若所有措施均不能降低残留溶剂的水平，厂方应提供其尝试降低残留溶剂以符合指导原则所做工作的总结报告，并以利弊分析报告证明允许该制剂存在的较高水平的残留溶剂。
ANALYTICAL PROCEDURES
Residual solvents are typically determined using chromatographic techniques such as gas chromatography. Compendial methods for testing for residual solvent content are described under the section Identification, Control, and Quantification of Residual Solvents in this general chapter. The General Notices discuss the use of other methods in special circumstances (see 6.30. Alternative and Harmonized Methods and Procedures). If Class 3 solvents are present, a nonspecific method such as loss on drying may be used.
分析方法
残留溶剂通常用色谱技术，如用GC法测定。药典规定对该章节检测的残留溶剂含量需要进行鉴别控制和定量。通则规定在特殊情况下使用其他方法（见6.30.替换统一方法和操作步骤）。若仅存在第三类溶剂；可用非专属性的方法如干燥失重来检查。
REPORTING LEVELS OF RESIDUAL SOLVENTS
残留溶剂的报告水平
Manufacturers of pharmaceutical products need certain information about the content of residual solvents in drug substances or excipients in order to meet the criteria of this general chapter. The following statements are given as acceptable examples of the information that could be provided from a supplier of drug substances or excipients to a pharmaceutical manufacturer. The supplier might choose one of the following as appropriate:
医药产品生产商需要了解有关药物或辅料中残留溶剂含量的信息，以符合本指导原则的标准。以下阐述了药物或辅料供应商应提供给制剂生产商的信息的一些例子。供应商应选择以下一项：
〃Only Class 3 solvents are likely to be present. Loss on drying is less than 0.5%.
〃Only Class 2 solvents X, Y, ... are likely to be present. All are below the Option 1 limit. (Here the supplier would name the Class 2 solvents represented by X, Y, ...)
〃Only Class 2 solvents X, Y, ... and Class 3 solvents are likely to be present. Residual Class 2 solvents are below the Option 1 limit and residual Class 3 solvents are below 0.5%.
〃仅可能存在第三类溶剂，干燥失重小于0.5％。 〃仅可能存在第二类溶剂，X、Y……
全部应低于方法1的限度。（这里供应商应将第二类溶剂用X、Y……来表示）
〃仅可能存在第二类溶剂X、Y……和第三类溶剂，残留的第三
类溶剂低于方法1的限度，残留的第三类溶剂低于0.5％。
The phrase ―likely to be present‖ as used in the above examples refers to the solvent used or produced in the final manufacturing step and to solvents that are used or produced in earlier manufacturing steps and not removed consistently by a validated process.
If Class 1 solvents are likely to be present, they should be identified and quantified. If solvents of Class 2 or 3 are present at greater than their Option 1 limits or 0.5%, respectively, they should be identified and quantified.
上述例子中的“可能存在”系指最后一步工艺使用或产生的溶剂和较前几步工艺使用或产生的溶剂经验证不能全部除尽。 如果可能存在第一类溶剂，应进行鉴定并定量。如果第二类溶剂高于方法1的限度或第三类溶剂高于0.5％，应鉴定并定量。
LIMITS OF RESIDUAL SOLVENTS
残留溶剂的限度
Class 1 (solvents to be avoided) 1类(应避免的溶剂)
Class 1 residual solvents (Table 1) should not be employed in the manufacture of drug substances, excipients, and drug products because of the unacceptable toxicities or deleterious environmental effects of these residual solvents. However, if their use in order to produce a medicinal product with a significant therapeutic advance is unavoidable, their levels should be restricted as shown in Table 1, unless otherwise stated in the individual monograph. The solvent 1,1,1-trichloroethane is included in Table 1 because it is an environmental hazard. The stated limit of 1500 ppm is based on a review of safety data.
1类残留溶剂(表1)因其具有不可接受的毒性或对环境造成公害，第一类溶剂在原料药、辅料及制剂生产中不应该使用。但是，为了生产一种有特殊疗效的药品而不得不使用时，除非经过其他论证，否则应按表1控制，1，1，1－三氯乙烷因会造成环境公害列入表1，其限度1500ppm是基于安全性数据而定的。
When Class 1 residual solvents are used or produced in the manufacture or purification of a drug substance, excipient, or drug product and are not removed by the process, these solvents should be identified and quantified. The procedures described in the section Identification, Control, and Quantification of Residual Solvents in this general chapter are to be applied wherever possible. Otherwise an appropriate validated procedure is to be employed.
当1类残留溶剂被使用或在原料药，辅料，制剂的生产、精制中产生且在生产过程中没有去除，这些溶剂应被鉴别并确认。描述于本章节残留溶剂的鉴别、控制及量化中的方法适用于任何可能的情况下。否则一个适当的验证程序将被使用。
Table 1. Class 1 Residual Solvents (solvents that should be avoided)
表1 药物制剂中含第一类溶剂的限度（应避免使用）
溶剂 浓度限度（ppm） 备注 苯 2 致癌物 四氯化碳 4 毒性及环境公害 1,2－二氯乙烷 5 毒性 1,1－二氯乙烷 8 毒性 1,1,1－三氯乙烷 1500 环境公害
Class 2
Class 2 residual solvents (Table 2) should be limited in drug substances, excipients, and drug products because of the inherent toxicities of the residual solvents. PDEs are given to the nearest 0.1 mg per day, and concentrations are given to the nearest 10 ppm. The stated values do not reflect the necessary analytical precision of the determination procedure. Precision should be determined as part of the procedure validation.
2类
2类残留溶剂(表2) 应限制的溶剂，由于其具毒性，在制剂中应予限制，规定 PDE约 0.1mg／天，浓度约10ppm。所列值不能反映测定所必需的分析精度，精度应为方法论证的一部分。
If Class 2 residual solvents are present at greater than their Option 1 limits, they should be identified and quantified. The procedures described in the section Identification, Control, and Quantification of Residual
Solvents in this general chapter are to be applied wherever possible. Otherwise an appropriate validated procedure is to be employed.
如果2类溶剂比方法1的限度高，这些溶剂应被鉴别并定量分析。描述于本章节残留溶剂的鉴别、控制及量化中的方法适用于任何可能的情况下。否则一个适当的验证程序将被使用。
[Note—The following Class 2 residual solvents are not readily detected by the headspace injection conditions described in the section Identification, Control, and Quantification of Residual Solvents in this general chapter: formamide, 2-ethoxyethanol, 2-methoxyethanol, ethylene glycol, N-methylpyrrolidone, and sulfolane. Other appropriate validated procedures are to be employed for the quantification of these residual solvents. Such procedures shall be submitted to the USP for review and possible inclusion in the relevant individual monograph. In addition, USP Residual Solvent Class 2—Mixture C RS can be used to develop an alternative procedure. ]
[注释-下面的2类残留溶剂不易被描述于本章节中的残留溶剂的鉴别、控制及量化中的顶空进样条件所检测：甲酰胺，2－乙氧基乙醇，2－甲氧基乙醇，乙二醇，N-甲基吡咯烷酮及二氧噻吩烷。其它合适的验证方法将被用于这些残留溶剂的量化。这些方法应递交给美国药典审核并可能包含于相关的个别专论中。此外，USP第2类残留溶剂- CRS混匀物可以用于发展替代程序。]
表2 药品中第二类溶剂Table 2. Class 2 Residual Solvents