IntroductionFluvoxamine, 5-methyl-4′-trifluoromethylvalerophenone(E)-O-2-aminoethyloxime monomaleate, is one of several antidepressant agents known as selective serotonin reuptake inhibitors (SSRIS). The efficacy of fluvoxamine in depression has been reviewed in previous papers. 1,2 The clinical pharmacokinetics of fluvoxamine were also described in a previous paper. 3 Negligible amounts of fluvoxamine are excreted unchanged in the human urine. Urinary fluvoxamine metabolites have been identified as consisting of at least 9 different compounds. About 65% of these metabolites resulted from oxidative demethylation of the aliphatic methoxyl group, and 15% of metabolites are formed by degradation at the primary amino group. Fluvoxamino acid is the main primary metabolite in humans. 4 Therefore, the monitoring of fluvoxamino acid on the drug interaction study of fluvoxamine will be able to detect slight changes of fluvoxamine metabolism by co-administered drug in healthy volunteers and/or patients.The pharmacokinetics of fluvoxamino acid in human has not yet been studied sufficiently.Methods for the fluvoxamine by GC-MS, 12 HPLC with liquidliquid extraction of plasma samples [13][14][15][16][17] and HPLC with solidphase in-line extraction 18,19 were described in previous papers. The liquid-liquid extraction methods are not completely satisfactory because they are time-consuming and require a tedious procedure. We have reported a simple extraction method of several drugs and their metabolites by using a solid phase extraction cartridge. [20][21][22][23] However, an off-line solid phase extraction method for fluvoxamine has not been reported in previous papers. There is also no report for simultaneous determination of fluvoxamine and fluvoxamino acid in human plasma by HPLC.The extraction of fluvoxamine and fluvoxamino acid in human plasma using a solid phase method has some problems: one is the simultaneous extraction from a complex mixture of both acidic and basic compounds. Therefore, a specific extraction method and an efficient chromatographic system without interfering peaks was needed 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 (C...