Characterization of Oxidative Degradation Product of Canagliflozin by LC-MS/MS

Advances in Pharmacology and Pharmacy Vol. 10(3), pp. 173 - 180
DOI: 10.13189/app.2022.100303
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Vijaya Vichare 1,*, Vishnu Choudhari 2, Vrushali Tambe 1, Shashikant Dhole 1
1 PES Modern College of Pharmacy (for ladies), Moshi, Pune 412105, Maharashtra, India
2 School of Pharmacy, MIT World Peace University, Pune, Maharashtra, India

ABSTRACT

Prior knowledge of chemical stability of drugs directs path for right selection of dosage form, excipients, storage conditions and packaging material. Literature survey revealed that, there are analytical methods reported for quantification and stability indication of Canagliflozin in bulk and formulation. But there is not much information available about the degradation products generated under different stability conditions. With this background, characterization of oxidative degradation product of Canagliflozin was successfully carried out by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) studies. Degradation product was generated by forced degradation, according to International Conference on Harmonization (ICH) guidelines. Degradation product was separated from Canagliflozin by validated reverse phase (RP)-HPLC method using C18 column and Acetonitrile: Water pH 3.0 adjusted with 0.1% formic acid (70: 30, v/v) as mobile phase at a flow rate of 1mL/min. The developed RP-HPLC method was validated for different parameters as per ICH guidelines. The method was found to be linear in a range of 25-225 μg/mL. The developed method was found to be specific, accurate, precise, sensitive and robust. The marketed tablet formulation was analyzed by the developed method and the percent drug content was found to be 100.09 ± 1.96 % w/w. Separated degradation product was characterized by LC-MS/MS studies. From LC-MS/MS data probable structure of the degradation product was interpreted and the mechanism of degradation was proposed. The probable structure of degradation product was proposed as2-(4-Fluorophenyl)-5-(methyl) thiophene-1-one. The mechanism of degradation was proposed by S-oxidation of thiophene ring to form thiophene oxide. This information will help synthetic chemists to design a synthesis scheme for the oxidative degradation product, which can be used as a reference standard for impurity profiling. It is also suggested to protect CN from oxidative conditions for improved stability.

KEYWORDS
Canagliflozin, RP-HPLC Method, Oxidative Degradation, LC-MS/MS, Characterization

Cite This Paper in IEEE or APA Citation Styles
(a). IEEE Format:
[1] Vijaya Vichare , Vishnu Choudhari , Vrushali Tambe , Shashikant Dhole , "Characterization of Oxidative Degradation Product of Canagliflozin by LC-MS/MS," Advances in Pharmacology and Pharmacy, Vol. 10, No. 3, pp. 173 - 180, 2022. DOI: 10.13189/app.2022.100303.

(b). APA Format:
Vijaya Vichare , Vishnu Choudhari , Vrushali Tambe , Shashikant Dhole (2022). Characterization of Oxidative Degradation Product of Canagliflozin by LC-MS/MS. Advances in Pharmacology and Pharmacy, 10(3), 173 - 180. DOI: 10.13189/app.2022.100303.

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