Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography Methods
DOI:
https://doi.org/10.21123/bsj.2023.7596Keywords:
Dapagliflozin, Degradation products, Impurity profile, LC/MS, Preparative chromatography.Abstract
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.
Received 29/6/2022
Revised 10/9/2022
Accepted 11/9/2022
Published Online First 20/3/2023
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