Biomedical Engineering Reference
In-Depth Information
Nevertheless, reliable methods using the SIM mode were introduced for TA
analysis. The SIM mode was used for analysis of atropine and scopolamine from
human viscera [
15
] and human plasma [
11
] (Table
8
), of tropisetron from liver
microsomal incubation mixtures [
82
] (Table
7
), of granisetron from rat plasma [
72
] ,
of hyoscyamine enantiomers from human plasma [
48
], of scopolamine from rabbit
plasma [
89
], of tiotropium from human plasma [
81
] (Table
5
) and of atropine from
dog plasma [
96
] (Table
6
). The corresponding values for the monoisotopic
molecular weight (MW) and the corresponding
m
/
z
-values of protonated TTA and
pure QTA are summarized in Table
9
.
However, the SIM technology was only applied with minor frequency of all scan
modes (17 %) (Fig.
5b
).
3.3.3.3
Product Ion Scan
The product ion scan provides the entire information on product signals and thus
allows structural assignment by diagnostic ions or by comparison to spectral data
bases [
108
]. This scan mode was a highly valuable tool for confirmative identification
of novel in vivo biotransformation products from diverse TTA as elaborated by
Chen et al. for anisodamine [
6
] , anisodine [
5
] , atropine [
51,
52
] , and scopolamine
[
7,
87
]. The strategy and principle of these studies including “neutral loss” and
“precursor ion scans” will be discussed below in Sects.
3.4.3
. Table
9
summarizes
m
/
z
-values of the most dominant product ion signals of TTA and QTA referred to
in this chapter.
No examples for quantification in the product ion scan mode were found in the
literature even though data processing would allow extraction of selected ions,
integration of related signal areas, and summation for quantification. This proce-
dure has been used by John et al. for the determination of the human haemoglobin
derived peptide hHEM-g 130-146 in plasma [
102
] . However, quanti fi cation espe-
cially of small molecule analytes is best performed in the MRM mode that is
addressed below.
3.3.3.4
Multiple Reaction Monitoring
MRM is the most frequently used scan mode (61 % of all applications, Fig.
5b
)
predestinated for most selective and highly sensitive quantification. Typically, QqQ
systems were used even though IT spectrometers are also capable for this scan
mode. More rapid scan rates and superior linear range are commonly accepted pref-
erences of the QqQ design.
In principle, simple quantification only requires to monitor one transition from
the precursor to one product ion (quantifying ion). The resulting selectivity is often
very satisfying but should be improved by additional monitoring of at least a
second transition from the precursor to a second product ion (qualifying ion).
