title: LC-MS/MS method for the determination of nine antidepressants and some of their main metabolites in oral fluid and plasma. Study of correlation between venlafaxine concentrations in both matrices.
abstract: In this paper, a fast, sensitive and selective LC-MS/MS method is described for the simultaneous determination of amitriptyline, imipramine, clomipramine, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and venlafaxine, as well as some of their main metabolites (nortriptyline, desipramine, norclomipramine and norfluoxetine), in oral fluid and plasma. The sample (0.2 mL) was extracted with an automated solid-phase extraction system (ASPEC XL), using mixed mode OASIS MCX cartridges. Chromatographic separation was performed in a Sunfire C18 IS column (20 mmx2.1 mm, 3.5 microm), using a gradient of acetonitrile and ammonium formate (pH 3; 2 mM) as mobile phase, which allowed the elution of all the compounds in less than 5 min. The method has been fully validated in both specimens. This method was initially applied to the analysis of oral fluid and plasma samples from patients on antidepressant treatment in order to assess for which compounds it was likely to find a good correlation between both matrices. The best results were obtained for venlafaxine, so the study was extended for this compound, comparing the ratio between oral fluid and plasma concentrations (ROF/PL) in five patients on venlafaxine treatment when both samples were collected simultaneously on four different occasions. An important inter and intraindividual variability was found in oral fluid concentrations for 150 mg dose (mean=287.5 ng/m, range 58.8-531.2 ng/mL) and for 75 mg dose (mean=186.3 ng/mL, range=82.1-289.2 ng/mL). R(OF/PL) was calculated for each patient on the four different occasions, showing also a high variability (CV=24.2-69.6%).
authors.affiliation: Forensic Toxicology Service, Institute of Legal Medicine of the University of Santiago de Compostela, C/San Francisco s/n, 15782 Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: de Castro
authors.forename: M
authors.initials: M
authors.lastname: Concheiro
authors.forename: O
authors.initials: O
authors.lastname: Quintela
authors.forename: A
authors.initials: A
authors.lastname: Cruz
authors.forename: M
authors.initials: M
authors.lastname: López-Rivadulla
mesh_terms: D000928:Antidepressive Agents / Q000097:blood* / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D003511:Cyclohexanols / Q000097:blood* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D012463:Saliva / Q000737:chemistry*; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride