DETECTION OF 4-HYDROXYCOUMARIN ANTICOAGULANTS AND THEIR METABOLITES IN URINE AS PART OF A SYSTEMATIC TOXICOLOGICAL ANALYSIS PROCEDURE FOR ACIDIC DRUGS AND POISONS BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY AFTER EXTRACTIVE METHYLATION

A gas chromatography-mass spectrometry (GC-MS) procedure was developed for the detection of 4-hydroxycoumarin anticoagulants and their metab olites in urine as part of a systematic toxicological analysis procedu re for acidic drugs and poisons after extractive methylation. The part of the phase-transfer catalyst remaining in the organic phase was rem oved by solid-phase extraction on a diol phase. The compounds were sep arated by capillary GC and identified by computerized MS in the full s can mode. Using mass chromatography with the ions m/z 291, 294, 295, 3 09, 313, 322, 324, 336, 343 and 354, the possible presence of 4-hydrox ycoumarin anticoagulants and/or their metabolites could be indicated. The identity of positive signals in such mass chromatograms was confir med by comparison of the peaks underlying full mass spectra with the r eference spectra recorded during this study. This method allowed the d etection of therapeutic concentrations of phenprocoumon and warfarin i n human urine samples. In absence of human urine, acenocoumarol, couma chlor, coumatetrayl, pyranocoumarin (cyclocumarol) could be detected o nly in rat urine. (C) 1998 Elsevier Science B.V. All rights reserved.