A sensitive ultra‐performance liquid chromatography‐tandem mass spectrometry method for the simultaneous quantification of assay and trace‐level genotoxic tosylate analogs (methyl and ethyl) in empagliflozin and its tablet dosage forms

Abstract

This study performed the simultaneous quantification of assay and two alkyl sulfonate (tosylate) analogs of empagliflozin (EGZ), specifically methyl 4‐methyl benzene sulfonate (MMBS) and ethyl 4‐methyl benzene sulfonate (EMBS) in EGZ, and its finished dosage form using an accurate and sensitive ultra‐performance liquid chromatography‐mass spectrometry method. The separation was achieved on a Waters Acquity BEH Shield RP18 (100 × 2.1 mm, 1.7 μm) column in gradient elution mode with 0.1% formic acid and acetonitrile as the mobile phases and a flow rate of 0.5 mL/min. For simultaneous quantification, the multiple reaction monitoring technique was utilized. The procedure was successfully validated in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The peak areas of both impurities, along with their concentrations, exhibited a good relationship with Pearson's correlation coefficient (R), which was >0.999 in the range of 0.3–6 ppm with an EGZ concentration of 2 mg/mL. The percentage recoveries from the limit of quantitation (LOQ) to 200% to the specification level were in the range of 94.82%–102.92%, whereas the percentage relative standard deviation (%RSD) was <2. Therefore, this method is rapid and accurate to quantify MMBS, EMBS, and EGZ assay simultaneously from the marketed tablet dosage forms of EGZ for commercial release and stability sample testing.

Analytical determination of ethylenediamine impurity in tripelennamine hydrochloride by gas chromatography–mass spectrometry using phthalaldehyde as the derivatizing agent

“…Nevertheless, the multiple reaction monitoring (MRM) approach incorporates the collision-induced dissociation cell, which breaks down the precursor ion and produces a product ion. Using double mass filtering in MRM mode, complete elimination of matrix interference is achievable, leading to enhanced sensitivity in quantifying lower limits of genotoxic impurities (Nakka et al, 2023;Nakka et al, 2024;Schreiber, 2010). To our knowledge, there has been no research on using GC-MS to identify EDs in TP.…”

Gas chromatography mass spectrometer determination of dimethylamine impurity in N,N‐dimethylformamide solvent by derivatization of N,N‐dimethylbenzamide with benzoyl chloride agent

“…Due to double mass filtering in MRM mode, matrix interference is eliminated and enhances the sensitivity to quantify the lower limits of genotoxic impurities (Andre, 2010;Goh et al, 2019;Nakka, Muchakayala, & Manabolu Surya, 2023;. The molecular weight of dimethylamine is 45, and its base peak is 44 m/z.…”