title: Quantification of meclizine in human plasma by high performance liquid chromatography-mass spectrometry.
abstract: OBJECTIVE
  Meclizine is an antihistamine and has been widely used for prophylactic treatment of motion sickness. To facilitate its pharmacokinetic study in human subjects, a high performance liquid chromatography-mass spectrometric method employing positive electrospray ionization was developed for the determination of meclizine concentration in human plasma.
  
  
  METHODS
  Meclizine together with the internal standard (flunarizine) was extracted from 0.1 ml of human plasma by protein precipitation using acetonitrile. The chromatography was performed using a Zorbax SB-C18 column (150 × 2.1mm, 5 μm, Agilent) with the mobile phase consisting of acetonitrile and 0.2% formic acid containing 2mM amino acetate. Multiple reaction monitoring was used for quantification. The validation of the method including sensitivity, linearity, reproducibility and stability was examined.
  
  
  RESULTS
  The lower limit of quantification (LLOQ) of the developed assay method for meclizine was 0.5 ng/ml and the linear calibration curve was acquired with R² > 0.99 between 0.5 and 200ng/ml. The intra-day and inter-day variation of the current assay was evaluated with the coefficient of variations (CVs%) within 12.92% at LLOQ and 7.15% for other quality control samples, whereas the mean accuracy ranged from 99.2% to 102.7%. The samples were stable under the storage conditions at least for a month.
  
  
  CONCLUSIONS
  The present method provides a robust, fast and sensitive analytical tool for meclizine in human plasma and has been successfully applied to a clinical pharmacokinetic study in 20 subjects.
authors.affiliation: Center for Advancement of Drug Research and Evaluation, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA. zwang@westernu.edu
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
authors.forename: Shuai
authors.initials: S
authors.lastname: Qian
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Moses S S
authors.initials: MS
authors.lastname: Chow
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005444:Flunarizine / Q000032:analysis; D005561:Formates / Q000737:chemistry; D006801:Humans; D016018:Least-Squares Analysis; D013058:Mass Spectrometry / Q000379:methods*; D008468:Meclizine / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000097:Acetonitriles; D005561:Formates; C030544:formic acid; D008468:Meclizine; D005444:Flunarizine; C032159:acetonitrile