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Development of an LC-MS/MS method for quantifying two main metabolites of abivertinib in human plasma.
Biomed Chromatogr 2019; :e4704BC

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 (SPE) was used to process 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 (10mM ammonium acetate comprised of 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 the mode of multiple reaction monitoring (MRM) and electrospray ionization in positive ion mode. This simultaneous determination method was found to have acceptable precision, accuracy and linearity in 0.5-500 ng/mL range for M7 as well as the 0.5-500 ng/mL range for MII-6, accompanied with a mild matrix effect but high recovery. Further stability assessments indicated that both analytes remained stable throughout the entire experimental process beginning from harvesting whole blood to plasma extracting and analyzing.

Authors+Show Affiliations

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, China.Department of Clinical Trial Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China.Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, China.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.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.Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, China.Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, China.Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31629371

Citation

Zheng, Xin, et al. "Development of an LC-MS/MS Method for Quantifying Two Main Metabolites of Abivertinib in Human Plasma." Biomedical Chromatography : BMC, 2019, pp. e4704.
Zheng X, Wang W, Zhang Y, et al. Development of an LC-MS/MS method for quantifying two main metabolites of abivertinib in human plasma. Biomed Chromatogr. 2019.
Zheng, X., Wang, W., Zhang, Y., Ma, Y., Zhao, H., Gao, H., ... Jiang, J. (2019). Development of an LC-MS/MS method for quantifying two main metabolites of abivertinib in human plasma. Biomedical Chromatography : BMC, pp. e4704. doi:10.1002/bmc.4704.
Zheng X, et al. Development of an LC-MS/MS Method for Quantifying Two Main Metabolites of Abivertinib in Human Plasma. Biomed Chromatogr. 2019 Oct 19;e4704. PubMed PMID: 31629371.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of an LC-MS/MS method for quantifying two main metabolites of abivertinib in human plasma. AU - Zheng,Xin, AU - Wang,Weicong, AU - Zhang,Yanbao, AU - Ma,Yuxiang, AU - Zhao,Hongyun, AU - Gao,Huitao, AU - Hu,Pei, AU - Jiang,Ji, Y1 - 2019/10/19/ PY - 2019/03/27/received PY - 2019/08/12/revised PY - 2019/09/16/accepted PY - 2019/10/20/entrez PY - 2019/10/20/pubmed PY - 2019/10/20/medline KW - Abivertinib KW - Human plasma KW - Pharmacokinetics KW - UPLC-MS/MS KW - metabolites SP - e4704 EP - e4704 JF - Biomedical chromatography : BMC JO - Biomed. Chromatogr. N2 - 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 (SPE) was used to process 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 (10mM ammonium acetate comprised of 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 the mode of multiple reaction monitoring (MRM) and electrospray ionization in positive ion mode. This simultaneous determination method was found to have acceptable precision, accuracy and linearity in 0.5-500 ng/mL range for M7 as well as the 0.5-500 ng/mL range for MII-6, accompanied with a mild matrix effect but high recovery. Further stability assessments indicated that both analytes remained stable throughout the entire experimental process beginning from harvesting whole blood to plasma extracting and analyzing. SN - 1099-0801 UR - https://www.unboundmedicine.com/medline/citation/31629371/Development_of_an_LC-MS/MS_method_for_quantifying_two_main_metabolites_of_abivertinib_in_human_plasma L2 - https://doi.org/10.1002/bmc.4704 DB - PRIME DP - Unbound Medicine ER -