Page 34 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon

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screening procedure for ACE inhibitors and AT-II blockers has been pub-
lished that allows the detection of therapeutic concentrations of most of the
ACE inhibitors and for the AT blocker valsartan in human urine samples
1
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after extractive methylation. If necessary, the drugs can be quantified in
plasma using GC/MS 270–274 or GC/MS-NICI. 24,270,275
1.4.1.2.2 Anticoagulants of the Hydroxycoumarin Type. Anticoagu-
lants of the 4-hydroxycoumarin type are used as therapeutics or as rodenti-
cides of the so-called first generation. Coumarins of the second generation,
the so-called “superwarfarins,” are very potent rodenticides and therefore
very low-dosed. For the differential diagnosis of unclear coagulopathies,
which may occur after ingestion of therapeutic or rodenticide coumarins,
screening is needed. Several screening procedures published in recent years
are described. The relatively polar coumarin derivatives can be sufficiently
separated by reversed phase chromatography. DADs were applied for screen-
ing of coumarin anticoagulants of the first generation and for indanedione
anticoagulants. 36,276 As coumarins have fluorescent properties, fluorescence
detection was used with at least ten times better sensitivity. 277–280 For deter-
mination of “superwarfarins,” HPLC with fluorescence detection was neces-
280
sary. GC/MS was used for the detection of the 4-hydroxycoumarin
anticoagulants of the first generation and their metabolites in urine after
extractive methylation. Derivatization was essential for sensitive GC/MS
65
detection of these vinylogous carboxylic acids and their metabolites (ani-
line/anilide derivatives or phenols). Only alcoholic hydroxy groups could not
be methylated due to their lower nucleophilicity, but this fact did not mark-
edly influence the sensitivity. If necessary, the identified anticoagulants can
be quantified in plasma by HPLC 276,277 or TLC. 281

1.4.1.2.3 Calcium Channel Blockers of the Dihydropyridine Type.
Calcium channel blockers, formerly named calcium antagonists, cover three
main types: the phenylalkylamines (e.g., verapamil), the benzothiazepines
(e.g., diltiazem), and the dihydropyridines (e.g., nifedipine). They are used
in the treatment of cardiac dysrhythmias, angina, and/or hypertension. In
case of overdose, they may lead to severe cardiovascular disorders like hypo-
tension and shock, possibly resulting in life-threatening situations. For diag-
nosis or, even more important, for differential diagnostic exclusion of
poisoning, a screening procedure is necessary for the detection of these drugs
in urine prior to quantification in plasma. The phenylalkylamines and the
benzothiazepines and their metabolites can be detected within the STA pro-
cedure for basic and neutral compounds. 1,251 The dihydropyridines are
excreted only in minor amounts as parent compounds. 282–296 Most of the
urinary metabolites are acidic compounds, so that they can be detected by

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