232 中英文对照

<232>ELEMENTAL IMPURITIES—LIMITS元素杂质—限度INTRODUCTION介绍This general chapter specifies limits for the amounts of elemental impurities in drug products. Elemental impurities include catalysts and environmental contaminants that may be present in drug substances,excipients,or drug products.These impurities may occur naturally,be added intentionally,or be introduced inadvertently(e.g.,by interactions with processing equipment). When elemental impurities are known to be present,have been added,or have the potential for introduction,assurance of compliance to the specified levels is required.A risk-based control strategy may be appropriate when analysts determine how to assure compliance with this standard.Due to the ubiquitous nature of As,Cd,Pb,and Hg,they(at the minimum)must be considered in the risk-based control strategy.Regardless of the approach used,compliance with the limits specified is required for all drug products.本章说明了药品中元素杂质的数量限度。

元素杂质包括可能会存在于原料药、辅料或制剂中的催化剂和环境污染物。

这些杂质可能会自然生成的、有意加入的或不可逆引入（例如与生产设备的相互反应）的。

如果已知元素杂质存在、被加入或有引入的可能性，则必须保证其符合指定限度。

分析人员在决定如何保证符合本标准时，可以适当采用基于风险的控制策略。

由于砷、镉、铅和汞在自然中普遍存在，在采用基于风险的控制策略时必须包括对这四种元素的考虑。

不论采用何种方式，所有药品均需符合指定的限度。

The limits presented in this chapter do not apply to excipients and drug substances,except where specified in this chapter or in the individual monographs.However,elemental impurity levels present in drug substances and excipients must be known and reported.在本章中给出的限度不适用于辅料和原料药，除非在本章或各论中有说明。

但是，原料药和辅料中的元素杂质水平必须知道并报告。

The limits indicated in this chapter are not required for articles intended only for veterinary use and conventional vaccines.Dietary supplements and their ingredients are addressed in Elemental Contaminants in Dietary Supplements2232.1本章中指出的限度不适用于仅供兽用品种和传统疫苗。

膳食补充剂及其成分在《膳食补充剂元素污染物2232》中已有说明。

SPECIATION杂质形态The determination of the oxidation state,organic complex,or combination is termed speciation. Each of the elemental impurities has the potential to be present in differing oxidation or complexation states.However,arsenic and mercury are of particular concern because of the differing toxicities of their inorganic and complexed organic forms.不同形式如氧化态、有机复合物或复合状态称为杂质形态。

每一种元素杂质都可能会以不同的氧化或复合状态存在。

但因为砷和汞的有机形态和复合无机形态的毒性有差异，因而其受到特别关The arsenic limits are based on the inorganic(most toxic)form.Arsenic can be measured using a total arsenic procedure under the assumption that all arsenic contained in the material under test is in the inorganic form.Where the limit is exceeded using a total arsenic procedure, it may be possible to show via a procedure that quantifies the different forms that the inorganic form meets the specification.砷限度是基于无机（大多是有毒的）形式。

假定物料中含有的砷均为无机形式，则可以采用总砷测试方式进行检测，如果采用总砷量检测结果显示超出限度，也可以对不同砷的存在方式进行定量检测，来证明有机砷符合限度规定。

The mercury limits are based upon the inorganic(2+)oxidation state.The methyl mercury form (most toxic)is rarely an issue for pharmaceuticals.Thus,the limit was established assuming the most common(mercuric)inorganic form.Limits for articles that have the potential to contain methyl mercury(e.g.,materials derived from fish)are to be provided in the monograph.汞限度是基于无机二价氧化态。

甲基汞形式（毒性最强）对于药物来说影响最大。

因而，对汞的限度设定是假定其为最常见（汞盐）无机形式。

对于可能含有甲基汞（例如鱼制品）的产品，其限度在各论中均有包括。

ROUTES OF EXPOSURE暴露途径The toxicity of an elemental impurity is related to its extent of exposure(bioavailability).The extent of exposure has been determined for each of the elemental impurities of interest for three routes of administration:oral,parenteral,and inhalational.These limits are based on chronic exposure.The other two routes of administration,mucosal and topical,are considered to be the same as oral for the purpose of this standard,and the PDEs described in Table1 would apply to these products.[NOTE—The routes of administration of drug products are defined in general chapter Pharmaceutical Dosage Forms1151.]每种元素杂质的毒性与其暴露程度（生物利用度）有关。

各元素杂质的在三种给药途径下的暴露程度已经过测定：口服、注射和吸入。

这些限度是基于长期暴露的数据制订的。

其它两种给药途径：粘膜和局部给药，是作为与口服一样考虑的，因此在相同PDE下，表1中的限度同样适用于该类产品。

【注---制剂给药途径在通论中有定义《药物制剂形式1151》】DRUG PRODUCTS制剂The limits described in the second through fourth columns of Table1are the base daily dose PDEs of the elemental impurities of interest for a drug product taken by the patient according to indicated routes of administration.Parenterals with an intended maximum dose of greater than10mL and not more than100mL must use the Summation Option described below.在表1的第2至第4列所指限度是基于日剂量计算的各元素杂质的由病人在指定摄入途径下的日最大允许暴露量。

注射剂如果最大剂量超过10ml，但不超过100ml，必须使用下述的《加和方式》Large Volume Parenterals大容量注射液When the daily dose of an injection is greater than100mL(large volume parenteral(LVP)),the amount of elemental impurities present in the drug product must be controlled through the individual components used to produce the product.The amounts of elemental impurities present in each component used in an LVP are less than the values included in the fifth column of Table1.如果注射剂日剂量超过100ml（大容量注射剂LVP），药品中的元素杂质必须通过用于生产的单个原辅料来进行控制。