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