Characterization of Forced Degradation Products of Lobeglitazone Sulfate by Liquid Chromatography–Tandem Mass Spectrometry and In Silico Toxicity Study—Development and Validation of Stability‐Indicating Reverse Phase Liquid Chromatographic Method

ABSTRACT This investigation aimed to demonstrate a method for separating, identifying, and characterizing very amounts of the degradation products of lobeglitazone sulfate using analytical techniques such as liquid chromatography and liquid chromatography–mass spectrometry. Under international conference on harmonization guideline Q1A(R2), the lobeglitazone sulfate was submitted to oxidative, hydrolytic, thermal, and photolytic stress conditions. The lobeglitazone sulfate was shown to be stable to photolytic, oxidative, and thermal stress conditions while being labile to hydrolytic (acidic and alkaline) stress conditions. A total of five degradation products were obtained, out of which degradation product I to degradation product IV were generated in basic chromatographic conditions, and degradation product V was generated in acidic conditions. High‐performance liquid chromatography was used to separate all the degradation products in a gradient mode using a C‐18 column. All the degradation products were identified by their fragmentation patterns and the masses found by liquid chromatography–tandem mass spectrometry studies. The previously unidentified degradation products were classified as (degradation product I to degradation product V). As per in silico toxicity studies the immunotoxicity potential of degradation product I, the peroxisome proliferator‐activated receptor gamma of degradation product III, and the carcinogenicity of degradation product IV were explored.