International Journal of Pharma Research & Review, Oct 2013; 2(10):25-40 Manish Kapil et.al, IJPRR 2013; 2(10) 25 Review Article A Review: Residual Solvents and Various Effective Gas Chromatographic Techniques in the Analysis of Residual Solvent *Manish Kapil 1 , Suman Lata 2 1. Department of Pharmaceutical Analysis, ASBASJSM College of Pharmacy, Bela Ropar -140001, Punjab, India. 2. Department of Pharmaceutical Chemistry, ASBASJSM College of Pharmacy, Bela Ropar -140001, Punjab, India. ________________________________________________________________________________________________________________________________________________________ ABSTRACT 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 limit of residual solvents and to discuss various Gas Chromatographic (GC) techniques to analyze about all the residual solvents mentioned in ICH guideline, Q3C. Gas Chromatography is coupled with various other techniques to increase the sensitivity of the method. Various 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 chromatography- mass spectrometry (HSGC-MS), flow- modulation technique for gas chromatography, thermal desorption- headspace gas chromatography (TD-HSGC), headspace gas chromatography- solid phase microextraction (HSGC-SPME), dual column gas chromatography, multiple headspace- single drop microextraction (MHS-SDME) and headspace gas chromatography- solid phase microextraction- mass spectrometry (HSGC-SPME-MS). Application of various gas chromatographic techniques to some drugs or pharmaceutical preparations are also covered under the study. Keywords: Carrier gas, gas chromatography, headspace, residual solvents Received 09 August 2013 Received in revised form 31 August 2013 Accepted 03 Sept 2013 *Address for correspondence: Manish Kapil Department of Pharmaceutical Analysis ASBASJSM College of Pharmacy, Bela Ropar -140001, Punjab, India. E-mail: manishkapil444@gmail.com _________________________________________________________________________________________________________________________________________________________ INTRODUCTION Residual Solvents According to USP residual solvents are organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products. These are not completely removed by practical manufacturing techniques [1]. Since there is no therapeutic benefit from residual solvents, all of these should be removed to the extent possible to meet product specifications, good manufacturing practices, or other quality-based requirements [2]. Over 60 residual solvents are included in USP. Testing for residual solvents in raw materials may be highly recommended as this solvent may be carried through the process and remain in the finished product. Early in the process, control is usually more cost-effective compared to remediation or even rejection of final product [1]. Regulation of Residual Solvents testing Since the late 1970s, different investigations were done for the control of residual solvents. In 1997, limit contents for residual solvents in relation to their permitted daily exposure (PDE) were