Biomedical Engineering Reference
In-Depth Information
in this study. Whilst low storage temperatures such as −20 and −60 °C appeared
to be preferable for storage of samples containing APs, the low temperatures did
not guarantee stability for all investigated drugs. The commonly used atypical
AP olanzapine (Fig.
2
VI) has been associated with severe stability issues not
only in stored whole blood [
43,
48
] , serum [
65
] , and plasma [
66
] , but also under
the conditions of analysis [
41
]. Oxidation of the thiophene-ring has been
suggested as a possible cause of instability but this theory has not been confirmed.
A loss greater than 70 % of the initial olanzapine concentration was observed
under all four storage temperatures in less than a week. Addition of ascorbic acid
as an antioxidant has been suggested in order to prevent degradation, but is not
always practical. Ziprasidone showed losses of ~85 % after storage for ten weeks
at 20 °C, whereas storage at lower temperatures was not affected by degradation.
One needs to be aware that inappropriate storage of samples containing ziprasi-
done—even for a short time—can result in significant concentration changes.
3
Conclusions
When analyzing APs in human biological specimens, various factors need to
be considered. Due to the large number of APs currently on the market, multiana-
lyte methods are preferred over single-analyte methods. Analytical methods need to
be sensitive enough to cover the low therapeutic range in which APs can be present.
Also, validation in accordance with international guidelines needs to be undertaken
in order to obtain reproducible results. When adapting a previously developed
method for use in a different laboratory, sufficient cross-validation must be carried
out prior to use. Sample integrity needs to be preserved by appropriate storage and
it is advisable to have knowledge about concentration changes of APs after different
storage times. When interpreting results, it is not sufficient to compare obtained
concentrations to target ranges of a drug, but cofactors such as sampling time,
dosage history, half-life of a drug, comedication, and genetic variations amongst
individuals, need to be taken into consideration.
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