title: Determination of tolperisone in human plasma by liquid chromatography/tandem mass spectrometry for clinical application.
abstract: We have developed and validated a simple, rapid, and sensitive liquid chromatography analytical method employing tandem mass spectrometry (LC-MS/MS) for the determination of tolperisone, a centrally acting muscle relaxant, in human plasma. After liquid-liquid extraction with methyl t-butyl ether, chromatographic separation of tolperisone was performed using a reversed-phase Luna C(18) column (2.0mm×50mm, 5μm particles) with a mobile phase of 10mM ammonium formate buffer (pH 3.5) - methanol (12:88, v/v) and quantified by tandem mass detection in ESI positive ion mode. The flow rate of the mobile phase was 250μL/min and the retention times of tolperisone and the internal standard (IS, dibucaine) were both 0.6min. The calibration curves were linear over a range of 0.5-300ng/mL (r>0.999). The lower limit of quantification, using 200μL human plasma, was 0.5ng/mL. The mean accuracy and precision for intra- and inter-day validation of tolperisone were within acceptable limits. The LC-MS/MS method reported here showed improved sensitivity for quantification of tolperisone in human plasma compared with previously described analytical methods. Lastly, the validated method was successfully applied to a pharmacokinetic study in humans.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Chang-Ik
authors.initials: CI
authors.lastname: Choi
authors.forename: Jung-In
authors.initials: JI
authors.lastname: Park
authors.forename: Hye-In
authors.initials: HI
authors.lastname: Lee
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Bae
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014049:Tolperisone / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D014049:Tolperisone