Analytical methods for residual solvents determination in pharmaceutical products.

Abstract

Residual solvents (RS) are not desirable substances in the final pharmaceutical product and their acceptable limits have been published in pharmacopoeias and ICH guidelines. The intension of this paper was to review and discuss some of the current analytical procedures including gas chromatographic (GC) and other alternative techniques which are used for residual solvents determination. GC methods have been developed to monitor this kind of impurities routinely. The most popular techniques of sample introduction into the gas chromatograph include direct injection, static or dynamic headspace, solid-phase microextraction and single drop microextraction. Different separation techniques like two dimensional chromatography or multicapillary chromatography were compared with classical separation mode with use of single capillary column. Also alternative methodologies for residual solvents testing were discussed in this review. In conclusions, gas chromatography-based procedures were described as the most appropriate because of the lowest detection limits, ease of sample preparation and specificity.