Simultaneous determination of fluvoxamine isomers and quetiapine in human plasma by means of high-performance liquid chromatography

An original HPLC-UV method has been developed for the simultaneous determination of the atypical antipsychotic quetiapine and the geometric isomers of the second-generation antidepressant fluvoxamine. The analytes were separated on a reversed-phase C8 column (150×4.6 mm I.D., 5 µm) using a mobile phase composed of acetonitrile (30%) and a 10.5 mM, pH 3.5 phosphate buffer containing 0.12% triethylamine (70%). The flow rate was 1.2 mL/min and the detection wavelength was 245 nm. Sample pretreatment was carried out by an original solid-phase extraction procedure using mixed-mode cation exchange (DSC-MCAX) cartridges; only 300 µL of plasma were needed for one analysis. Citalopram was used as the internal standard. The method was validated in terms of linearity, extraction yield, precision and accuracy. Good linearity was obtained in plasma over the 5.0-160.0 ng/mL concentration range for each fluvoxamine isomer and over the 2.5-400.0 ng/mL concentration range for quetiapine. Extraction yield values were always higher than 93%, with precision (expressed as relative standard deviation values) better than 4.0%. The method was successfully applied to human plasma samples drawn from patients undergoing polypharmacy with the two drugs. Satisfactory accuracy values were obtained, with mean recovery higher than 94%.