Development of an HPLC-UV Method to Assay Empagliflozin Tablets and Identification of the Major Photoproduct by Quadrupole Time-of-Flight Mass Spectrometry

Abstract

Diabetes is a set of metabolic disorders that affect >400 million individuals worldwide. Empagliflozin belongs to the gliflozin class and is used orally to treat type 2 diabetes. In this study, a simple stability-indicating HPLC-UV method was developed to assay empagliflozin tablets and its main photoproduct was identified by high-resolution mass spectrometry. The mobile phase, which was optimized by Central Composite Design, was composed of methanol, acetonitrile and purified water (60:5:35 v/v), at a flow rate of 1 mL min−1. The calibration curve was linear in the range of 5–150 μg mL−1. All the validation parameters were met and the method was specific, even in the presence of degradation products. In the forced degradation study, empagliflozin standard and empagliflozin tablets were submitted to several conditions (acidic, alkaline, neutral and oxidant media, thermal, photolytic and humidity), and empagliflozin showed instability under all these conditions. A degradation product generated after drug exposure to ultraviolet C radiation was isolated and analyzed by quadrupole time-of-flight mass spectrometry, and the results suggested that empagliflozin undergoes decomposition by a dechlorination pathway. In silico toxicity was predicted for the degradation product, which showed a high risk of genotoxicity and hepatotoxicity.

RP-HPLC Method Development and Validation for an Estimation of Empaglifl ozin from Bulk and Pharmaceutical Dosage Form

“…15 Empaglif lozin can be estimated using limited highperformance liquid chromatography (HPLC), reverse-phase high-performance liquid chromatography (RP-HPLC), and ultraviolet (UV) methods, according to a survey of the relevant published research. [16][17][18][19][20][21][22][23][24][25][26][27][28] This study was undertaken to determine the best RP-HPLC technique aimed at determining the quantity of empagliflozin in both bulks and pharmaceutical dosage forms. The recommendations laid out by ICH were used to perform the technique validation.…”

Novel UV Spectroscopic Methods for Simultaneous Assessment of Empagliflozin, Linagliptin and Metformin in Ternary Mixture

“…Trijardy XR ® consisting of empagliflozin, linagliptin, and metformin hydrochloride formulated as tablets (extended release) is a fixed-dose combination that improves glycemic control in individuals with diabetes mellitus (type 2) if given in conjunction with controlled diet and regular workout. [9][10][11] Literature survey disclosed numerous analytical approaches for the assessment of EPZ, LGT and MTH independently and in combined dosage form by means of UV spectrophotometry, [12][13] HPLC, [14][15][16][17][18][19][20] HPTLC. [21][22][23][24] Moreover, few methods were described for the estimation of EPZ, LGT and MTH in combined formulation/synthetic mixture using HPLC, [25][26][27][28][29] and HPTLC.…”