Biomedical Engineering Reference
In-Depth Information
APs are present in biological specimens (see Table
1
for therapeutic concentra-
tions of common APs).
In recent years, liquid chromatography (LC) instruments combined with a variety
of MS mass analyzers (quadrupole, Time-of-Flight (TOF), Ion Trap) have become
more affordable and widespread in clinical and forensic toxicology. Since HPLC
does not require volatilization or derivatization, this has led to the widespread use of
LC-MS for the detection of APs in biological matrices. More and more laboratories
are now able to provide such testing as part of a routine toxicological service includ-
ing therapeutic drug monitoring (TDM).
2.2
Biosamples
Analysis of APs in human specimens is particularly important in both a clinical and
forensic setting: In a clinical environment, AP analysis is necessary in order to mon-
itor patient compliance and to maintain drug concentrations within the recom-
mended therapeutic range of the respective drug. In a medicolegal setting involving
postmortem analysis, the determination of APs is essential in assisting to establish
whether these drugs played a role in a person's death. The absence of prescribed
APs in a clinical case may also indicate noncompliance, ultimately resulting in an
altered mental state and an increased risk of sudden death. In forensic cases, this
noncompliance may be especially relevant in cases where behavioral disturbances
lead to the death of a person by another, e.g., homicides.
Urine is the specimen of choice for screenings to show the presence of a particular
compound qualitatively. Therefore, published methods for detection in urine [
27-
30
] ,
as well as the less common specimens, namely, saliva [
31
] , and cerebrospinal fl uid
[
32
] are rare and not reviewed in this topic chapter. Hair is the specimen of choice
when a larger surveillance window is required. Segmental hair analysis in particular
can give a good indication of the history of drug use in an individual. While hair
analysis is frequently used as a tool in the analysis of drugs of abuse, only a limited
number of methods using LC-MS(/MS) technology targeting APs in hair have been
published to date [
29,
33-
37
]. Most of these methods show no or very limited method
validation and are not used in routine toxicological testing.
2.3
Approaches to the Detection of APs in Human Biological
Matrices
Blood is most commonly used for the analysis of APs as drug concentrations in
blood represent a more accurate correlation with pharmacological effects than in
any other specimen. Plasma or serum is usually obtained from clinical samples,
as blood cells can easily be separated from liquid components to create a “cleaner”
