Application of GC-MS and LC-MS techniques for direct analysis of amines in pharmaceutical substances

Abstract

Organic volatile chemicals such as amines are often not completely removed by practical manufacturing techniques and consequently their low levels are present in most pharmaceuticals. Based on good manufacturing practices and for the safety of the patients the level of hazardous for human health amines in pharmaceuticals have to be strictly controlled. Moreover, analysis of volatile amines in drug product has become recently an emerging topic of interest for analytical chemists since such residual impurities as: secondary amines, tertiary amine and other amine derivatives (in certain condition) have been reported to be a precursors of carcinogenic N-nitrosamines (NAs). In this study we present five new methods for control of such amines as: tert-butylamine (TBA), pyrrolidine, 4-fluoroaniline (4-FA), diisopropyl-ethylamine (DIPEA) and tetrabutylammonium hydrogensulfate (TBAHS) in pharmaceutical active ingredients (APIs) using GC-MS and LC-MS techniques. The validations results clearly demonstrate that the analytical procedures are suitable for their intended purpose. All revealed validations results meet the requirements of the ICH Q2R1 validation guidelines and the Q3A R2 guideline for residual impurities.