Biomedical Engineering Reference
In-Depth Information
[
45-
47
]. In one study, daily opioid doses significantly decreased in a gene
dose-dependent manner with the ABCB1 3435C>T variant [
45
] . The same study
found that a tendency toward increased pain and the OPRM1 118A>G variant were
associated in a dose dependent manner [
45
]. Another study found that pain relief
variability was significantly associated with both polymorphisms [
46
] .
2.3.3
Analytical Assays and Need for TDM Measurements for Drug
Compliance
Serum or plasma assays for prescription opioids are not routinely used for thera-
peutic drug monitoring in the clinical laboratory. The current testing strategy
includes urine screening with immunoassays followed by targeted confirmations
with gas chromatography mass spectrometry (GC-MS) or liquid chromatogra-
phy tandem mass spectrometry (LC-MS/MS). These assays are used to monitor
drug use and compliance of prescribed opioids because of the long detection
window of the metabolites in urine. However, serum and plasma assays for opioids
have many advantages over urine because the opioid level in these matrices is
reflective of the patient's clinical state at the time of blood collection. The levels
could be used for titrating dose, determining steady-state concentrations or
determining the drug and metabolite levels in cases of suspected opioid toxicity.
However, the role of TDM in titration and monitoring opioids is not well defined.
There are no current practice guidelines that have been established for clinical
use. Many opioids meet the general criteria for TDM including a narrow thera-
peutic index, a poor relationship between drug dose and blood concentration,
significant inter-individual variation and a serious consequence for overdosing
in some individuals. In a study conducted by Lotsch and colleagues they con-
cluded that in order for codeine therapy to be safe, prediction of morphine for-
mation must be obtained by combining
CYP2D6
genotyping with phenotyping
[
34
]. Phenotyping can account for the other genetic and nongenetic factors
listed in Sect.
2.3.2
.
Despite the fact that opioid TDM is not routine in the clinical laboratory, there
are several published methods for the detection of opioids in serum or plasma using
LC-MS/MS [
48-
52
]. LC-MS/MS is capable of detecting polar and thermally labile
compounds and thus has advantages over GC-MS for the analysis of opioids. Parent
drugs and glucuronide metabolites can be quantitated in the same method. With
LC-MS/MS, sample preparation is decreased because there is no need for hydroly-
sis. These LC-MS/MS methods are commonly used in forensic settings and for
research purposes. They include anywhere from 6 to 24 opioids and their metabo-
lites and have lower limits of quantitation down to approximately 0.5 ng/mL for
many of the analytes. One method demonstrated an upper limit of quantitation at
2,500 ng/mL [
48
]. These methods are sufficient for determining opioid and metabo-
lite levels and could be used for TDM in the clinical setting once further studies are
conducted to establish appropriate guidelines.
