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.
Dapagliflozin is a novel sodium-glucose cotransporter type 2 inhibitor. This work aims to develop a new validated sensitive RP-HPLC coupled with a mass detector method for the determination of dapagliflozin, its alpha isomer, and starting material in the presence of dapagliflozin major degradation products and an internal standard (empagliflozin). The separation was achieved on BDS Hypersil column (length of 250mm, internal diameter of 4.6 mm and 5-μm particle size) at a temperature of 35℃. Water and acetonitrile were used as mobile phase A and B by gradient mode at a flow rate of 1 mL/min. A wavelength of 224nm was selected to perform detection using a photo diode array detector. The method met the requirement of the International Conference on Harmonisation for Registration of Pharmaceuticals for Human Use (ICH) for validation. The molecular weight of impurities and degradation products was estimated using positive ESI-MS. Fifteen impurities were detected during the analysis of dapagliflozin APIs and the brand Farxiga ® and some generic products. Three of fifteen detected impurities (H, J and K) exceeded the impurities acceptable limits 0.1%. Those impurities were isolated using new preparative chromatography then characterized using elemental analysis, FTIR and NMR.
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