Biomedical Engineering Reference
In-Depth Information
paroxetine [
85
] determination, respectively. HILIC columns allow adequate
retention of polar analytes poorly retained by reversed-phase chromatography,
while still retaining less polar analytes; moreover, the high organic composition
of the mobile phase increases electrospray efficiency, thus providing higher
sensitivity. Chiral stationary phases were employed for enantioselective analysis
of antidepressants marketed as a racemic mixture such as fluoxetine, citalopram,
venlafaxine, mirtazapine, or bupropion [
42,
43,
82,
88,
89
] .
Analytical methods for the determination of one antidepressant and/or its
metabolite(s) were usually performed in isocratic mode, with total run times from
seconds to a few minutes. However, as previously mentioned, multianalyte procedures
are preferable, particularly if the method is intended for clinical or forensic analysis.
Gradient separation was usually applied when the most common antidepressants were
included in the methodology; however, total chromatographic run times varied widely,
from 5 to 40 min [
57,
76
], depending on column length, extraction technique (offline
vs. online techniques), biological matrix or the specific application of the method.
4
Mass Spectrometry Characteristics for Antidepressants
LC-MS(MS) Analysis
4.1
Atmospheric Pressure Ionization Interfaces
Several LC-MS interfaces have been developed since 1974, when Arpino et al. [
90
]
described the first attempt to couple the LC system to the mass spectrometer. Some
of them were commercialized [
91
], but it was the development of atmospheric
pressure ionization interfaces (API) which actually lead to the great expansion of
LC-MS applications.
Within API interfaces, electrospray ionization (ESI) is the preferable ionization
method for polar analytes, and it was used in the great majority of LC-MS methods
for antidepressants analysis. However, ESI interfaces are more susceptible to matrix
effects than atmospheric pressure chemical ionization (APCI) [
54,
92,
93
] due to
differences in the ionization process. ESI is based on liquid phase reactions, where
ion suppression is more likely than in gas phase due to high concentrations of non-
volatile materials present in the spray with the analyte [
92
]. Because of the lower
susceptibility for matrix effects, although few, there have been authors who selected
APCI as ionization mode in spite of the lower sensitivity for these analytes [
59,
62,
74,
75
]. Although ESI and APCI are by far the most popular ionization methods,
other alternative interfaces were used for antidepressant analysis. Shinozuka et al.
[
69
] used sonic spray ionization (SSI), a variant of ESI, where ionization is produced
by high sonic gas velocity during pneumatic nebulization, instead of the electric field
and capillary high temperatures applied in ESI. Atmospheric pressure photoioniza-
tion (APPI) is a novel interface originally developed to widen the group of analytes
to be determined by LC-MS towards less polar compounds that are not efficiently
