Determination of risperidone and 9-hydroxyrisperidone in human plasma by high-performance liquid chromatography: application to therapeutic drug monitoring in Japanese patients with schizophrenia

A high-performance liquid chromatographic method has been developed for the simultaneous determination of risperidone and its major active metabolite 9-hydroxyrisperidone in plasma. Risperidone and 9-hydroxyrisperidone in pla sma were extracted using a CN bonded-solid phase cartridge, followed by, C4 reversed-phase HPLC separation. Risperidone, 9-hydroxyrisperidone and traz odone as an internal standard were detected by ultraviolet absorbance at 28 0 nm. It was possible to determine risperidone in the concentration range o f 1.0-100.0 ng ml(-1) and 9-hydroxyrisperidone at a range of 2.0-200.0 ng m l(-1). The detection limits of risperidone and 9-hydroxyrisperidone were 0. 5 and 1.0 ng ml(-1), respectively. The mean recoveries of risperidone and 9 -hydroxyrisperidone added to plasma were less than 92.0 and 92.6%, with a c oefficient of variation of less than 10.6 and 10.5%, respectively. This met hod has been used for the simultaneous determination of steady-state plasma concentration (Css) of risperidone and 9-hydroxyrisperidone in schizophren ic patients treated with 3-, 6-, and 12-mg risperidone oral doses per day. (C) 1999 Elsevier Science B.V. All rights reserved.