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

Abstract

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.

Population Pharmacokinetic Models of Venetoclax in Hematologic Malignancies: A Systematic Review

“…There have been developed and validated sensitive LC-MS/MS methods for the determination of VEN in human plasma and CSF. 39 We could determine its effective therapeutic concentration range, study the blood-brain barrier permeability of VEN and develop PPK models to determine optimal VEN dosing regimens required to achieve targeted CSF exposures. Although VEN is approved for adult patients, it is also used for pediatric patients in practical clinical applications.…”

Quantitative MALDI-MS and Imaging of Fungicide Pyrimethanil in Strawberries with 2-Nitrophloroglucinol as an Effective Matrix

“…For UPLC-MRM and MALDI-MS, PYM calibration solutions (5, 2, 1, 0.5, 0.25, 0.1, 0.05, 0.04, 0.025, 0.01 ppm) and a verification solution (0.75 ppm) were prepared in solvent (75:25 H 2 O/ACN), and separately in matrix-matched solution by isotopic dilution with 0.125 ppm PYM-SIL. For both sets of calibration solutions, the highest concentration standard calibration solution (5 ppm PYM + 0.125 ppm PYM-SIL) was first prepared from stock solutions.…”