Biomedical Engineering Reference
In-Depth Information
misidentification. Several methods that allow for high sample throughput due to
short run times monitor only one transition per compound, as peak widths would
be too small in order to include a sufficient number of data points per peak in the
given cycle time.
All analytical methods must be validated in accordance with international guide-
lines [
59-
61
] prior to application. As discussed in the first part of this topic, mini-
mum criteria that need to be met to in order to satisfy these guidelines are: selectivity,
matrix effects, extraction efficiency, process efficiency, processed sample stability,
linearity, accuracy, precision, and freeze-thaw stability.
Table
2
shows a selection of published TDM methods. All methods presented
use plasma or serum, with volumes ranging from 0.06 mL [
46
] to 0.5 mL [
45,
62
] .
Berna et al. include several olanzapine metabolites in their detection method,
while most other methods target one or very few analytes. Appropriate IS (i.e.,
deuterated analogs of APs or nondeuterated drugs which are not in therapeutic
use) are used in three of the five presented methods. However, one method uses
prazosin [
62
], a sympatholytic antihypertensive drug, while the other uses sulpir-
ide [
63
]. This can cause problems including underestimation of the target drug as
previously discussed in this chapter. Liquid-liquid extraction, solid phase extrac-
tion, and protein-precipitation are used in the presented methods, some in combi-
nation with a 96-well plate format in order to accommodate for a high sample
throughput. RP columns are common with one approach applying a chiral column
[
53
] in order to separate the two enantiomers (+) 9-OH-risperidone and (−)
9-OH-risperidone. Both isocratic and gradient elution are applied for drug separa-
tion. All methods use MRM mode for compound identification; however, only
one transition is monitored in all presented methods. International guidelines rec-
ommend to include a minimum of two transitions per analyte in order to lower the
risk of misidentification of a drug. The “validation data” presented in Table
2
shows which validation experiments have been performed by the respective
authors. Before adapting a method for use in a laboratory, one should check the
method validation for completeness (according to the international guidelines
presented earlier in this chapter) and perform additional validation experiments
where applicable.
2.4
Stability of Antipsychotic drugs
It is desirable to also investigate long-term stability of samples under different
storage conditions prior to release of a method. This is particularly important
when samples are not analyzed promptly after admission to a laboratory, or
reanalysis of specimens is required due to additional tests becoming necessary.
There is limited data available on the stability of APs in stored blood samples.
The only comprehensive study investigating the stability of 30 commonly
prescribed APs in whole blood was published in 2011 [
64
] . Four different stor-
age temperatures (20, 4, −20, −60 °C) and two concentration levels were included
