Validation of a generic analytical procedure for determination of residual solvents in drug substances

Abstract

A generic analytical procedure for determination of residual solvents in drug substances is described and validated. The procedure is based on methods described in the European and United States parmacopeias, but is faster than the compendial procedures. It is applicable both during drug development and for quality control in commercial manufacture. The method is accurate, linear and shows a satisfactory level of precision. The solvents included in the validation comprise the five class 1 solvents, 17 out of 27 class 2 solvents, 17 out of 27 class 3 solvents and three unclassified solvents according to ICH guideline Q3C. The solvents can be detected and quantified at levels at or below the ppm limits given in the guideline. In most cases the quantification limit is in the lower ppm range. A strategy is proposed to choose between water or N, N-dimethyl formamide as a diluent. The need for re-validation of the method, mandatory for quantitative procedures according to the European Pharmacopeia, is minimised when using the generic procedure.