Development and Validation of Gas Chromatographic Method for Residual Solvents Determination in Difenoxin Hydrochloride
Residual solvents in pharmaceuticals are termed as organic Volatile Impurities. These are the chemicals that are used in the manufacture of drug substance or excipients or use in the preparation of final formulation. Analysis of organic volatile impurities is of key importance for Active Pharmaceutical Ingredients (API). Most of the available methods use liquid chromatography which could be expensive and time consuming. The determination of Organic volatile impurities by Headspace GC method was developed and validated for Difenoxin hydrochloride bulk drug and for its seven residual solvents namely Dimethyl Formamide (DMF), Dichloromethane (DCM), Acetone, Toluene, Ethanol Methanol and Benzene. Analysis was performed on Agilent GC 7820A FID detector and Chemstation software with auto injector. Carrier gas Helium was used with constant flow rate of 2.5mL/min as carrier gas and the separation of residual solvents were achieved on DB-5 column. The thermostat temperature was 125 °C for 20 minute for each vial and after the equilibration the vials were pressurized and injected on GC column. FID detector was used for detection. We used ICH parameters to validate the developed method. The parameter for which the method was validated included specificity, limit of detection and quantification, linearity, precision, accuracy and robustness. The method was successfully used to quantify the levels of specified limit for residual solvents in Difenoxin hydrochloride bulk drug.