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 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.
Walles
Markus
M
Department of Analytical Chemistry, Fraunhofer Institute of Toxicology and Aerosol Research, Drug Research and Clinical Inhalation, Nikolai Fuchs Str. 1, 30625 Hannover, Germany.
Borlak
Jürgen
J
Levsen
Karsten
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008168:Lung / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D009206:Myocardium / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014700:Verapamil / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*
D014700:Verapamil