Simultaneous determination of new-generation antidepressants in plasma by gas chromatography–mass spectrometry

Abstract

We have developed a gas chromatography–mass spectrometry (GC–MS) method for plasma for the determination of new-generation antidepressants, including olanzapine (antipsychotic used in bipolar disorder), and antidepressant selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine and its metabolite norfluoxetine, paroxetine, sertraline, venlafaxine, and mirtazapine. Sample preparation was performed by liquid–liquid extraction with tert-butyl methyl ether. Fluoxetine, norfluoxetine, sertraline, and paroxetine required subsequent derivatization with 1-(heptafluorobutyryl) imidazole (HFBI). The GC separation lasts a total of 23.76 min. Qualitative and quantitative analysis were performed using an electron-impact ionization gas chromatograph interfaced to a mass-selective detector in selected-ion monitoring mode to increase the sensitivity of the method. Method validation was performed taking into account linearity, sensitivity, selectivity, accuracy, precision, and recovery, achieving good results for all the parameters studied. Calibration curves were prepared in the range of 0.005–2 μg/ml (according to the therapeutic and toxic concentrations of each individual compound), with all correlation coefficients R2 > 0.99. The limit of quantification was between 0.005 and 0.1 μg/ml, depending on the compound, whereas the limit of detection ranged from 0.0025 to 0.05 μg/ml. The method is fast and simple, allowing the identification and quantification of some of the most widely used antidepressants at therapeutic or toxic concentrations, and may be useful in routine clinical and forensic toxicology analysis.