LC–MS/MS methods for determination of venetoclax in human plasma and cerebrospinal fluid

• Published in: Biomedical chromatography Vol. 37; no. 12; p. e5738
• Main Authors: Yang, Yan‐Ling, Qian, Zhou‐Yi, Zhao, Yang, Chen, Xiang‐Long, Huang, Qiong‐Ye, Guo, Yu‐Jiao, Sun, Lu‐Ning, Wang, Yong‐Qing
• Format: Journal Article
• Language: English
• Published: 01.12.2023
• ISSN: 0269-3879; 1099-0801; 1099-0801
• DOI: 10.1002/bmc.5738

We developed and validated sensitive MS/MS methods for the determination of venetoclax, an oral selective B‐cell lymphoma‐2 inhibitor, in human plasma and cerebrospinal fluid (CSF). Acetonitrile was used as protein precipitant. The mobile phase was 10 mM ammonium formate consisting of 0.1% formic acid and acetonitrile (40:60, v/v). The analytes were separated on an ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 μm) in 5 min. An API 4000 mass spectrometer was selected to quantify venetoclax and internal standard using m / z 868.3 → 636.3 and 876.3 → 644.3 under multiple response monitoring mode. In plasma, the calibration curve exhibited good linearity ranging from 20.0 to 5000 ng/mL, whereas in the CSF, the linear range was 0.500–100 ng/mL. The matrix effect of venetoclax and internal standard (venetoclax‐d8) was not obvious in both plasma and CSF. The inter‐ and intra‐run accuracy was within ±11.9%, and the inter‐ and intra‐run precision was below 13.6%. Both methods had no carryover, and the recovery was close to 100%. The validated methods were employed to quantify the concentrations of venetoclax in the plasma and CSF of patients diagnosed with chronic lymphocytic leukemia or acute myelogenous leukemia.