caa a22 4500 44580114X CHVBK 20180317145141.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10337-010-1886-1 doi (NATIONALLICENCE)springer-10.1007/s10337-010-1886-1 Simultaneous LC-MS-MS Determination of HM30181A, [2-(2-{4-[2-(6,7-Dimethoxy-3,4-dihydro-1 H -isoquinolin-2-yl)-ethyl]-phenyl}-2 H -tetrazol-5-yl)-4,5-dimethoxyphenyl]amide, as a new P-Glycoprotein Inhibitor and Its Two Metabolites, M1 and M2, in Human Plasma: Application to a Pharmacokinetic Study [Elektronische Daten] [Young Choi, Seul Oh, Seo-Hyun Yoon, Tae-Eun Kim, Namyi Gu, Eun Kim, Han Kim, Kyung-Sang Yu, In-Jin Jang, Sang-Goo Shin, Joo-Youn Cho] A simultaneous simple, rapid, and sensitive LC-MS-MS method was developed and validated for the determination of HM30181A, [2-(2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-2H-tetrazol-5-yl]-4,5-dimethoxy-phenyl]amide, as a P-glycoprotein inhibitor and its two metabolites, M1 and M2, in human plasma using docetaxel as an internal standard (IS). The analytes were extracted from 200μL of biological sample by liquid-liquid extraction using 1mL of methyl-t-butyl ether. Chromatographic separation was carried on a Luna C8 column at 30°C with mobile phase consisting of distilled water with 0.1% formic acid and acetonitrile (75:25, v/v) at a flow rate of 0.7mLmin−1 for human plasma samples. The method was linear over concentration ranges of 0.5-50, 0.1-10, and 0.1-10ngmL−1 for HM30181A, M1, and M2, respectively, in human plasma. The values of coefficient variation for the assay precision were <12.5, <9.10, and <9.96% for HM30181A, M1, and M2, respectively, in human plasma. The values of accuracy were 93.0-108, 94.7-104%, and 95.7-105% for HM30181A, M1, and M2, respectively, in human plasma. This method is simple, sensitive, and applicable for the pharmacokinetic studies of HM30181A and its metabolites in humans. Springer-Verlag, 2011 Liquid chromatography-tandem mass spectrometry nationallicence Metabolites nationallicence Human plasma nationallicence HM30181A nationallicence Choi Young Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut Oh Seul Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut Yoon Seo-Hyun Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut Kim Tae-Eun Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut Gu Namyi Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut Kim Eun Research Center Hanmi Pharm. Co. Ltd., Hwaseong, Republic of Korea aut Kim Han Research Center Hanmi Pharm. Co. Ltd., Hwaseong, Republic of Korea aut Yu Kyung-Sang Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut Jang In-Jin Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut Shin Sang-Goo Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut Cho Joo-Youn Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut Chromatographia Vieweg Verlag 73/3-4(2011-02-01), 273-280 0009-5893 73:3-4<273 2011 73 10337 https://doi.org/10.1007/s10337-010-1886-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10337-010-1886-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Choi Young Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Oh Seul Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Yoon Seo-Hyun Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Tae-Eun Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Gu Namyi Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Eun Research Center Hanmi Pharm. Co. Ltd., Hwaseong, Republic of Korea aut NATIONALLICENCE 700 1- Kim Han Research Center Hanmi Pharm. Co. Ltd., Hwaseong, Republic of Korea aut NATIONALLICENCE 700 1- Yu Kyung-Sang Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Jang In-Jin Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Shin Sang-Goo Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Cho Joo-Youn Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, 101 Daehangno, Jongno-gu, 110-744, Seoul, Republic of Korea aut NATIONALLICENCE 773 0- Chromatographia Vieweg Verlag 73/3-4(2011-02-01), 273-280 0009-5893 73:3-4<273 2011 73 10337 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer