title: Simultaneous determination of clebopride and a major metabolite N-desbenzylclebopride in plasma by capillary gas chromatography-negative-ion chemical ionization mass spectrometry.
abstract: A procedure for the simultaneous assay of clebopride and its major metabolite N-desbenzylclebopride in plasma has been developed. The method utilizes capillary gas chromatography-negative-ion chemical ionization mass spectrometry with selected-ion monitoring of characteristic ions. Employing 2-ethoxy analogues as internal standards, the benzamides were extracted from basified plasma using dichloromethane. Subsequent reaction with heptafluorobutyric anhydride produced volatile mono- and diheptafluorobutyryl derivatives of clebopride and N-desbenzylclebopride, respectively. The methane negative-ion mass spectra of these derivatives exhibited intense high-mass ions ideal for specific quantitation of low levels in biological fluids. Using this procedure the recovery of the drug and metabolite from human plasma was found to be 84.4 +/- 1.5% (n = 3) and 77.4 +/- 4.7% (n = 3), respectively, at 0.5 ng/ml. Measurement of both compounds down to 0.10 ng/ml with a coefficient of variation of less than 10.5% is described. Plasma levels are reported in four volunteers up to 24 h following oral administration of 1 mg of clebopride malate salt.
authors.affiliation: Simbec Research Limited, Merthyr Tydfil, Mid Glamorgan, U.K.
authors.forename: P R
authors.initials: PR
authors.lastname: Robinson
authors.forename: M D
authors.initials: MD
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Maddock
authors.forename: L W
authors.initials: LW
authors.lastname: Rees
mesh_terms: D001549:Benzamides / Q000097:blood* / Q000493:pharmacokinetics; D004355:Drug Stability; D005466:Fluorocarbons; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006207:Half-Life; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008297:Male
chemical_list: D001549:Benzamides; D005466:Fluorocarbons; D007202:Indicators and Reagents; C007924:heptafluorobutyric anhydride; C027676:desbenzylclebopride; C014417:clebopride