Analytical Sciences

High-Performance Liquid Chromatographic Determination of Fluvoxamine and Fluvoxamino Acid in Human Plasma

Tadashi OHKUBO,*  Ritsuko SHIMOYAMA,* Koichi OTANI,** Keizo YOSHIDA,*** Hisashi HIGUCHI,*** and Tetsuo SHIMIZU***

*Department of Pharmacy, Hirosaki University Hospital, Hirosaki 036-8563, Japan
**Department of Neuropsychiatry, Yamagata University Hospital, Yamagata 990-9585, Japan
***Department of Neuropsychiatry, Akita University Hospital, Akita 010-8543, Japan

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of fluvoxamine and its major metabolite fluvoxamino acid in plasma. Fluvoxamine and fluvoxamino acid in plasma were extracted using a C₁₈ bonded-solid phase cartridge, followed by C₄ reversed-phase HPLC separation. Fluvoxamine, fluvoxamino acid and moperone as an internal standard were detected by ultraviolet absorbance at 254 nm. It was possible to determine both fluvoxamine and fluvoxamino acid in the concentration range of 25.0 - 200.0 ng/mL, respectively. The detection limits of both fluvoxamine and fluvoxamino acid were 10.0 ng/mL, respectively. The mean recoveries of fluvoxamine and fluvoxamino acid added to plasma were more than 94.0% and 96.5%, with a coefficient of variation of less than 7.6% and 8.2%, respectively. This method has been used for the simultaneous determination of steady-state plasma concentration (Css) of fluvoxamine and fluvoxamino acid in depressive patients treated with 200 mg of oral fluvoxamine dosed as 100 mg twice-daily. The Css values of fluvoxamine and fluvoxamino acid in twelve Japanese patients were showed individual variations, which were in the range of 48.3 - 532.9 ng/ml and 35.6 - 307.1 ng/ml, respectively.

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