Improved HPLC determination of flouxetine and norflouxetine in human plasma

An HPLC method with florescence detection has been developed for the determination of flouxetine and its main metabolite norflouxetine in human plasma. Pretreatment of the biological samples by liquid-liquid extraction was used to improve the sensitivity of a previously published SPE procedure. The method uses 200 ?L plasma and recovery is good for both analytes. On a C8 column with a mixture of perchlorate buffer and acetonitrile as mobile phase flouxetine, norflouxetine and the internal standard (paroxetine) were eluted in less than 9 min, without interference from the biological matrix. Response for both analytes was linearly dependent on concentration over the range 2.5-500 ng mL-1, and repeatability (RSD%) was <4%. The limit of detection was 1 ng mL-1 for both fluoxetines. Application to plasma samples from depressed patients treated with flouxetine gave good results. There was no interference from other common CNS drugs. This method seems to be a useful tool for clinical monitoring, because it requires small plasma samples and is highly sensitive and highly selective.