Analysis of risperidone and its metabolite in plasma and saliva by LC with coulometric detection and a novel MEPS procedure.
A new analytical method, based on the use of liquid chromatography with coulometric detection, has been developed and applied to quantify risperidone and its main active metabolite 9-hydroxyrisperidone in human plasma and saliva. The analytes were separated on a reversed phase C18 column, using a mobile phase composed of acetonitrile (26%) and a pH 6.5 phosphate buffer (74%). Pipamperone was used as the internal standard. A high sensitivity coulometric detection analytical cell containing two flow-through working electrodes was used: electrode 1 was set at +0.500V and electrode 2 at +0.700V. The detector response was linear over a plasma and saliva concentration range of 0.5-50.0ngmL(-1) for risperidone and 0.5-100.0ngmL(-1) for 9-hydroxyrisperidone. The limit of quantitation and the limit of detection for risperidone and 9-hydroxyrisperidone were 0.5ngmL(-1) and 0.17ngmL(-1), respectively. A novel clean-up procedure of biological samples was developed using the microextraction by packed sorbent technique, which gave good extraction yield for both the analytes, with absolute recovery values higher than 90.1%. The intra-day and the inter-day precision results, expressed by relative standard deviation values, were lower than 5.8%. Accuracy and selectivity assays were also satisfactory. The validated method has been successfully applied to the analysis of risperidone and 9-hydroxyrisperidone in plasma and saliva of psychiatric patients undergoing therapy with risperidone.
Saracino
Maria Addolorata
MA
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, Bologna, Italy.
de Palma
Anna
A
Boncompagni
Giancarlo
G
Raggi
Maria Augusta
MA
D000328:Adult; D002138:Calibration; D002623:Chemistry Techniques, Analytical; D002853:Chromatography, Liquid / Q000379:methods*; D003124:Colorimetry / Q000379:methods*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D004364:Pharmaceutical Preparations; D015203:Reproducibility of Results; D018967:Risperidone / Q000032:analysis* / Q000097:blood* / Q000378:metabolism; D012463:Saliva / Q000187:drug effects*; D012680:Sensitivity and Specificity; D052617:Solid Phase Microextraction
D004364:Pharmaceutical Preparations; D018967:Risperidone