Biomedical Engineering Reference
In-Depth Information
LC-MS/MS procedure for the determination of the main marketed antidepressants
in plasma and oral fluid to assess the possible correlation between the concentra-
tions found in these two biological matrices. Also Coulter et al. [
35
] validated a
LC-MS/MS methodology for several antidepressants and two other psychophar-
maceuticals in oral fluid for its application to driving under the influence of drugs
(DUID) cases.
6
LC-MS/MS Method for the Determination of Nine
Antidepressants and Some of their Main Metabolites
in Oral Fluid and Plasma
An LC-MS/MS method [
34
] will be described in detail in order to serve as an
example of method development and validation. This method allows the determina-
tion of some of the most common antidepressants used in clinical practice and some
of their main metabolites in oral fluid and plasma samples.
Plasma is the main biological sample used in clinical and toxicological analysis,
as concentrations found in this matrix are correlated to the pharmacological effect,
as well as to the side and toxic effects. However, oral fluid has also been employed
in some specific applications because of the advantages associated to this alternative
specimen: easy, painless, and noninvasive collection, which does not require
qualified personnel, it represents the free analyte fraction, and it has a window of
detection similar to that in plasma. Within the possible applications of oral fluid
analysis, two are of special relevance:
1. Detection of subjects driving under the in fl uence of sedative antidepressants
effects.
2. TDM: As previously stated in this chapter, TDM is recommended for TCAs and,
in special situations, for the new generations of antidepressants. However, several
factors can affect diffusion of the analytes from plasma to oral fluid (pH, oral
contamination, collection with or without stimulation). Therefore, the correlation
between antidepressant plasma and oral fluid concentrations should be studied
before using this alternative specimen for TDM purposes.
An example of method application to a study to assess the possible correlations
between antidepressant concentrations in plasma and oral fluid will also be discussed
in this section.
6.1
LC-MS/MS Method
A Waters Alliance 2795 Separation Module with a Waters Alliance series column/
heater (Waters Corp., Milford, MA) was employed, using a Sunfire C18 (20 mm × 2.1
mm, 3.5 mm) Intelligent Speed™ column (Waters Corp., Milford, MA) for chro-
