Application of restricted access material (RAM) with precolumn-switching and matrix solid-phase dispersion (MSPD) to the study of the metabolism and pharmacokinetics of Verapamil

In the pharmaceutical industry, studies of the metabolism and pharmacokinetics of drugs are important routine applications which require the analysis of the precursor drug and its metabolites in various biological matrices, such as plasma, serum, urine, cell culture media and tissue samples. In this...

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Bibliographic Details
Published in:Analytical and bioanalytical chemistry 2002-12, Vol.374 (7-8), p.1179-1186
Main Authors: Walles, Markus, Borlak, Jürgen, Levsen, Karsten
Format: Article
Language:English
Subjects:
Analytical chemistry
Animals
Biological properties
Biological samples
Calcium antagonists
Cell culture
Chromatography, High Pressure Liquid - methods
Culture media
Dispersion
Drug metabolism
Lung - chemistry
Male
Mass Spectrometry
Metabolism
Metabolites
Myocardium - chemistry
Pharmaceutical industry
Pharmaceuticals
Pharmacodynamics
Pharmacokinetics
Pharmacology
Rats
Rats, Sprague-Dawley
Sample preparation
Solid phases
Switching
Time Factors
Tissue culture
Verapamil
Verapamil - analysis
Verapamil - chemistry
Verapamil - metabolism
Verapamil - pharmacokinetics
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Summary:In the pharmaceutical industry, studies of the metabolism and pharmacokinetics of drugs are important routine applications which require the analysis of the precursor drug and its metabolites in various biological matrices, such as plasma, serum, urine, cell culture media and tissue samples. In this study, two new and simple methods of sample preparation were optimized and validated: on the one hand, a column-switching technique with a restricted access material (RAM) was used to analyze biological fluids, and on the other hand, matrix solid-phase dispersion (MSPD) was applied to the extraction of analytes from tissue samples. Identification of the metabolites was done with a LC-MS system (ion trap in the MS(n)mode) coupled both on-line (RAM) and off-line (MSPD). Using the common calcium antagonist Verapamil, it is shown that these two methods allow rapid identification of phase I and phase II metabolites from biological samples and are suitable for pharmacokinetic and pharmacodynamic studies of pharmaceuticals in biological matrices.
ISSN:1618-2642
1618-2650
DOI:10.1007/s00216-002-1614-2