caa a22 4500 445801395 CHVBK 20180317145142.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s10337-010-1839-8 doi (NATIONALLICENCE)springer-10.1007/s10337-010-1839-8 Determination of Mildronate in Human Plasma and Urine by UPLC-Positive Ion Electrospray Tandem Mass Spectrometry [Elektronische Daten] [Li-Jing Cai, Jun Zhang, Wen-Xing Peng, Rong-Hua Zhu, Jian Yang, Gang Cheng, Xiu-Mei Wang] A simple, rapid, and selective method to determine the concentration of mildronate in human plasma and urine using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) was developed and validated. The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring mode via electrospray ionization at m/z 147.2-58.0 for mildronate and m/z 147.2-87.8 for the internal standard, carbachol. The UPLC separation was carried out with a UPLC BEH HILIC column. The mobile phase consisted of 0.08% formic acid in 30mM ammonium acetate solution and acetonitrile (23:77, v/v). Plasma samples were extracted from plasma by protein precipitation and urine samples were diluted with the mobile phase. The analysis time was 3.5min for each sample. Linear calibration curves ranged from 0.10 to 100.00μgmL−1 in human plasma and 0.50 to 600.00μgmL−1 in urine. The method had been successfully applied to a pharmacokinetic study in healthy volunteers. After single intravenously administration of 250, 500, and 750mg mildronate, the elimination half-life (t 1/2) were (2.74±0.67), (4.86±0.82) and (5.16±0.77) h, respectively. The t 1/2 for the 250mg dose did vary significantly with other dosages (P<0.05), mildronate may have non-linear pharmacokinetics in humans. Springer-Verlag, 2011 Ultra performance liquid chromatography nationallicence UPLC-MS-MS nationallicence Pharmacokinetic study nationallicence Mildronate nationallicence Cai Li-Jing Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut Zhang Jun Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut Peng Wen-Xing Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut Zhu Rong-Hua Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut Yang Jian Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut Cheng Gang Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut Wang Xiu-Mei Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut Chromatographia Vieweg Verlag 73/7-8(2011-04-01), 659-665 0009-5893 73:7-8<659 2011 73 10337 https://doi.org/10.1007/s10337-010-1839-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10337-010-1839-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cai Li-Jing Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Jun Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut NATIONALLICENCE 700 1- Peng Wen-Xing Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut NATIONALLICENCE 700 1- Zhu Rong-Hua Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut NATIONALLICENCE 700 1- Yang Jian Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut NATIONALLICENCE 700 1- Cheng Gang Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut NATIONALLICENCE 700 1- Wang Xiu-Mei Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, Central South University, 410011, Changsha, People's Republic of China aut NATIONALLICENCE 773 0- Chromatographia Vieweg Verlag 73/7-8(2011-04-01), 659-665 0009-5893 73:7-8<659 2011 73 10337 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer