Photolytic and Oxidative Degradation Behavior of Anticancer Drug Venetoclax: Characterization of New Degradation Products Using High Resolution Mass Spectrometry

Venetoclax (VEN), an anticancer drug, was subjected to photolytic and oxidative degradation studies. The comprehensive degradation profiling of VEN in both conditions was reported. All the degradation products (DPs) were separated on reversed phase HPLC by employing an X-Bridge C18 column with ammonium acetate (pH adjusted to 3.20 with acetic acid) and organic solvent mixture of methanol with acetonitrile in the ratio of 90 : 10 as mobile phase. The overall results showed that it underwent significant degradation upon exposure to light (acidic pH) and oxidative (H2O2 at room temperature and 2,2-azobisisobutyronitrile at 40 degrees C) conditions. A total of fifteen new DPs were identified with high resolution mass spectrometry data generated from liquid chromatography-high resolution mass spectrometry system. This information was used for the establishment of a complete degradation pathway of VEN. Additionally, in silico properties, viz., absorption, distribution, metabolism, excretion and toxicity (ADMET), of VEN and its DPs were predicted with admetSAR software.