Author(s): Duverneuil C, de la Grandmaison GL, de Mazancourt P, Alvarez JC
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Abstract A new rapid and sensitive high-performance liquid chromatography method has been developed for the screening and determination in human plasma of the 11 most commonly prescribed nontricyclic antidepressants and two metabolites: fluoxetine, norfluoxetine, sertraline, paroxetine, citalopram, fluvoxamine, moclobemide, mirtazapine, milnacipram, toloxatone, venlafaxine, desmethyl venlafaxine, and viloxazine. It involves liquid-liquid extraction procedures followed by liquid chromatography coupled to photodiode-array UV detection with three fixed wavelengths (220, 240, and 290 nm). Compounds were separated on a 5-microm Hypurity C18 (ThermoHypersil) analytic column (250 x 4.6 mm i.d.) using a gradient of acetonitrile-phosphate buffer pH 3.8 at a flow rate of 1.0 mL/min. The total analysis time was only 18 min per sample. Extraction recoveries were in the 74-109\% range for 11 compounds but were of only 59\% for moclobemide and less than 10\% for toloxatone. Calibration curves were linear in the 25 to 1000 ng/mL range for all compounds, all of them with coefficients of determination (r2 values) > or = 0.999. Limits of detection (LODs) ranged from 2.5 to 5 ng/mL except for toloxatone (10 ng/mL). Intraassay and interassay precision and accuracy were studied at two concentration levels (50 and 500 ng/mL). The intraassay coefficients of variation (CVs) for all compounds were < or = 7.6\%, and all interassay CVs were below 11.5\% except for milnacipram (14.8\%). The intraassay and interassay accuracies for all compounds were found to be within 88.4\% and 105.9\% at 50 ng/mL and within 87.2\% and 100.5\% at 500 ng/mL. The performance of the method allows the therapeutic drug monitoring of the most prescribed nontricyclic antidepressant drugs as well as its use in toxicologic screening.
This article was published in Ther Drug Monit
and referenced in Journal of Proteomics & Bioinformatics