Page 30 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon

1522_C01.fm Page 17 Tuesday, December 2, 2003 10:05 AM

ever, some benzodiazepines lead to common benzophenones, so that the
interpretation of the result may be difficult. 32,219 An alternative to this workup
222
is enzymatic hydrolysis, SPE and silylation. The sensitivity of GC/MS pro-
cedures, e.g., for detection of low-dosed benzodiazepines, can be markedly
improved by using the the NICI mode. 20,24 This technique is very suitable for
20
benzodiazepine analysis in blood and alternative matrices if LC/MS is not
available. 24

1.4.1.1.8 Sedative–Hypnotics. Sedative–hypnotic drugs are one of the
largest groups of drugs, and they can be divided into barbiturates, benzodi-
azepines (already separately discussed), zopiclone and zolpidem, diphenhy-
dramine and others, including meprobamate, methaqualone, chloral hydrate,
and clomethiazole. They are widely used for the treatment of insomnia,
anxiety, and convulsive disorders, as well as for anesthetic and preanesthetic
treatment. Because of their central nervous and respiratory depressant effects,
they may cause, alone or in combination with other drugs and/or ethanol,
severe poisoning for which treatment is necessary. Furthermore, they may
impair driving ability and the fitness to work with machines, even after
therapeutic doses. In particular, barbiturates and benzodiazepines may lead
to drug dependence, and they are misused by heroin addicts to ease the
withdrawal symptoms from heroin or to augment the effects of “weak her-
oin.” For all these reasons, sedative–hypnotics may be encountered in clinical
or forensic toxicological analysis.
Use of barbiturates has been markedly decreased in recent years. How-
ever, some of them, like phenobarbital and its precursor primidone, are still
used as anticonvulsants for which drug monitoring is necessary. Thiopental
is widely used as a short-term intravenous anesthetic. Thiopental and its
metabolite pentobarbital are often monitored prior to diagnosis of brain
death. A confirmation or screening and identification can be performed by
GC/MS in the EI, full-scan, or SIM mode. Barbiturates have only weakly
acidic properties and can be detected in screening and confirmation proce-
223
dures for basic and neutral drugs (e.g., after acid hydrolysis, LLE, and AC ),
as well as in corresponding procedures for acidic drugs (e.g., after extractive
methylation ).
68
Zopiclone and zolpidem have been found to interact with the omega-1
receptor subtype belonging to the GABA receptor. They have rapid onset
A
of action and short elimination half-life. Unlike benzodiazepines, they have
weak myorelaxant and anticonvulsant effects. They are more and more pre-
scribed as hypnotics instead of benzodiazepines. Diphenhydramine is clini-
cally used as an antihistaminic, antiemetic, and sedative–hypnotic drug.
Immunoassays for screening for zopiclon, zolpidem or diphenhydramine,
meprobamate, methaqualone, and clomethiazole are not commercially

© 2004 by CRC Press LLC