SCREENING FOR THE DETECTION OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS, THEIR METABOLITES, AND AT-II RECEPTOR ANTAGONISTS

A gas chromatography-mass spectrometry (GC-MS) screening procedure was developed for the detection of angiotensin-converting enzyme (ACE) in hibitors; their metabolites, and angiotensin (AT) II receptor antagoni sts in urine as part of a systematic toxicologic analysis procedure fo r acidic drugs and poisons after extractive methylation. The part of t he phase-transfer catalyst remaining in the organic phase was removed by solid phase extraction on a diol phase. The compounds were separate d by capillary GC and identified by computerized MS in the full scan m ode. Using mass chromatography with the ions m/z 157, 160, 172, 192, 2 04, 220, 234, 248, 249, and 262, the possible presence of ACE inhibito rs, their metabolites, and AT II antagonists could be indicated. The i dentity of positive signals in such mass chromatograms was confirmed b y comparison of the peaks underlying full mass spectra with the refere nce spectra recorded during this study,This method allowed detection o f therapeutic concentrations of ACE inhibitors (benazepril, enalapril, perindopril, quinapril, ramipril, trandolapril, their metabolites, or both) and therapeutic concentrations of the AT II antagonist, valsart an, in human urine samples. Human urine samples were not available for testing cilazapril, moexipril, and losartan; they were detected only in rat urine. The overall recoveries of ACE inhibitors ranged between 80% and 88%, with a coefficient of variation (CV) of less than 10% and the limit of detection of at least 10 ng/ml (signal to noise ratio 3) in the full-scan mode. The overall recovery of the valsartan was 68%, with a CV of less than 10%; the limit of detection was at least 10 ng /ml (S/N 3) in the full scan mode.