Tags

Type your tag names separated by a space and hit enter

An LC-MS/MS method for quantification of AC0010, a novel mutant-selective epidermal growth factor receptor (EGFR) inhibitor, and its metabolites in human plasma and the application to a pharmacokinetic study.
J Pharm Biomed Anal 2017; 141:9-18JP

Abstract

AC0010 is an irreversible, mutant-selective EGFR inhibitor that effectively inhibits EGFR active and T790M resistance mutations in non-small cell lung cancer (NSCLC). A sensitive ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was developed and fully validated for determining AC0010 and its metabolites in human plasma. The samples were purified by solid-phase extraction (SPE) columns and separated on a BEH C18 column. Electrospray ionization (ESI) in positive ion mode and multiple reaction monitoring (MRM) were used to monitor the ion transitions of AC0010 (m/z 488→257) and its metabolites M1 (m/z 474→403), M2 (m/z 504→487), M4 (m/z 434→377), M7 (m/z 490→405), MII-1 (m/z 651→434) and MII-2 (m/z 609→434). The results revealed that the method had excellent selectivity and linearity. Intra-day and inter-day precisions (in terms of relative standard deviation, RSD) were lower than 14.4% and the accuracies (in terms of relative error, RE) were within the range of ±10.3% for all the analytes. The lower limit of quantification (LLOQ), stability, matrix effect and extraction recovery were also validated and satisfied the criteria of validation. Finally, the method was successfully applied to a pharmacokinetic study of NSCLC patients after a single oral dose of 350mg of AC0010.

Authors+Show Affiliations

Peking Union Medical College Hospital, N°41 Damucang, Xidan, Xicheng District, Beijing 100032, PR China.Peking Union Medical College Hospital, N°41 Damucang, Xidan, Xicheng District, Beijing 100032, PR China.Peking Union Medical College Hospital, N°41 Damucang, Xidan, Xicheng District, Beijing 100032, PR China.Peking Union Medical College Hospital, N°41 Damucang, Xidan, Xicheng District, Beijing 100032, PR China.Peking Union Medical College Hospital, N°41 Damucang, Xidan, Xicheng District, Beijing 100032, PR China. Electronic address: 13601169983@139.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28414972

Citation

Wang, Lu, et al. "An LC-MS/MS Method for Quantification of AC0010, a Novel Mutant-selective Epidermal Growth Factor Receptor (EGFR) Inhibitor, and Its Metabolites in Human Plasma and the Application to a Pharmacokinetic Study." Journal of Pharmaceutical and Biomedical Analysis, vol. 141, 2017, pp. 9-18.
Wang L, Zheng X, Wang W, et al. An LC-MS/MS method for quantification of AC0010, a novel mutant-selective epidermal growth factor receptor (EGFR) inhibitor, and its metabolites in human plasma and the application to a pharmacokinetic study. J Pharm Biomed Anal. 2017;141:9-18.
Wang, L., Zheng, X., Wang, W., Hu, P., & Jiang, J. (2017). An LC-MS/MS method for quantification of AC0010, a novel mutant-selective epidermal growth factor receptor (EGFR) inhibitor, and its metabolites in human plasma and the application to a pharmacokinetic study. Journal of Pharmaceutical and Biomedical Analysis, 141, pp. 9-18. doi:10.1016/j.jpba.2017.03.051.
Wang L, et al. An LC-MS/MS Method for Quantification of AC0010, a Novel Mutant-selective Epidermal Growth Factor Receptor (EGFR) Inhibitor, and Its Metabolites in Human Plasma and the Application to a Pharmacokinetic Study. J Pharm Biomed Anal. 2017 Jul 15;141:9-18. PubMed PMID: 28414972.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An LC-MS/MS method for quantification of AC0010, a novel mutant-selective epidermal growth factor receptor (EGFR) inhibitor, and its metabolites in human plasma and the application to a pharmacokinetic study. AU - Wang,Lu, AU - Zheng,Xin, AU - Wang,Weicong, AU - Hu,Pei, AU - Jiang,Ji, Y1 - 2017/03/28/ PY - 2016/12/07/received PY - 2017/03/22/revised PY - 2017/03/24/accepted PY - 2017/4/18/pubmed PY - 2018/1/26/medline PY - 2017/4/18/entrez KW - AC0010 KW - EGFR TKI KW - LC–MS/MS KW - Method validation KW - Non-small-cell lung cancer KW - Pharmacokinetics SP - 9 EP - 18 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 141 N2 - AC0010 is an irreversible, mutant-selective EGFR inhibitor that effectively inhibits EGFR active and T790M resistance mutations in non-small cell lung cancer (NSCLC). A sensitive ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was developed and fully validated for determining AC0010 and its metabolites in human plasma. The samples were purified by solid-phase extraction (SPE) columns and separated on a BEH C18 column. Electrospray ionization (ESI) in positive ion mode and multiple reaction monitoring (MRM) were used to monitor the ion transitions of AC0010 (m/z 488→257) and its metabolites M1 (m/z 474→403), M2 (m/z 504→487), M4 (m/z 434→377), M7 (m/z 490→405), MII-1 (m/z 651→434) and MII-2 (m/z 609→434). The results revealed that the method had excellent selectivity and linearity. Intra-day and inter-day precisions (in terms of relative standard deviation, RSD) were lower than 14.4% and the accuracies (in terms of relative error, RE) were within the range of ±10.3% for all the analytes. The lower limit of quantification (LLOQ), stability, matrix effect and extraction recovery were also validated and satisfied the criteria of validation. Finally, the method was successfully applied to a pharmacokinetic study of NSCLC patients after a single oral dose of 350mg of AC0010. SN - 1873-264X UR - https://www.unboundmedicine.com/medline/citation/28414972/An_LC_MS/MS_method_for_quantification_of_AC0010_a_novel_mutant_selective_epidermal_growth_factor_receptor__EGFR__inhibitor_and_its_metabolites_in_human_plasma_and_the_application_to_a_pharmacokinetic_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0731-7085(16)31317-6 DB - PRIME DP - Unbound Medicine ER -