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 a...

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Bibliographic Details
Published in:Journal of analytical chemistry (New York, N.Y.) N.Y.), 2023-04, Vol.78 (4), p.522-534
Main Authors: Dhiman, Vivek, Ahirwar, Sourabh, Chaganti, Sowmya, Gananadhamu, S.
Format: Article
Language:English
Subjects:
Acetic acid
Acetonitrile
Acidic oxides
Ammonium acetate
Analytical Chemistry
Azobisisobutyronitrile
Cancer
Chemistry
Chemistry and Materials Science
Degradation
High performance liquid chromatography
High resolution
Hydrogen peroxide
Ions
Mass spectrometry
Methods
Room temperature
Scientific imaging
Toxicity
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Summary: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 (H 2 O 2 at room temperature and 2,2-azobisisobutyronitrile at 40°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.
ISSN:1061-9348
1608-3199
DOI:10.1134/S1061934823040081