title: Quantification of cyclizine and norcyclizine in human plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
abstract: A rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed and validated for quantification of cyclizine and its main metabolite norcyclizine in human plasma. Samples were prepared by protein precipitation with acetonitrile and cinnarizine was used as internal standard (recovery >87%). The analytes were eluted from a C8 50 mm×2.0 mm analytical column using a linear gradient of methanol and 0.05% formic acid with a total analysis time of 4 min. Analytes were detected by MS/MS using electrospray ionisation in the positive mode with multiple reactions monitoring (MRM) of the precursor ion/product ion transitions 267.2/167.2 for cyclizine and 253.2/167.2 for norcyclizine. Matrix effects were negligible. Standard curves for cyclizine and norcyclizine were linear (r(2)≥0.996) over the range 2-200 ng/mL, with 2 ng/mL representing the lower limit of quantification. Relative standard deviations were <14% for intra- and inter-day precision and the accuracy was within ±8%. The assay was successfully applied to a clinical study.
authors.affiliation: Clinical Pharmacology Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand. berit.jensen@cdhb.govt.nz
authors.forename: Berit Packert
authors.initials: BP
authors.lastname: Jensen
authors.forename: Jane Winifred Ann
authors.initials: JW
authors.lastname: Vella-Brincat
authors.forename: Evan James
authors.initials: EJ
authors.lastname: Begg
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D002936:Cinnarizine / Q000097:blood / Q000737:chemistry; D002986:Clinical Trials as Topic; D003501:Cyclizine / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002936:Cinnarizine; C029632:norcyclizine; D003501:Cyclizine