DEVELOPMENT AND VALIDATION OF A HEADSPACE GAS CHROMATOGRAPHIC METHOD FOR DETERMINATION OF RESIDUAL SOLVENTS IN BOSENTAN MONOHYDRATE PURE DRUG

There are only few published reports on determination of residual solvents in the analytical method development and there exists no detailed guidelines. Residual solvents from the process in the manufacturing of pharmaceuticals are hazardous and cause serious problems, so must be removed. This is much effort in this work is focused on the determination of analytical method for the determination of residual solvents. Bosentan monohydrate pure drug, various solvents, Shimadzu GC-2010 with head space auto injector and Perkin Elmer – 500 with head space auto injector were used. The method development based on residual solvent properties and many trails conducted on conditions like column selection, carrier gas flow, oven temperature and diluent. A simple HS-GC method for the determination of residual solvents in Bosentan monohydrate using nitrogen as the carrier gas at 3.5mL/min with DB-624 (30 meters X 0.53 mm ID) as column using FID as detector was developed. The developed method was validated and parameters were to be found within the limits of USP. The retention time for residual solvents individually and in spiked standard solution was determined. The %RSD for six injections should be NMT15%. The percentage recovery ranges from 85-115%. The correlation coefficient R2 ≥ 0.999. The limit of detection and limit of quantification was found to be specific. Precision, method precision and intermediate precision was found to be within the acceptance limit. Finally the sample was tested for the presence of residual solvents mainly benzene as it is a class1 solvent and should be avoided.