Method Development and Validation for the Determination of Residual Solvents in Racecadotril by Gas Chromatography

Background: The presence of residual solvents in pharmaceuticals can be a potential risk factor to human health because of its toxicity. Gas chromatography is used for its excellent separation abilities and lower limit of detection. Racecadotril, an antidiarrheal drug, is reported having four residual solvents, namely n-Hexane, isopropyl alcohol, toluene, and dimethylformamide. Estimation of the amount of these solvents in active pharmaceutical ingredients to ensure that they are within the permissible limits as per ICH guidelines is necessary. Objective: To develop and validate a new, simple, and sensitive gas chromatographic method for simultaneous determination of n-Hexane, isopropyl alcohol, toluene, and dimethylformamide in racecadotril. Methods: The residual solvents of racecadotril were estimated using a gas chromatographic method by direct injection using FID as a detector. This method employed a 30-meter long DB-FFAP nitroterephthalic-acid-modified polyethene glycol column with 0.53 mm in inner diameter and 1 μm film thickness. The separation was achieved using nitrogen as the carrier gas at a flow rate of 2.8 mL/min using a split ratio of 1:10. Results: The peak shape for all the residual solvents from racecadotril was symmetric with excellent resolution eluting at reasonable retention time. The limit of detection of n-Hexane, isopropyl alcohol, Toluene, and dimethylformamide was found to be 6, 27, 14, and 42 ppm, respectively. The developed method exhibited excellent linearity for each residual solvents in the range studied. Conclusion: The developed gas chromatographic method is simple, specific, precise, accurate, and sensitive. Hence, the method can be successfully used in in the pharmaceutical companies and research laboratories for simultaneous determination of residual solvents in racecadotril active pharmaceutical ingredients.