCs，In Vitro/ln Vivo Correlations或IVIVR，
In Vitro/ln Vivo Relationships)对于口服缓控释制剂的开发非常重要，对体内外相关性的评价在产品开发、临床评价、向FDA递交上市申请、批准后按建议更改处方或制备方法的过程中都起着关键性的作用。

1997年，FDA出版了关于缓控释制剂的指导性文件《口服缓释剂型体内外相关性的发展、评价及其应用》。

该文件提供了多种关于体内外相关性的研究方法：①开发体内外相关研究模型并评价其预测性。

②利用体内外相关性建立释放度标准。

③将体内外相关性作为体内生物等效性研究的重要依据。

剂量均匀性-USP35

（二）可接受值的计算
按照含量均匀度项下方法计算，但单个样品的含量值用单个样品的估计含量值代替。
X1，X2，…，Xn =单个被测样品的标示量估计值； xi = w i × A ÷ w W1 W W , 2，…， n =单个被测样品的重量值 A=采用合适检验方法得到的样品标示量
W =单个样品重量的平均值三、准则除有特殊规定外，应执行以下准则。固体、半固体和液体制剂如第一次测得的 10 个样品的剂量均匀性的接受值（AV）不大于 L1%，则判定该样品的剂量均匀项合格；如接受值（AV）大于 L1%，继续检验另 20 个样品，计算接受值（AV），如 30 个样品最终的接受值（AV）不大于 L1%，且任一样品标示量不少于【1-0.01*L2】*M，不大于 1+0.01*L2】*M（如无特殊规定， L1=15.0，L2=25.0），则该样品的剂量均匀项也判定为合格。
菌固体制剂）
单剂量包装、含有或不含有活性或非活性添加成分，在最终包装容器中采用溶液 W3
冻干工艺制备，且在标签中标明该制备方法的固体制剂（包括无菌固体制剂）
硬胶囊、素片或薄膜衣片，含 25mg 或以上的药物主成分，占制剂重量的比值为 W4 25%或以上。如为硬胶囊，胶囊的含量（除次要药物组分的均匀度外）用满足含
1、素片、薄膜包衣片
2、硬胶囊：
取胶囊 10 颗，分别精密称定，小心做好每颗胶囊的标记。用适宜的方法移除每颗胶囊的内容物。分别精密称定每颗胶囊的外壳。计算每颗胶囊内容物的重量。计算方法为：标示量*（每颗胶囊总量-每颗胶囊壳重量）。计算 AC（可接受值）。
3、软胶囊
4、除片剂、胶囊外的固体制剂
5、液体制剂
量均匀度项下要求的方式表示。
其他不满足上表规定的，均采用含量均匀度项目来考察剂量均匀性。