LC-MS/MS Characterization of Forced Degradation Products of Repaglinide Quality by Design Approach for Stability-Indicating LC Method Development and Validation for Degradation Products

The current study demonstrates the characterization of unspecified degradation impurities of repaglinide by liquid chromatography-tandem mass spectrometry and development of stability-indicating test procedure for quantification of repaglinide and their organic impurities by application of Qbd approach. The use of QbD guidelines has proved to be realistic in the amplification of analytical methods. Identified analytical target profile (ATP) and critical analytical attributes (CAA). Based on the initial assessment, the important factors were finely tuned using Box-Behnken design with the help of numerical and graphical optimization. Evaluated stress studies under different types of conditions. The repaglinide was subjected to different forced degradation conditions such as acid, base, oxidation, thermal, and UV light to discover the stability-indicating competence of the proposed method. Significant degradation was detected during the oxidative stress condition. The repaglinide was well resolved from its impurities produced during the various stress conditions. The chromatographic optimization was attained on an acquity BEH; Shield-RP-C18100 mm x 2.1 mm; 1.7 μm with gradient elution mode at a flow rate of 0.3 ml min-1. The peaks were detected at 214 nm. The developed UHPLC method was validated as per the current ICH guidelines. The unspecified impurities were exemplified by comparing their collision-induced dissociation mass spectral data with that of repaglinide and the most probable degradation and fragmentation pathways were discussed.