我们开发并验证了对人类血浆和脑脊液（CSF）中文替克唑（venetoclax）进行灵敏的MS/MS测定方法，文替克唑为一种口服选择性B细胞性淋巴瘤-2抑制剂。使用乙腈作为蛋白质沉淀剂。流动相为含有0.1％甲酸和乙腈（40：60，v/v）的10 mM 甲酸铵。在ACQUITY UPLC HSS T3色谱柱（2.1×50 mm，1.8 μm）上，在5分钟内分离分析物。选择API 4000质谱仪，使用多重反应监测模式的m/z 868.3→636.3和876.3→644.3进行定量文替克唑和内标的测定。在血浆中，标准曲线显示线性范围为20.0-5000 ng/mL，而在脑脊液中，线性范围为0.500-100 ng/mL。文替克唑和内标（文替克唑-d8）在血浆和脑脊液中的基质效应不明显。批间和内间准确度在±11.9％内，批间和内间精密度低于13.6％。两种方法均无串扰，并且回收率接近100％。验证的方法被用于定量诊断为慢性淋巴细胞白血病或急性髓系白血病的患者的血浆和脑脊液中文替克唑的浓度。 ©2023 John Wiley & Sons, Ltd.

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.© 2023 John Wiley & Sons, Ltd.