title: The enantioselective determination of chlorpheniramine and its major metabolites in human plasma using chiral chromatography on a beta-cyclodextrin chiral stationary phase and mass spectrometric detection.
abstract: A sensitive enantioselective high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of plasma concentrations of (-)(R)- and (+)(S)-chlorpheniramine (CP) and their metabolites, desmethyl-chlorpheniramine (DCP), didesmethyl-chorpheniramine (DDCP) and chlorpheniramine N-oxide (CPNO). Enantioselective separations were achieved on a beta-cyclodextrin chiral stationary phase (CYCLOBOND I 2000) with a mobile phase consisting of diethylamine acetate (0.25%, pH 4.4):methanol:acetonitrile [85:7.5:7.5, (v/v/v)]and a flow-rate of 0.5 ml/min. For CP, the enantioselectivity (alpha) of the separation was 1.12 with a resolution factor (R(s)) of 1.17. The method was validated for CP by using mass spectroscopy detection (MSD). Concentrations of each enantiomer could be measured down to 125 pg/ml from a 1-ml plasma sample. Extracted calibration curves were linear from 0.13 to 50.00 ng/ml for each enantiomer. The method was applied to samples from two clinical studies.
authors.affiliation: Bioanalytical Center, Georgetown University Clinical Research Center, Washington, DC, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Fried
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Young
authors.forename: Sally
authors.initials: S
authors.lastname: Usdin Yasuda
authors.forename: Irving W
authors.initials: IW
authors.lastname: Wainer
mesh_terms: D000328:Adult; D018926:Anti-Allergic Agents / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D002744:Chlorpheniramine / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D002845:Chromatography / Q000379:methods; D018592:Cross-Over Studies; D003505:Cyclodextrins / Q000737:chemistry*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D013237:Stereoisomerism; D047392:beta-Cyclodextrins
chemical_list: D018926:Anti-Allergic Agents; D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D002744:Chlorpheniramine; C031215:betadex