caa a22 4500 445313633 CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-011-0423-8 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0423-8 Clinical Relevance of Liquid Chromatography Tandem Mass Spectrometry as an Analytical Method in Microdose Clinical Studies [Elektronische Daten] [Naoe Yamane, Zenzaburo Tozuka, Makiko Kusama, Kazuya Maeda, Toshihiko Ikeda, Yuichi Sugiyama] ABSTRACT: Purpose: To investigate the potency of LC-MS/MS by means of sensitivity and the applicability for cassette dosing in microdose clinical trials. Methods: Thirty one top-selling 31 drugs were spiked to human plasma, extracted, and analyzed by LC-MS/MS. Results: The lower limits of quantification for each drug varied from 0.08 to 50pg/mL, and were lower than one eighth of the assumed maximum plasma concentration at microdose in all drugs except for losartan, indicating the high performance in acquisition of full pharmacokinetic profiles at microdose. We also succeeded in simultaneous analysis of multiple compounds, assuming a situation of cassette dosing in which multiple drug candidates would be administrated simultaneously. Conclusions: Together with the features of LC-MS/MS, such as immediate verification, the utilization of non-radiolabeled drugs and no special facilities, we suppose that LC-MS/MS analysis would be widely applicable in conducting microdose clinical studies. Springer Science+Business Media, LLC, 2011 cassette dosing nationallicence exploratory clinical trials nationallicence LC-MS/MS nationallicence lower limit of quantification nationallicence microdose study nationallicence AMS : accelerator mass spectrometry nationallicence CmaxClin : Cmax in clinical PK study nationallicence CmaxMD : Cmax in microdose study nationallicence CV : coefficient of variation nationallicence DoseClin : dose in clinical PK study nationallicence DoseMD : dose in microdose study nationallicence EMEA : European Agency for the Evaluation of Medicinal Products nationallicence EUMAPP : European Union Microdose AMS Partnership Programme nationallicence FDA : Food and Drug Administration nationallicence HILIC : hydrophilic interaction chromatography nationallicence IS : internal standard nationallicence LC-MS/MS : liquid chromatography-tandem mass spectrometry nationallicence LLE : liquid-liquid extraction nationallicence LLOQ : lower limit of quantification nationallicence MHLW : Ministry of Health Labour and Welfare nationallicence MRM : multiple reaction monitoring nationallicence ODS : octadecylsilyl nationallicence PET : positron emission tomography nationallicence PK : pharmacokinetic nationallicence QC : quality control nationallicence RE : relative error nationallicence SPE : solid-phase extraction nationallicence Yamane Naoe Graduate School of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Hongo, Bunkyo-ku, Japan aut Tozuka Zenzaburo Sekisui Medical Co., Ltd., 319-1182, Muramatsu, Tokai, Japan aut Kusama Makiko Graduate School of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Hongo, Bunkyo-ku, Japan aut Maeda Kazuya Graduate School of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Hongo, Bunkyo-ku, Japan aut Ikeda Toshihiko Yokohama College of Pharmacy, 245-0066, Yokohama, Kanagawa, Japan aut Sugiyama Yuichi Graduate School of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Hongo, Bunkyo-ku, Japan aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1963-1972 0724-8741 28:8<1963 2011 28 11095 https://doi.org/10.1007/s11095-011-0423-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0423-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamane Naoe Graduate School of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Hongo, Bunkyo-ku, Japan aut NATIONALLICENCE 700 1- Tozuka Zenzaburo Sekisui Medical Co., Ltd., 319-1182, Muramatsu, Tokai, Japan aut NATIONALLICENCE 700 1- Kusama Makiko Graduate School of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Hongo, Bunkyo-ku, Japan aut NATIONALLICENCE 700 1- Maeda Kazuya Graduate School of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Hongo, Bunkyo-ku, Japan aut NATIONALLICENCE 700 1- Ikeda Toshihiko Yokohama College of Pharmacy, 245-0066, Yokohama, Kanagawa, Japan aut NATIONALLICENCE 700 1- Sugiyama Yuichi Graduate School of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Hongo, Bunkyo-ku, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1963-1972 0724-8741 28:8<1963 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer