Stability Indicating Methodology Development to Quantify Odevixibat Content: Application of LC-MS Methodology to Characterize Five Degradants of Odevixibat

Abstract

This investigation is concerned with development of HPLC technique that made use of a PDA sensor technology for the speedy assessment of odevixibat (OVBT) for the quality control of both their commercially marketed formulations as well as bulk form. The  ODS inertsil column (4.6 mm, 5 µm, 250 mm), mobile phase set up by mixing 0.1% formic acid and acetonitrile in a 60:40 volumes, rate  of flow of 1.0 mL/min and with detection using PDA at 223.7 nm was adopted for present procedure. Applying ICH specifications, the  HPLC-based OVBT assay strategy was validated successfully for linearity (5.00 to 30.00 µg/mL), sensitivity (LOD-0.60 µg/mL; LOQ-2.00  µg/mL), precision (0.207-0.600% RSD), accuracy (98.9-100.8% assay) and robustness (0.53-1.16% RSD). Numerous stress degradations  [acid, alkaline, reduction, oxidation, thermal, hydrolysis and photolytic] have been applied to odevixibat. The odevixibat is reported to  be prone to instability in oxidative stress and more persistent during photo stress. The HPLC-based odevixibat assay approach could be  implemented in quality assurance labs for the quantitative measurement of odevixibat in routine and stability sample analysis of  odevixibat bulk and odevixibat capsule doses. Five degradants [OVBT-DP1 (acid stress), OVBT-DP2 (alkali stress), OVBT-DP3 (oxidative  stress), OVBTDP4 (reduction stress) and OVBT-DP5 (heat stress)] were formed. By evaluating mass spectral data of five degradants  obtained through LC-MS approach, chemical structures of OVBT-DP1, OVBT-DP2, OVBT-DP3, OVBT-DP4 and OVBT-DP5 were elucidated.  The degradation possible mechanisms for all the five degradants formation are also suggested.