Quantification of Venetoclax for Therapeutic Drug Monitoring in Chinese Acute Myeloid Leukemia Patients by a Validated UPLC-MS/MS Method

Xi Yang; Chen Mei; Xiaoying He; Lingjuan He; Xiaoyang Lu; Hongyan Tong; Yan Lou

doi:10.3390/molecules27051607

Molecules (Feb 2022)

Quantification of Venetoclax for Therapeutic Drug Monitoring in Chinese Acute Myeloid Leukemia Patients by a Validated UPLC-MS/MS Method

Xi Yang,
Chen Mei,
Xiaoying He,
Lingjuan He,
Xiaoyang Lu,
Hongyan Tong,
Yan Lou

Affiliations

Xi Yang: Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, Department of Clinical Phamacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou 310000, China
Chen Mei: Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou 310000, China
Xiaoying He: Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, Department of Clinical Phamacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou 310000, China
Lingjuan He: Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, Department of Clinical Phamacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou 310000, China
Xiaoyang Lu: Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, Department of Clinical Phamacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou 310000, China
Hongyan Tong: Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou 310000, China
Yan Lou: Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, Department of Clinical Phamacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou 310000, China

DOI: https://doi.org/10.3390/molecules27051607
Journal volume & issue: Vol. 27, no. 5
p. 1607

Abstract

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Venetoclax has emerged as a breakthrough for treatment of leukemia with a wide interindividual variability in pharmacokinetics. Herein, a rapid, sensitive, and reliable UPLC-MS/MS method for quantification of venetoclax in plasma was developed and validated. The method was operated in the multiple-reaction monitoring (MRM) mode to detect venetoclax at m/z transition 868.5 > 321.0 and IS at 875.5 > 321.0, respectively. Protein precipitation prior to injection into the LC-MS/MS and the analyte was separated on an ACQUITY UPLC BEH C18 column by gradient elution with acetonitrile and 0.1% formic acid in water. Linear calibration curves were obtained in the range of 25–8000 ng/mL. The specificity, recovery, matrix effect, and stability also met the acceptance criteria of FDA guidance. The method was successfully applied to analyze plasma in acute myeloid leukemia (AML) patients. The peak plasma concentration (Cmax) of venetoclax in Chinese AML patient was 2966.0 ± 1595.0 ng/mL while the trough concentration (Cmin) was 1018.0 ± 729.4 ng/mL. Additionally, Cmax and Cmin showed a positive correlation with AST levels. Furthermore, Cmax was significantly higher in the older patients. The present method can be applied for TDM of venetoclax in treatment of hematological cancers.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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