Biomedical Engineering Reference
In-Depth Information
72, 77, 109 ] . Kirchherr et al. [ 53 ] employed protein precipitation of 0.1 mL of
serum for the determination of 48 psycotherapeutics, including the most com-
mon antidepressants, with a total chromatographic run of 8 min. Also Remane
et al. [ 59 ] developed a multianalyte procedure for the determination of 136 ana-
lytes from different drug classes using a generic LLE procedure; however, only
matrix effect, recovery, and process efficiency were evaluated for method valida-
tion. Santos-Neto et al. [ 77 ] developed a LC-MS/MS method for the analysis of
some antidepressants in plasma and urine using a monolithic column for simul-
taneous online sample preparation and chromatographic separation, with a total
analysis time of 8 min. Sauvage et al. [ 76 ] extended the number of antidepres-
sants determined in 0.1 mL of serum using turbulent flow LC-MS/MS, and
decreased the total analysis time to 6 min. De Castro et al. [ 72 ] developed an
online SPE-LC-MSMS procedure using 0.05 mL of plasma, where the complete
analytical process for the determination of nine antidepressants was performed
in 20 min. Table 1 shows the parameters evaluated for method validation, as well
as analytes employed as IS, in each of these methods.
Although most LC-MS(MS) methods for antidepressants were applied to
plasma, serum, or whole blood specimens, some analytical methodologies were
also described in other biological matrices. Petsalo et al. [ 45 ] identi fi ed 20 bupro-
pion metabolites in urine by accurate mass measurement using a LC-TOF-MS
instrument. De Santana [ 42 ] applied a LC-MS/MS method with SPME extraction
to urine samples to assess cumulative urinary excretion of mirtazapine and two
metabolites. LC-MS/MS methods were also developed to compare enantiomers
disposition of reboxetine [ 110 ], and bupropion and its metabolite [ 43 ] in plasma
and urine specimens. Bupropion and some metabolites were also determined in
urine by LC-MS/MS in a fatal overdose case where this antidepressant was involved
[ 70 ]. LC-MS/MS was also applied to the analysis of other typical postmortem
specimens, including gastric content, bile, vitreous humor, cerebrospinal fluid,
brain, liver, lungs, kidney, or muscle, usually for the determination of one antide-
pressant and its main metabolite [ 38- 40 ] . Goeringer et al. [ 57 ] extended the num-
ber of analytes included in the method to seven antidepressants, some metabolites
and one antipsychotic in different forensic specimens. Unfortunately, validation
performed in most of these methods was poor and, sometimes, only described for
some of the analyzed specimens.
Few authors described antidepressant analysis in alternative specimens, such
as hair or oral fluid. LC-CID-MS and MS/MS mass spectra libraries for
identification of several drugs were employed by Müller et al. [ 32 ] for the detec-
tion of maprotiline, citalopram, and their desmethyl metabolites in authentic hair
specimens; extracted ions chromatograms were employed for subsequent antide-
pressant quantification. Also Klys et al. [ 33 ] applied LC-MS/MS to the analysis
of blood, urine, and hair specimens in a fatal case due to clomipramine overdose
in combination with alcohol. Blood clomipramine and norclomipramine concen-
trations explained the fatal outcome, and hair analysis confirmed that the deceased
was on clomipramine treatment for, at least, 12 months prior to his death. With
regard to oral fluid analysis, de Castro et al. [ 34 ] developed and validated a
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