溶剂 PDE（mg/天） 浓度限度（ppm）
乙晴 4.1 410 氯苯 3.6 360 氯仿 0.6 60 环己烷 38.8 3880 1,2－二氯乙烯 18.7 1870 二氯甲烷 6.0 600 1,2－二甲亚砜 1.0 100 N,N－二甲乙酰胺 10.9 1090 N,N－二甲基甲酰胺 8.8 880 1,4－二恶烷 3.8 380 2－乙氧基乙醇 1.6 160 乙二醇 6.2 620 甲酰胺 2.2 220 正己烷 2.9 290 甲醇 30.0 3000 2－甲氧基乙醇 0.5 50 甲基丁酮 0.5 50 甲基环己烷 11.8 1180 二氯甲烷 6.0 600 N-甲基吡咯烷酮 5.3 530 硝基甲烷 0.5 50 吡啶 2.0 200 二氧噻吩烷 1.6 160 四氢呋喃 7.2 720 四氢萘 1.0 100 甲苯 8.9 890 1,1,2-三氯乙烯 0.8 80 二甲苯* 21.7 2170 *通常为60% m-二甲苯，14% p-二甲苯，9% o-二甲苯和17%乙基苯。
Class 3
Class 3 residual solvents (Table 3) may be regarded as less toxic and of lower risk to human health than Class 1 and Class 2 residual solvents. Class 3 includes no solvent known as a human health hazard at levels normally accepted in pharmaceuticals. However, there are no long-term toxicity or carcinogenicity studies for many of the residual solvents in Class 3. Available data indicate that they are less toxic in acute or short-term studies and negative in genotoxicity studies. 第3类
第3类残留溶剂(表3)可被视为低毒并较第1类和第2类残留溶剂对人体健康的危害风险更小。第三类溶剂包括人们认为在药物中以一般量存在时对人体无害的溶剂，但该类溶剂中许多尚未进行长期毒性或致癌研究。现有数据表明，它们在急性或短期研究和阴性遗传毒性研究中表现为低毒。
It is considered that amounts of these residual solvents of 50 mg per day or less (corresponding to 5000 ppm or 0.5% under Option 1) would be acceptable without justification. Higher amounts may also be acceptable, provided that they are realistic in relation to manufacturing capability and good manufacturing practice. For the purposes of this Pharmacopeia, when a manufacturer has received approval from a competent regulatory authority for such a higher level of residual solvent, it is the responsibility of that manufacturer to notify the USP regarding the identity of this solvent and the approved residual solvent limit in the article. The USP will then address this topic in the individual monograph. If a Class 3 solvent limit in an individual monograph is greater than 50 mg per day, that residual solvent should be identified and quantified. The procedures described in the section Identification, Control, and Quantification of Residual Solvents in this general chapter, with appropriate modifications to the standard solutions, are to be applied wherever possible. Otherwise an appropriate validated procedure is to be employed.
据认为，每日50mg或更少的残留溶剂量无须论证即可接受（用方法１计算。即5000ppm或0.5％）。如果能够反映生产能力和GMP的实际情况，更大的量也可接受。该药典旨在，当一个制造商从一个权
威管理机构通过一个更高的限度，该制造商有责任通知美国药典关于对该产品所批准的的残留溶剂限度及理由。美国药典将会在个别专论中解决此主题。如有一个三类溶剂在个别专论的限度大于每天50mg，该残留溶剂应被鉴别并量化。在本章节残留溶剂鉴别，控制及量化中所述的方法，对标准溶液作合适的修改，将被尽可能地应用，否则一个适当的验证方法将被使用。
Acetic acid 乙酸 Heptane庚烷
Acetone 丙酮 Isobutyl acetate乙酸异丁酯 Anisole苯甲醚 Isopropyl acetate乙酸异丙酯 1-Butanol 1-丁醇 Methyl acetate乙酸甲酯 2-Butanol 2-丁醇 3-Methyl-1-butanol 3-甲基-1-丁醇 Butyl acetate乙酸丁酯 Methylethylketone甲乙酮
tert-Butylmethyl ether甲基叔丁基醚 Methylisobutylketone甲基异丁酮 Cumene异丙苯 2-Methyl-1-propanol 2-甲基-1-丙醇 Dimethyl sulfoxide二甲基亚砜 Pentane戊烷 Ethanol 乙醇 1-Pentanol 1-戊醇 Ethyl acetate 乙酸乙酯 1-Propanol 1-丙醇 Ethyl ether 乙醚 2-Propanol 2-丙醇 Ethyl formate甲酸乙酯 Propyl acetate乙酸丙酯 Formic acid甲酸
Other Residual Solvents
The residual solvents listed in Table 4 may also be of interest to manufacturers of drug substances, excipients, or drug products. However, no adequate toxicological data on which to base a PDE was found Table 4. Other Residual Solvents
(for which no adequate toxicological data was found) 其他残留溶剂
以下溶剂在表4中列出，在辅料、原料药和制剂生产中也许会被生产商采用，但尚无足够的毒理学数据，故无PDE值。 表4 无足够毒理学数据的溶剂
1,1-二乙氧基丙烷 甲基异丙酮 1,1-二甲氧基甲烷 甲基四氢呋喃 2,2-二甲氧基丙烷 石油醚 异辛烷 三氯乙酸 异丙醚 三氟乙酸 IDENTIFICATION, CONTROL, AND QUANTIFICATION OF RESIDUAL SOLVENTS
Whenever possible, the substance under test needs to be dissolved to release the residual solvent. Because the USP deals with drug products, as well as active ingredients and excipients, it may be acceptable that in some cases, some of the components of the formulation will not dissolve completely. In those cases, the drug product may first need to be pulverized into a fine powder so that any residual solvent that may be present can be released. This operation should be performed as fast as
possible to prevent the loss of volatile solvents during the procedure. 残留溶剂的鉴别，控制和量化
只要有可能，待测品需要被溶解以释放残留溶剂。因USP涉及制剂，原料药成分及辅料，因此处方中一些成分不能完全溶解的情况是可以接受的。在这种情况下，药品需要首先制成精细粉末以便可能存在的残留溶剂能够释放。该操作应尽快以防止在操作过程造成挥发溶剂损失。
Note—The organic-free water specified in the following procedures produces no significantly interfering peaks when chromatographed.
【注-以下程序指明的去有机水在色谱中对峰没有明显干扰。】
Class 1 and Class 2 Residual Solvents
The following procedures are useful to identify and quantify residual solvents when the information regarding which solvents are likely to be present in the material is not available. When the information about the presence of specific residual solvents is available, only Procedure C is needed to quantify the amount of residual solvents present. A flow diagram for the application of the residual solvent limit tests is shown in Figure 1.
一类和二类残留溶剂
以下程序在溶剂可能存在于物料中不适用时对残留溶剂的鉴别和量化是有帮助的。当明确的特定残留溶剂的存在是适用的，只有方法C能用于确定残留溶剂存在的数量。下图1为残留溶剂限量检测方法流程图。