Page 29 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon

1522_C01.fm Page 16 Tuesday, December 2, 2003 10:05 AM

short analysis time of about 6.5 min, and a small sample volume of 2.0 ml
211
urine. However, LC/MS is the preferred technique for quantification. It has
the further advantage that the pharmacologically active morphine-6-glucu-
ronide can also be monitored.

1.4.1.1.5 Nonopioid Analgesics. Nonopioid analgesics are widely used as
over-the-counter drugs. Patients with chronic pain often misuse these drugs
without control by physicians. Although 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 was reviewed
212
by Kraemer and Maurer. GC/MS was described to be suitable for screening
for, and confirmation of, nonopioid analgesics. 213,214 However, the more
acidic compounds like the NSAIDs, can be better detected in acidic screening
procedures (cf. 1.4.1.2.8).

1.4.1.1.6 Anticonvulsants. Anticonvulsants are usually not abused, but
they relatively often lead to accidental, iatrogenic, or suicidal poisonings.
They may impair the ability to drive a car or to work with machines. For
these reasons a screening procedure for anticonvulsants is necessary. Immu-
noassays are available for drug monitoring of particular drugs in plasma. As
the class of anticonvulsants is chemically heterogeneous, there is no immu-
noassay suitable for screening of the whole class of drugs.
Many papers have been published for quantification of anticonvulsants
by HPLC, LC/MS, or GC/MS, 46,215–217 but there is still only one for screening
218
and identification in urine by GC/MS. Newer anticonvulsants like gaba-
pentin, lamotrigine, oxcarbazepine, or valpromide can also be detected by
this procedure. 32

1.4.1.1.7 Benzodiazepines. Benzodiazepines are used as tranquilizers,
hypnotics, anticonvulsants, or muscle relaxants and belong to the most fre-
quently prescribed drugs. They may impair the ability to drive a car or to
operate machines, and they may lead to addiction or severe poisonings,
especially in combination with alcohol. Therefore, screening for benzodi-
azepines is necessary in clinical, forensic, and occupational toxicology. 39
Immunoassays are available for screening, but they need off- or on-line
cleavage of conjugates to avoid a high percentage of false negatives. Also, for
GC/MS confirmation or screening, cleavage of conjugates is mandatory.
39
Both, enzymatic hydrolysis or acid hydrolysis, are used. The latter cleaves
the benzodiazepines to benzophenone derivatives or analogues, 219–221 which
can sensitively be detected by GC/MS after derivatization, e.g., by AC. How-

© 2004 by CRC Press LLC