USP 《233》ELEMENTAL IMPURITIES—PROCEDURES 中英对照

?233? ELEMENTAL IMPURITIES—PROCEDURES

元素杂质-程序

INTRODUCTION 介绍

This chapter describes two analytical procedures (Procedures 1 and 2) for the evaluation of the levels of the elemental impurities. The chapter also describes criteria for acceptable alternative procedures. By means of validation studies, analysts will confirm that the analytical procedures described herein are suitable for use on specified material.

本章描述了评价元素杂质水平的两种分析方法(程序1和程序2)。本章还描述了可接受的替代程序的标准。通过验证研究，分析人员将确认本文描述的分析方法适用于特定的物料。 Use of Alternative Procedures 使用替代程序

The chapter also describes criteria for acceptable alternative procedures. Alternative procedures that meet the validation requirements herein may be used in accordance with General Notices, 6.30 Alternative and Harmonized Methods and Procedures. Information on the Requirements for Alternate Procedure Validation is provided later in this chapter.

本章还描述了可接受的替代程序。可根据通则6.30替代和协调的方法和程序使用满足本文验证要求的替代方法和程序。关于备用工艺验证要求的信息将在本章后面提供。

Speciation 形态

The determination of the oxidation state, organic complex, or combination is termed speciation. Analytical procedures for speciation are not included in this chapter, but examples may be found elsewhere in USP–NF and in the literature.

氧化态、有机络合物或组合的测定称为形态。本章不包括物种形成的分析方法，但可以在USP-NF中其他地方和文献中找到例子。

PROCEDURES 程序

?Compendial Procedures 1 and 2 程序1和2

System standardization and suitability evaluation using applicable reference materials should be performed on the day of analysis.

使用标准物质进行系统标化和适用性评估应在分析当天进行。

Procedure and detection technique: Procedure 1 can be used for elemental impurities generally amenable to detection by inductively coupled plasma–atomic (optical) emission spectroscopy (ICP–AES or ICP–OES). Procedure 2 can be used for elemental impurities generally amenable to detection by ICP–MS. Before initial use, the analyst should verify that the procedure is

appropriate for the instrument and sample used (procedural verification) by meeting the alternative procedure validation requirements below. 程序和检测技术：程序1可用于一般适用于电感耦合等离子体原子(光学)发射光谱(ICP-AES或ICP-OES)检测的元素杂质。程序2可用于一般适用于ICP-MS检测的元素杂质。在首次使用前，检验员应通过满足以下替代程序验证（程序确认）要求来验证程序适用于所使用的仪器和样品。

Sample preparation: Forms of sample preparation include Neat, Direct aqueous solution, Direct organic solution, and Indirect solution. The selection of the appropriate sample preparation depends on the material under test and is the responsibility of the analyst. When a sample preparation is not indicated in the monograph, an analyst may use any of the following

appropriately validated preparation procedures. In cases where spiking of a material under test is necessary to provide an acceptable signal intensity, the blank should be spiked with the same

Target elements, and where possible, using the same spiking solution. Standard solutions may contain multiple Target elements. [Note—All liquid samples should be weighed.]

样品制备：样品制备形式包括净溶液、直接水溶液、直接有机溶液和间接溶液。选择合适的样品制剂取决于被测材料，这是分析员的责任。当各论中未指明样品制备时，检验员可使用下列任何经适当验证的制备程序。如果为了提供可接受的信号强度，有必要对被测材料进行加钉，则空白材料应使用相同的目标元素，并在可能的情况下，使用相同的加钉溶液。标准溶液可能包含多个目标素。【注:所有液体样品均需称重】

Neat: Used for liquids or alternative procedures that allow the examination of unsolvated samples. 净溶液：用于液体或允许检查未溶解样品的替代程序

Direct aqueous solution: Used when the sample is soluble in an aqueous solvent. 直接水溶液：当样品可溶于水溶剂时使用。

Direct organic solution: Used where the sample is soluble in an organic solvent. 直接有机溶液：适用于样品可以溶解在有机溶剂的情况。

Indirect solution: Used when a material is not directly soluble in aqueous or organic solvents. Total metal extraction is the preferred sample preparation approach to obtain an Indirect solution. Digest the sample using the Closed vessel digestion procedure provided below or one similar to it. The sample preparation scheme should yield sufficient sample to allow quantification of each element at the limit specified in the corresponding monograph or chapter. 间接溶液：当一种材料不能直接溶于水或有机溶剂时使用。全金属萃取是获得间接溶液的首选样品制备方法。使用下面提供的封闭容器消化程序或类似的程序消化样品。样品制备方案应提供足够的样品，以允许在相应的专论或章节规定的限度内定量每个元素。

