Determination of two mebeverine metabolites, mebeverine alcohol and desmethylmebeverine alcohol, in human plasma by a dual stable isotope-based gas chromatographic-mass spectrometric method.
A dual stable isotope-based GC-MS method was developed for the simultaneous determination of two metabolites of mebeverine, mebeverine alcohol and desmethylmebeverine alcohol, in human plasma. Plasma samples were treated with beta-glucuronidase to cleave the glucuronide conjugates of both compounds prior to analysis. The treated plasma was prepared for analysis by solid-phase extraction using octadecylsilane cartridges. The isolated metabolites were derivatized and analyzed by GC-MS using selected-ion monitoring. Plots of peak-area ratio were linear with metabolite concentration from 2 to 200 ng/ml and the limit of detection for both metabolites was 0.5 ng/ml. The GC-MS methodology was applied to the analysis of plasma from human subjects following peroral administration of mebeverine. Pharmacokinetic parameters for both metabolites were determined and suggest that relative systemic mebeverine exposure may potentially be assessed using metabolite kinetics, if the latter subsequently are demonstrated to be linear with mebeverine dose.
Tulich
L J
LJ
Procter & Gamble Pharmaceuticals, Cincinnati, OH 45253, USA.
Randall
J L
JL
Kelm
G R
GR
Wehmeyer
K R
KR
D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007554:Isotopes; D010276:Parasympatholytics / Q000493:pharmacokinetics*; D010627:Phenethylamines / Q000097:blood* / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D007554:Isotopes; D010276:Parasympatholytics; D010627:Phenethylamines; C076513:mebeverine alcohol; C103423:desmethylmebeverine alcohol; C005096:mebeverine; D005966:Glucuronidase