Unveiling the effect of chemical degradation on cyclic lipoglycopeptide Oritavancin using Orbitrap mass spectrometry

Abstract

Oritavancin is the second-generation approved semisynthetic cyclic lipoglycopeptide by the United States Food and Drug Administration (USFDA) for acute bacterial skin and skin-structure infections which serves as a last resort of treatment. Unlike other lipoglycopeptides, the stability behavior of Oritavancin was least explored, which is a prerequisite. The current study endeavors to elucidate the oxidative, hydrolytic, thermal and photolytic stability behavior of Oritavancin by exposing the drug to respective stress conditions. A simple liquid chromatography (LC) method was developed, where significant resolution between Oritavancin and the generated degradation products was achieved. In total 13 degradation products were identified under various stress conditions. Using LC-HRMS, MS/MS studies, the generated degradation products were identified and characterized. The intact mass for DP-2,7,12 was m/z 724.7219(2), DP-6,11, 13 was m/z 796.2672(2), DP-3,10 was m/z 643.6953(2). However isomeric mass as of ORT intact form was seen for DP-4 and unique masses were identified for DP-1,4,8,10 with m/z 725.4293(2), m/z 905.2965(2), m/z 863.2896(2), m/z 904.2890(2) respectively. The mechanistic fragmentation pathway for all the generated DP's were established and the plausible structure for the identified DP's were postulated based on the MS/MS data. According to the findings, Oritavancin is highly susceptible to photolytic, thermal and hydrolytic condition and least susceptible under oxidative condition. The developed reversed-phase high-performance liquid chromatographic (RP-HPLC) method was validated in accordance with ICH guidelines for Oritavancin using C₁₈ analytical reverse-phase column which could be utilised for routine quality control and therapeutic drug monitoring of Oritavancin.