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 β-glucuronidase to cleave the glucuronide conjugates of both compounds pri...

Full description

Saved in:
Bibliographic Details
Published in:Journal of chromatography. B, Biomedical applications Biomedical applications, 1996-07, Vol.682 (2), p.273-281
Main Authors: Tulich, Linda J., Randall, Jared L., Kelm, Gary R., Wehmeyer, Kenneth R.
Format: Article
Language:English
Subjects:
Chromatography, High Pressure Liquid
Desmethylmebeverine alcohol
Gas Chromatography-Mass Spectrometry - methods
Glucuronidase - metabolism
Humans
Isotopes
Mebeverine
Mebeverine alcohol
Parasympatholytics - pharmacokinetics
Phenethylamines - blood
Phenethylamines - pharmacokinetics
Reproducibility of Results
Sensitivity and Specificity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 β-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.
ISSN:0378-4347
1572-6495
DOI:10.1016/0378-4347(96)00039-4