title: Development of 2D chiral chromatography with accelerator mass spectrometry for quantification of (14)C-labeled R- and S-verapamil in plasma.
abstract: BACKGROUND
  A microdose study was performed where 50 µg R/S-(14)C-verapamil was dosed intravenously to human volunteers. In order to quantify the individual R- and S-enantiomers in human plasma a 2D chiral HPLC method with subsequent analysis by accelerator mass spectrometry was verified.
  
  
  RESULTS
  R/S-verapamil was separated on a C18 column and the isolated fraction was applied to a chiral column where the verapamil enantiomers were separated. Experimental recovery (∼73% [coefficient of variation {CV} = 16%] and 66% [CV = 21%] for R- and S-verapamil, respectively) was accounted for by the use of internal standardization from the fluorescence response of nonlabeled R- and S-verapamil. The precision of the assay ranged from 4.1 to 15.9% CV and the limit of quantitation was 1.95-4.81 pg/ml for R-verapamil and 1.76-3.34 pg/ml for S-verapamil.
  
  
  CONCLUSIONS
  This method was successfully applied to the analysis of R- and S-verapamil in human plasma.
authors.affiliation: Xceleron Ltd, York, YO10 5NY, UK.
authors.forename: M
authors.initials: M
authors.lastname: Simpson
authors.forename: G
authors.initials: G
authors.lastname: Lappin
authors.forename: B J
authors.initials: BJ
authors.lastname: Keely
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods*; D002250:Carbon Radioisotopes / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D013237:Stereoisomerism; D014700:Verapamil / Q000097:blood* / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D002250:Carbon Radioisotopes; D014700:Verapamil