Biomedical Engineering Reference
In-Depth Information
whereas both QTA (ipratropium and
N
-butyl-scopolamine) remained unaffected.
Furthermore, as mentioned above, atropine was degraded to half of its initial
concentration due to the enzymatic stereoselective preference for
S
-hyoscyamine
(Fig.
4
). This enzyme activity is solely found in rabbits and explains the animals'
high tolerance towards ingested plants of the
solanaceae
family (e.g. deadly
nightshade) that are in general toxic to other mammals [
114,
115
] .
This aspect of poisoning is addressed in the last section introducing LC-MS
methods for toxicological and forensic screening to detect toxic TA in body fluids
after drug abuse or ingestion of toxic plants.
3.4.4
Toxicological Screening and Evidence of Drug Abuse
In contrast to PK or biotransformation studies that require detection of known or at
least postulated compounds, toxicological screenings appear much more sophisti-
cated. In general, the drugs or poisons as well as their concentrations in body fluids
are unknown and thus require elaborated and reliable analytical tools for initial
unambiguous identification and subsequent quantification. Specifications for post-
mortem analysis are even higher [
113
]. Toxicological judgment and clinical or
forensic consulting demands authoritative analysis.
Even though LC-MS/MS procedures promise an optimum of selectivity, care-
ful validation of the entire procedure is mandatory for a highly selective, sensi-
tive, accurate and coherent analysis [
116
]. Therefore, validation of LC-MS
methods should address selectivity, calibration model (linearity), stability (long-
term, freeze and thaw, benchtop), accuracy, precision, LOQ, LOD, recovery,
reproducibility, ruggedness and matrix effects [
117
]. Matrix effects represent a
highly critical issue in bioanalysis especially for trace analysis when performing
ESI that is highly susceptible for these deteriorating phenomena. Ion suppression
might be the most frequent impact of co-eluting IS or compounds derived from
the matrix. Especially analytes of lowest concentrations might be overseen. To
prevent from false results appropriate sample preparation and clean-up have to
be worked out.
Very often plasma or serum is used for quantitative purposes allowing correlation
to pharmacological or toxicological effects. Even though oral fluid is regarded as
alternative to plasma for drug screening it is not capable for TTA and QTA analysis
as these compounds are ionized and do thus not correlate to plasma concentrations
[
116
]. Therefore, no LC-MS-based applications were found for oral fluid as sum-
marized in Table
8
. Furthermore, atropine intoxication for example causes dry
mouth and thus makes sample taking by spitting quite difficult.
In addition, hair might represent a valuable specimen for confirmation of drug
abuse [
95
] even though specific pitfalls should be avoided for reliable measurement
[
94
] . Table
8
refers to two LC-MS/MS methods that were used to detect atropine
and scopolamine in hair [
56,
57
] .
Finally, urine is also an important body fluid to detect drug and poisons and their
corresponding biotransformation products. However, correlation of concentrations
