Development of an LC–MS/MS method for quantifying two main metabolites of abivertinib in human plasma |
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Authors: | Xin Zheng Weicong Wang Yanbao Zhang Yuxiang Ma Hongyun Zhao Huitao Gao Pei Hu Ji Jiang |
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Institution: | 1. Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China;2. Clinical Trial Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;3. Department of Medical Oncology, Sun Yatsen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China |
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Abstract: | Abivertinib represents a highly selective irreversible epidermal growth factor receptor tyrosine kinase inhibitor. Two major metabolites of abivertinib, M7 and MII-6, were detected in human plasma, which are recommended to be monitored for safety reasons in clinical trial. A high-throughput quantification method utilizing liquid chromatography–tandem mass spectrometry was designed and verified to quantify abivertinib's primary metabolites in human plasma. Solid-phase extraction was used to process the plasma, and then the analytes underwent a gradient elution separation in an Aquity UPLC BEH C18 column (1.7 μm, 2.1 × 50 mm) with mobile phase A (10 mm ammonium acetate containing 0.1% formic acid) and mobile phase B (methanol–acetonitrile, 2:8, v/v, with 0.1% formic acid). Ion transitions of M7 (m/z 490.2 → 405.1) and MII-6 (m/z 476.2 → 391.1) were monitored under multiple reaction monitoring mode and electrospray ionization in positive ion mode. This simultaneous determination method was found to have acceptable precision, accuracy and linearity in the 0.5–500 ng/mL range for M7 and the 0.5–500 ng/mL range for MII-6, accompanied by a mild matrix effect but high recovery. Further stability assessments indicated that both analytes remained stable throughout the entire experimental process from harvesting whole blood to plasma extraction and analysis. |
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Keywords: | abivertinib human plasma metabolites pharmacokinetics UPLC-MS/MS |
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