title: Determination of mesoridazine by liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic study in rats.
abstract: The object of the present study was to develop and validate an assay method of mesoridazine in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma samples from rats were prepared by simple protein precipitation and injected onto the LC-MS/MS system for quantification. Mesoridazine and chlorpromazine as an internal standard (IS) were separated by a reversed phase C18 column. A mobile phase was composed of 10mM ammonium formate in water and acetonitrile (ACN) (v/v) by a linear gradient system, increasing the percentage of ACN from 2% at 0.4min to 98% at 2.5min with 4min total run time. The ion transitions monitored in positive-ion mode [M+H](+) of multiple-reaction monitoring (MRM) were m/z 387>126 for mesoridazine and m/z 319>86 for IS. The detector response was specific and linear for mesoridazine at concentrations within the range 0.001-4μg/ml and the correlation coefficient (R(2)) was greater than 0.999 and the signal-to-noise ratios for the samples were ≥10. The intra- and inter-day precision and accuracy of the method were determined to be within the acceptance criteria for assay validation guidelines. The matrix effects were approximately 101 and 99.5% from rat plasma for mesoridazine and chlorpromazine, respectively. Mesoridazine was stable under various processing and/or handling conditions. Mesoridazine concentrations were readily measured in rat plasma samples after intravenous and oral administration. This assay method can be practically useful to the pharmacokinetic and/or toxicokinetic studies of mesoridazine.
authors.affiliation: Department of Drug Discovery Platform Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea; College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Im
authors.affiliation: Department of Drug Discovery Platform Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
authors.forename: Myoung Joo
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Department of Drug Discovery Platform Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Seo
authors.affiliation: Department of Drug Discovery Platform Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
authors.forename: Sung Heum
authors.initials: SH
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Drug Discovery Platform Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea. Electronic address: ahns@krict.re.kr.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood*; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods*; D008297:Male; D008653:Mesoridazine / Q000097:blood*; D051381:Rats / Q000097:blood*; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods
chemical_list: D014150:Antipsychotic Agents; D008653:Mesoridazine
keywords: LC–MS/MS; Mesoridazine; Method validation; Pharmacokinetics; Rat plasma; Toxicokinetics