Closed vessel digestion: This sample preparation procedure is designed for samples that must be digested in a Concentrated acid using a closed vessel digestion apparatus. Closed vessel

digestion minimizes the loss of volatile impurities. The choice of a Concentrated acid depends on the sample matrix. The use of any of the Concentrated acids may be appropriate, but each introduces inherent safety risks. Therefore, appropriate safety precautions should be used at all times. [Note—Weights and volumes provided may be adjusted to meet the requirements of the digestion apparatus used.] 封闭的消化容器：此样品制备程序是为必须在浓酸中使用密闭容器消化装置消化的样品设计的。密闭容器消化将挥发性杂质的损失降至最低。浓酸的选择取决于样品基质。任何一种浓酸的使用都可能是合适的，但每一种都会带来固有的安全风险。因此，任何时候都应该采取适当的安全措施。【注:所提供的重量和体积可调整以满足所使用的消化设备的要求】 An example procedure that has been shown to have broad applicability is the following.

Dehydrate and predigest 0.5 g of primary sample in 5 mL of freshly prepared Concentrated acid. Allow to sit loosely covered for 30 min in a fume hood. Add an additional 10 mL of Concentrated acid, and digest, using a closed vessel technique, until digestion or extraction is complete. Repeat, if necessary, by adding an additional 5 mL of Concentrated acid. [Note—Where closed vessel digestion is necessary, follow the manufacturer’s recommended procedures to ensure safe use.] 下面是一个已被证明具有广泛适用性的示例过程。将0.5 g样品脱水并放入5ml新鲜配制的浓酸中预消化。在通风柜中放置30分钟。再加入10毫升浓酸，用密闭容器技术消化，直到消化或提取完成。如有必要，再加5ml浓酸。【注：如果需要密闭容器消化，请遵循制造商推荐的程序，以确保安全使用】

Alternatively, leachate extraction may be appropriate with justification following scientifically validated metal disposition studies, which may include animal studies, speciation, or other means of studying disposition of the specific metal in the drug product.

另外，在经过科学验证的金属处理研究之后，浸出液提取可能是适当的，这些研究可能包括动物研究、物种形成或研究药品中特定金属处理的其他方法。

Reagents: All reagents used for the preparation of sample and standard solutions should be free of elemental impurities, in accordance with Plasma Spectrochemistry ?730?.

试剂：所有用于制备样品和标准溶液的试剂应不含元素杂质，符合等离子体光谱化学< 730 >。

?Procedure 1: ICP–OES 程序1：ICP-MS

Standardization solution 1:1.5J of the Target element(s) in a Matched matrix 标准溶液1：匹配基质中目标元素的1.5J

Standardization solution 2:0.5J of the Target element(s) in a Matched matrix 标准溶液2：匹配基质中目标元素的0.5J

Sample stock solution: Proceed as directed in Sample preparation above. Allow the sample to cool, if necessary. For mercury determination, add an appropriate stabilizer.

样品储备溶液：按照上面样品制备的要求进行。如有必要，允许样品冷却。对于汞的测定，添加适当的稳定剂。

Sample solution: Dilute the Sample stock solution with an appropriate solvent to obtain a final concentration of the Target elements at NMT 1.5J.

样品溶液：用适当的溶剂稀释样品储备溶液，以获得目标元素的最终浓度为不大于1.5J。 Blank: Matched matrix 空白：匹配基质

Elemental spectrometric system (See Plasma Spectrochemistry ?730?.) 元素光谱系统（见《730》等离子体光谱化学） Mode: ICP 模式：ICP

Detector: Optical detection system 检测器：光学检测系统 Rinse: Diluent used 冲洗：使用稀释剂

Standardization: Standardization solution 1, Standardization solution 2, and Blank 校准：标化溶液1，标化溶液2，和空白溶液 System suitability 系统适用性

Sample: Standardization solution 1 样品：标化溶液1

Suitability requirements 系统适用性要求

Drift: Compare results obtained from Standardization solution 1 before and after the analysis of the Sample solution.

漂移：比较标准化溶液1分析样品溶液前后的结果。

Suitability criteria: NMT 20% for each Target element. [Note—If samples are high in mineral content, rinse system well before introducing the Sample in order to minimize carryover.]

适用性要求：每个目标元素的漂移不大于20%【注意-如果样品中矿物质含量高，请在样品导入前先冲洗系统，以减少残留】