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performed before extensive diagnostic work is started. Laxative use is
common among adolescents with anorexia nervosa, and the risk of associ-
253
ated medical complications increases over time. GC/MS procedures have
been described for this purpose. 1,254,255 For the detection of the anthraqui-
none glycosides, which cannot easily be analyzed by GC/MS, high-perform-
ance thin-layer chromatographic (HPTLC) methods 256,257 as well as HPLC-
DAD methods have been developed. 258
1.4.1.2 Screening Procedures for Detection of Particular
Drug Classes of Acidic Drugs and/or Their
Metabolites in Urine
Some classes of acidic drugs, or drugs which are metabolized to acidic com-
pounds like the cardiovascular drugs ACE inhibitors and AT-II blockers,
dihydropyridine calcium channel blockers, diuretics, coumarin anticoagu-
lants, antidiabetics of the sulfonylurea type, barbiturates, or NSAIDs, are
relevant to clinical and forensic toxicology or doping. Therefore, these acidic
drugs should also be monitored, ideally in one procedure.
For STA of acidic drugs and/or their metabolites, gas chromatographic
procedures (GC with MS or other detectors), liquid chromatographic proce-
dures (LC with DAD or other detectors), thin-layer chromatographic (TLC
with different detection modes) or capillary electrophoretic (CE) procedures
16
have been used. As in STA, a broad range of unknown compounds — even
in unknown combinations — must be screened, differentiated, and identified;
the separation must be as powerful and universal as possible, and the detection
modes must be of the highest specificity and universality. In most papers, the
GC/MS coupling was applied. 9,36,55,65–67,72,214,259–269 As acidic compounds are too
polar for sensitive GC separation, derivatization by alkylation or silylation is
required. Extractive alkylation has proved to be a powerful procedure for
simultaneous extraction and derivatization of many acidic compounds. 16,65–69,84
1.4.1.2.1 ACE Inhibitors and Angiotensin II AT Receptor Blockers.
1
ACE inhibitors are widely used in the treatment of hypertension and con-
gestive heart failure. AT blockers, a new drug class, are used for the same
1
indication. In case of poisoning, ACE inhibitors or AT blockers may lead to
1
severe cardiovascular disorders like hypotension and shock. For diagnosis or
for differential diagnostic exclusion of such poisoning, a screening procedure
is necessary for the detection of these drugs in urine. ACE inhibitors have a
free carboxylic acid group. A further carboxylic group is formed by hydrolysis
of the ethyl esters during metabolism and/or sample preparation. The phar-
macologically active dicarboxylic acids, the so-called “prilates,” are used for
parenteral application. AT blockers have also acidic properties, resulting
1
from a carboxylic acid function and/or from the tetrazole ring. Only one
© 2004 by CRC Press LLC