Estimation of Nine Organic Volatile Impurities in Bulk Dapagliflozin propandiol hydrate and Dosage forms from different sources using a new developed HS-GC-FID method

Abstract

As a part of impurity profiling, we aimed in this work to determine the content of organic volatile impurities (OVIs), commonly known as residual solvents (RSs), in different sources of dapagliflozin propandiol monohydrate as raw materials and marketed film-coated tablets. For that, a novel HS-GC-FID method has been developed and validated for determination of methanol, ethanol, ether, acetonitrile, dichloromethane, n-hexane, ethyl acetate, tetrahydrofuran and toluene. Dimethyl sulfoxide DMSO was used us diluent. The separation was achieved on Agilent DB-624 (30m, 0.530mm, 3.0µm) column and nitrogen as carrier gas with a total run time of 20 minutes. Solvents peaks indicate high resolution. Correlation factor R2 was estimated for each solvent and values ranged from 0.9990 to 0.9995. Estimation of limit of detection of these nine solvents showed that developed method was more sensitive than published method. The percentage recoveries calculated and the values ranged from 100.2% to 111.54%. The methods has been found to be simple, very sensitive, rugged, reliable and reproducible for the quantitation of these solvents in different sample of dapagliflozin raw materials and marketed tablets. Ethanol (class 3) and n-hexane (class 2) were detected in unacceptable level in some marketed samples.