Methods for the determination of seven selective serotonin reuptake inhibitors and three active metabolites in human serum using high-performance liquid chromatography and gas chromatography

This paper describes a set of simple and sensitive multitesidue methods for the determination of the specific serotonin reuptake inhibitors (SSRIs) used as antidepressant drugs, and some of their respective active metabolites in human serum. It involves liquid-liquid extraction procedures followed by gas chromatography coupled to nitrogen phosphorus detection or isocratic reversed-phase high-performance liquid chromatography combined with fluorescence detection (HPLC-FL), depending on the analytes. Extraction recoveries were between 71 and 96% for the eight SSRIs and their metabolites analysed by GC and between 41 and 77% for the two of them analysed by HPLC. Limits of detection (LODs) and limits of quantitation (LOQs) ranged, respectively: from 2.5 to 5 mu g/l and from 10 to 20 mu g/l. Intra-assay and inter-assay precision was studied at three and four concentration levels, respectively, and was less than 19% for all compounds. Accuracy was also satisfactory for all. An excellent linearity was observed from the LOQs up to 1000 mu g/l for milnacipram and paroxetine and from each LOQ up to 400 mg/l for the other compounds. The performance of the methods described thus allows the therapeutic drug monitoring of the currently commercialised SSRIs. (C) 2000 Elsevier Science B.V. All rights reserved.