Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography Methods

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 degradatio...

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Main Authors: Ali Ismail, Mohammad Haroun, Youssef Alahmad
Format: Article
Language:English
Published: University of Baghdad, College of Science for Women 2023-10-01
Series:مجلة بغداد للعلوم
Subjects:
Online Access:https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/7596
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author Ali Ismail
Mohammad Haroun
Youssef Alahmad
author_facet Ali Ismail
Mohammad Haroun
Youssef Alahmad
author_sort Ali Ismail
collection DOAJ
description 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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series مجلة بغداد للعلوم
spelling doaj-art-f521145bc4ed408bbdc1ce9fa8d056952025-08-20T03:22:34ZengUniversity of Baghdad, College of Science for Womenمجلة بغداد للعلوم2078-86652411-79862023-10-01205(Suppl.)10.21123/bsj.2023.7596Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography MethodsAli Ismail0Mohammad Haroun1Youssef Alahmad2Department of Pharmaceutical Chemistry and Drug Quality Control, Faculty of Pharmacy, Tishreen University, Syria. Department of Pharmaceutical Chemistry and Drug Quality Control, Faculty of Pharmacy, Tishreen University, Syria.Department of Pharmaceutical Chemistry and Drug Quality Control, Faculty of Pharmacy, Arab Private University for Science and Technology and Al Baath University, Syria. 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. https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/7596 Dapagliflozin, Degradation products, Impurity profile, LC/MS, Preparative chromatography.
spellingShingle Ali Ismail
Mohammad Haroun
Youssef Alahmad
Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography Methods
مجلة بغداد للعلوم
Dapagliflozin, Degradation products, Impurity profile, LC/MS, Preparative chromatography.
title Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography Methods
title_full Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography Methods
title_fullStr Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography Methods
title_full_unstemmed Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography Methods
title_short Qualitative and Quantitative Determination of Dapagliflozin Propanediol Monohydrate and Its Related Substances and Degradation Products Using LC-MS and Preparative Chromatography Methods
title_sort qualitative and quantitative determination of dapagliflozin propanediol monohydrate and its related substances and degradation products using lc ms and preparative chromatography methods
topic Dapagliflozin, Degradation products, Impurity profile, LC/MS, Preparative chromatography.
url https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/7596
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AT mohammadharoun qualitativeandquantitativedeterminationofdapagliflozinpropanediolmonohydrateanditsrelatedsubstancesanddegradationproductsusinglcmsandpreparativechromatographymethods
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