Biomedical Engineering Reference
In-Depth Information
developed in several illnesses such as chronic pain, fibromyalgia, irritable bowel
syndrome, or chronic fatigue syndrome.
Due to their high prescription, these therapeutic drugs are easy to acquire by
depressed patients, who are prone to suicide attempts. This explains why antide-
pressants are among the most frequent therapeutic drug classes involved in forensic
and clinical intoxications, mainly associated to voluntary intoxications [
1-
4
] .
Antidepressants with sedative side effects, like TCAs, could also be potentially used
in drug facilitated sexual assault (DFSA) crimes [
5
] . Therefore, analytical tech-
niques for the reliable identification and quantification of antidepressants should be
available in clinical and forensic toxicology laboratories in order to perform a com-
petent toxicological report. In addition, some antidepressants impair cognitive and
psychomotor functions, and may increase the risk of driving accidents when under
their in fl uence [
6-
8
]. For this reason, the Guidelines for Research in Drugged
Driving elaborated by international experts in order to harmonize research in this
field recommended the inclusion of sedative antidepressants in the panel of drugs to
be analyzed in specimens collected from the roadside [
9
]. In addition to toxicologi-
cal applications, analytical methodologies are also required to monitor plasmatic
concentrations of some antidepressants. Therapeutic drug monitoring (TDM) of
TCA is widely accepted [
10-
13
] because of their narrow therapeutic window, and
the development of severe cardiotoxicity and CNS toxicity close to the upper thera-
peutic concentrations; moreover, the enzymes involved in their metabolization show
genetic polymorphism, being in part responsible for the interindividual variability
in the plasmatic concentrations achieved at a given dose. Although new generations
of antidepressants are less toxic and have wider therapeutic ranges due to a more
selective mechanism of action, TDM of their plasmatic levels could be justified in
special situations (assess compliance in nonresponder patients, hepatic or renal
impairment, polymedicated patients, poor metabolizers, etc.) [
11-
13
] . Antidepressant
determination also is required to perform pharmacokinetic, bioavailability, and
bioequivalence studies.
Different immunoassays are commercialized for the analysis of some antide-
pressants [
14-
17
]. Although useful for fast identification of these analytes, these
techniques have several limitations: TCA are the main targeted analytes, it is not
possible to differentiate between structurally related antidepressants, and several
substances can cross-react with antidepressant assays [
18-
20
] . Therefore, positive
results must be confirmed with more specific techniques, usually using chromatog-
raphy based procedures coupled to different detectors. Mass spectrometry is one of
the most common detectors employed in clinical and toxicological analysis because
of its high selectivity and sensitivity. Gas chromatography coupled to mass spec-
trometry (GC-MS) is a robust and well-established technique, and it is considered
the golden standard for general unknown screening. Several GC-MS analytical
methodologies have been described for identification and quantification of
antidepressants in different biological matrices [
21-
25
]; however, in most cases,
antidepressants have to be derivatized because of their relatively high polarity. In
the 1990s, the development of atmospheric pressure ionization interfaces (API)
allowed the successful hyphenation of liquid chromatography to mass spectrometry
