口服固体制剂通则比较.ppt

nImpurity 杂质Content uniformity 含量均匀度Uniformity of Dosage Unite 单位制剂均匀度郭建芳（Janie ）© 2008-12-29； in SLP Limited Co.，FOR PHARMACOPIEA TRAININGIMPURITIES 杂质郭建芳（Janie ） December 2008CONTENT 内容ANALISIS METHODREFERENCERESIDUAL SOLVENTDEFINITION LIMITEDReference有关章节 中国药典(Chp)附录ⅩⅨ F 药品杂质分析指导原则 附录Ⅷ 残留溶剂测定法欧洲药典(EP60) 5.4 Residual Solvents 5.10 Control of Impurities in Substances for Pharmaceutical Use 2034 Substances for Pharmaceutical Use 美国药典(USP31)466 Ordinary Impurities 467 Organic Volatile Impurities 1086 Impurities in Official Articles REFERENCEDEFINITION of IMPURITY 杂质的定义ChP.杂质：影响药品纯度的物质。

在药品质量标准中的杂质：在按照国家有关药品监督管理部门 依法审查批准的规定工艺和规定原辅料生产的药品中，由其生 产工艺或原辅料带入的杂质，或经稳定性试验确证的在贮存过 程中产生的降解产物 不包括：1.变更生产工艺or原辅料产生的新杂质2.渗入或污染的外来物质 Ordinary impurities : those species in drug substances and/or drug products that have no significant, undesirable biological activity in the amounts present.〈466〉 一般杂质：在现剂量药物（或其制剂）中的无明显不良生物 学活性的物质USPEP 杂质：药用物质里面任何非药物的化学实体DEFINITION of Related Substances 有关物质的定义ChP.有关物质：包括化学反应的前体、中间体、副产 物和降解产物等Related Substances— Related substances are structurally related to a drug substance. 有关物质—有关物质与药物有结构相关性。

These substances may be (a) identified or unidentified impurities arising from synthesis manufacturing process such as intermediates or by-products and do not increase on storage or identified or unidentified degradation products that result from drug substance or drug product manufacturing processes or arise during storage of a material. USPEP有关物质：个论中用于有机杂质一般检验的标题See 〈5.10〉Other Definitions其他定义（已知杂质、 特定杂质）Identified Impurities and Identified Degradation Products— Impurities or degradation products for which structural characterizations have been achieved. Specified Impurities and Specified Degradation Products— Previously referred to as Signal Impurities, specified impurities or specified degradation products are impurities or degradation products that are individually listed and limited with specific acceptance criteria in individual monographs as applicable. Specified impurities or specified degradation products can be identified or unidentified. 〈1086〉USPEPOther Definitions其他定义（共存物质）Concomitant components defined as species characteristic of many drug substances that are not considered to be impurities in the Pharmacopeial sense. Examples of concomitant components are geometric and optical isomers (or racemates) and antibiotics that are mixtures. Any component that can be considered a toxic impurity because of significant undesirable biological effect is not considered to be a concomitant component. 共存物质：很多药物的特殊种类，在药典意义上不认为是杂质。

共 存物质如几何异构体，旋光异构体（或外消旋物）或者是多组分抗生 素等有不良生物学活性的毒性物质除外） 无定义共存异构体和抗生素多组分一般不作为杂质检查项目， 必要时，在质量标准中规定其比例，共存物质是毒性杂质时，不再认 为是共存物质）无相关定义USPEPChP.Other Definitions其他定义Other Impurities其他杂质— Official substances may be obtained from more than one process, and thus may contain impurities not considered during preparation of monograph assays or tests. 〈Tests and Assays 〉USPForeign Substances 外来物质(Extraneous Contaminants)— Foreign substances (extraneous contaminants), which are introduced by contamination or adulteration, are not consequences of the synthesis or preparation of compendial articles and thus cannot be anticipated when monograph tests and assays are selected. Inorganic Impurities无机杂质— Inorganic impurities can result from the manufacturing process (e.g., residual metals, inorganic salts, filter aids, etc.). Process Contaminants过程污染物— Process contaminants are identified or unidentified substances (excluding related substances and water), including reagents, catalysts, other inorganic impurities (e.g., heavy metals, chloride, or sulfate); and may also include foreign substances (extraneous contaminants). These contaminants may be introduced during manufacturing or handling procedures. Toxic Impurities毒性杂质— Toxic impurities have significant undesirable biological activity, even as minor components, and require individual identification and quantification by specific tests. Other Definitions其他定义EP其他可检测杂质 See 〈5.10〉潜在杂质 See 〈5.10〉ANALISIS METHOD药典中杂质检测方法ü 要求： 专属、灵敏ü 尽量使用现代分离分析手段，使主成分与杂 质和降解物质均能分开ü 有机杂质：化学法、光谱法、色谱法。

ü 其中常用的有HPLC、TLC、GC、CE（毛 细管电泳） ü 其中USP〈466〉的典型方法：TLC法ANALISIS METHOD药典中杂质检测方法无机杂质：ü 重金属的检查：重金属限度检查法（如 砷盐检查法）、原子分光光度法、比色 法等ü 不挥发性无机杂质：炙灼残渣法等ü 其他方法：如离子色谱法、电感耦合等 发射光谱-质谱（ICP-MS）•Limited 杂质限度A A中国药典B BUSP药典C CEP药典要求： 质量标准中规定单个杂质的限量和总杂质的限量 限度制定考虑因素：杂质及含一定限量杂质的药品 的毒理学研究结果；给药途径；每日剂量；给药人群 ；杂质药理学可能的研究结果；原料药的来源；治疗 周期；在保证安全有效期的前提下，药品生产企业对 生产高质量药品所需成本和消费者对药品价格的承受 力 Reporting and Specifications— The value of 2.0%, unless otherwise specified in the individual monograph, was selected as the general limit for the total amount of ordinary impurities in monographs where documentation did not support adoption of other values. See2034-1EP2034 limits药典中的杂质A A中国药典B BUSP药典C CEP药典杂质 残留溶剂Ordinary impurity Residual solventsImpurities Residual solvents残留溶剂定义A A中国药典B BUSP药典C CEP药典在原料药或辅料的生产中，以及在制剂 制备过程中使用的，但在工艺过程中未 能完全去除的有机溶剂。

For pharmacopeial。