title: Simultaneous determination of clevidipine and its primary metabolite in dog plasma by liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic study.
abstract: A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of clevidipine and its primary metabolite H152/81 in dog plasma after protein precipitation with acetonitrile using felodipine as the internal standard (IS). Chromatographic separation was performed on a XB C18 column (2.1mm×50mm, 3.5μm) under isocratic conditions with the mobile phase consisting of acetonitrile and 20mM ammonium acetate buffer (pH 7.0) (40:60, v/v) at the flow rate of 0.3ml/min. The run time was 5.5min. Mass spectrometric analysis was performed on a triple quadrupole mass spectrometer operated in the multiple reaction monitoring (MRM) mode with the transitions of m/z 473.0→338.2 for clevidipine, m/z 356.1→324.0 for H152/81 and m/z 383.9→338.2 for the IS. The method was fully validated in terms of selectivity, linearity, lower limit of quantification (LLOQ), accuracy, precision, stability, matrix effect and recovery over a concentration range of 0.15-200ng/ml for clevidipine and 10-2000ng/ml for H152/81, respectively. The analytical method was applied to support a pharmacokinetic study of simultaneous determination of clevidipine and H152/81 in ten healthy beagle dogs.
authors.affiliation: Institute of Clinic Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Clinic Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Huqun
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Clinic Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: He
authors.affiliation: Institute of Clinic Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Jia
authors.affiliation: Institute of Clinic Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Institute of Clinic Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Xu
authors.affiliation: Institute of Clinic Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: shining_119@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Clinic Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: wenzhang_sci@163.com.
authors.forename: Weiyong
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D001711:Biotransformation; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D004095:Dihydropyridines / Q000097:blood* / Q000493:pharmacokinetics*; D004285:Dogs; D007262:Infusions, Intravenous; D057230:Limit of Detection; D016014:Linear Models; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D000959:Antihypertensive Agents; D004095:Dihydropyridines; D011725:Pyridines; C511533:monomethyl 4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-2,5-dicarboxylate; C118563:clevidipine
keywords: Clevidipine; Liquid chromatography tandem mass spectrometry; Metabolite; Pharmacokinetic