Development of methods for determining the content of residual organic solvents in a new pharmaceutical substance of 3-(1H-benzimidazol-2-yl)-1,2,2-trimethylcyclopentane-carboxylic acid

Abstract

Objective. Organic solvents, which often have toxic and/or carcinogenic properties, are used at all stages of the production of pharmaceutical substances - synthesis, isolation and purification - and are not completely removed after the completion of the technological process. The presence of even extremely small amounts of such compounds in medicines can be dangerous for patients. The article presents the results of the development of a method for determining the content of residual organic solvents (ROS) - ethanol, toluene and dimethylformamide - in a new active pharmaceutical ingredient (API) 3-(1H-benzimidazol-2-yl)-1,2,2-trimethylcyclopentane-carboxylic acid by gas chromatography. Materials and methods. Static vapor phase analysis was used to identify and to quantify residual organic solvents. It was determined by the internal standard method using a Shimadzu GC-2014ATF/SPL gas chromatograph with an AOC-6000Plus autosampler; PID detection. Isobutyl alcohol was used as an internal standard. Results. The developed method was used to determine the content of residual organic solvents in the validation series of the new pharmaceutical substance 3-(1H-benzimidazol-2-yl)-1,2,2-trimethylcyclopentane-carboxylic acid. The method was validated in accordance with the requirements of the State Pharmacopoeia of the Russian Federation. Conclusion. The developed method is suitable for further use in quality control in the production of 3-(1H-benzimidazol-2-yl)-1,2,2-trimethylcyclopentane-carboxylic acid.