Page 36 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon

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1.4.1.2.8 Nonsteroidal Antiinflammatory Drugs (NSAIDs). Nonopiod
analgesics are among the most commonly consumed over-the-counter prep-
arations all over the world. Besides acetylsalicylic acid, paracetamol, and
pyrazole derivatives, so-called NSAIDs, are used against acute and chronic
pain, inflammation, and fever. Altough NSAIDs are perceived to be safe
drugs, they may lead to severe toxic effects in case of acute overdosage or in
case of chronic abuse. They are also misused in doping of humans and horses.
Therefore, they may be encountered in clinical and forensic toxicological
analysis, as well as in doping control. Analysis of such nonopioid analgesics
has been reviewed by Kraemer and Maurer. 212
NSAIDs are classified in arylacetic acid derivatives like indomethacin or
diclofenac; arylpropionic acid derivatives like ibuprofen, naproxen, or keto-
profen; or oxicames like piroxicam. All these drugs have acidic properties
due to (vinylogous) carboxyl groups. Many of the NSAIDs are chiral drugs
but most often marketed as racemates. It is known that the enantiomers have
different pharmacodynamic and pharmacokinetic properties. The anti-
inflammatory activity of NSAIDs has been shown to be mainly evoked by
323
the S-enantiomers. However, this stereoselectivity of action is not manifest
in vivo, due to the thus-far-unique unidirectional metabolic inversion of the
chiral center from the inactive R(–)-isomers to the active S(+)-antipodes. 324
Nevertheless, series of enantioselective determination procedures have been
325
published and reviewed by Davies and Bhushan and Joshi. Several
326
GC/MS, LC, CE, or TLC procedures have been published in the last years for
screening, confirmation, and/or quantification. Derivatization of NSAIDs
before GC is recommended to improve chromatographic properties and to
avoid thermal decarboxylation in the injection port of the GC. Most often,
ME after extraction is used, 55,214,265,269 but extractive methylation has also been
applied. Silylation as an alternative for ME was studied for 26 NSAIDs. 267,268
69
265
The procedures of Laakkonen et al. and Gaillard allowed simultaneous
36
detection of other acidic drugs like barbiturates. Simultaneous determination
of 14 NSAIDs in plasma has been described using LC/MS. 327
1.4.2 General Screening Procedures for Simultaneous Detection
of Several Drug Classes in Urine by GC/MS

In so-called general unknown cases, comprehensive screening procedures
are needed which cover as many drugs or poisons as possible. Only a few
really comprehensive procedures have been published, mainly for urinalysis.
As already mentioned, analytical quality criteria of the parent compound
are of minor value if the concentrations of the metabolites are much higher
in urine than those of the parent drug and if the metabolites are detected
by the procedure. The procedure should be sufficiently sensitive to detect
therapeutic concentrations at least over a 12 to 24 h period after ingestion.

© 2004 by CRC Press LLC