From Limits to Detection: Gas Chromatography as a Tool for Residual Solvents Analysis

Residual solvents are the undesired substances (solvents) used or produced during the manufacture of a excipients, drug or pharmaceutical formulation and are not completely removed by practical methods in the final finished product. These solvents can be toxic in nature. Therefore, analysis of residual solvents becomes a necessary tool for the quality control of pharmaceuticals. The acceptable limits for these substances are given in ICH guidelines (Guideline for Residual solvents, Q3C). The intension of this paper is to review toxic limits of residual solvents and to discuss various Gas Chromatographic (GC) techniques to analyze about all the residual solvents mentioned in ICH guidelines, Q3C. Gas Chromatography is coupled with various other techniques to increase the sensitivity of the method. Various analytical techniques included in this study are gas chromatography, direct injection method, headspace gas chromatography(HSGC), static headspace sampling, dynamic headspace sampling, fast gas chromatography, headspace gas chromatography coupled flame ionisation detector (HSGC-FID), head space gas chromatographymass spectrometry (HSGC-MS), flow- modulation technique for gas chromatography, thermal desorption- headspace gas chromatography (TDHSGC), headspace gas chromatography- solid phase microextraction (HSGC-SPME), dual column gas chromatography, multiple headspacesingle drop microextraction (MHS-SDME) and headspace gas chromatography- solid phase microextraction- mass spectrometry (HSGCSPME-MS). Application of various gas chromatographic techniques for the quantification of a few drugs or pharmaceutical preparations are also covered under this review.