Biomedical Engineering Reference
In-Depth Information
Although it is not recommended, the use of commercially available pharmaceuticals
as IS could be only justified if the method is applied to a controlled administration
study in which the presence of that IS in the biological matrix can be ruled out.
Analytical methods for TDM should cover therapeutic ranges, and LLOQ
requirements are not as low as those for pharmacokinetic applications. LC-MS
methodologies for the determination of one specific antidepressant could also be
applied in these cases. However, as previously stated in this chapter, multianalyte
procedures are preferable because they are simpler, faster, cheaper, and allow for the
determination of several analytes using the same sample aliquot. Moreover,
multianalyte procedures are not only useful, but also required in clinical or forensic
applications, where the target antidepressant is initially unknown, and several of
them could be involved in the intoxication.
LC-MS(MS) methods including several antidepressants will be described in
more detail. Some of these methods include analytes belonging to the same
antidepressant group. Alves et al. [
80
] developed an LC-MS method for the deter-
mination of some TCAs in plasma with a total run time of 18 min. Kollroser et al.
described two LC-IT-MS procedures in plasma for the determination of seven
TCAs [
74
] and three SSRIs [
75
], respectively, using an online preparative col-
umn. Total analysis time per sample was 12 and 6 min, respectively. The main
disadvantage of these methods is that a therapeutic drug was used as IS, hindering
its applicability to TDM or clinical and forensic toxicology analysis. Also Juan
et al. [
66
] used fluvoxamine as IS for the determination of several SSRIs; how-
ever, the authors argue that this drug was not commercially available in their
region, and that patients' history was studied in order to exclude fluvoxamine
intake. Breaud et al. [
78
] developed a LC-MS/MS method for two TCAs and their
main metabolites by turbulent flow LC-MS/MS, which allowed analyte determi-
nation from only 10 mL of plasma, with a total analysis time of 3.5 min from the
second injection. Zhang et al. [
58
] used a LC-TOF-MS instrument for accurate
mass measurement of TCAs in 18 s, using reference standards and plasma sam-
ples fortified with these analytes; however, validated linearity ranges were below
the upper therapeutic concentrations and, therefore, evaluation of dilution integ-
rity would be needed in order to analyze specimens from patients on antidepres-
sant treatment or from intoxication cases. More details on validation experiments
performed in these methods are shown in Table
1
.
Other authors described LC-MS or LC-MS/MS methods in serum, plasma or
whole blood for the determination of several analytes belonging to different anti-
depressant groups. LC-MS methods were developed by Halvorsen et al. [
65
] and
Gutteck et al. [
108
] using an ion trap and a single quadrupole mass analyzer,
respectively, with chromatographic elution of the analytes included in each
method within 10 min. Analytes included in Gutteck's et al. method were divided
in four groups depending on their therapeutic ranges, and slightly different
extraction and chromatographic procedures were applied to each group.
Shinozuka et al. [
69
] extended the number of antidepressants using a LC-IT-MS
instrument, and chromatographic separation was performed in 30 min. Tandem
LC-MS/MS instruments were also employed in several occasions [
53,
59,
60,
