Quantification of risperidone and 9-hydroxyrisperidone in plasma and saliva from adult and pediatric patients by liquid chromatography–mass spectrometry

A robust and validated LC–MS–MS quantitative method, using column switching and mutiple reaction monitoring was developed for the analysis of risperidone (RIS) and 9-hydroxyrisperidone in human plasma and saliva. The analytical range was 1–100 ng/ml. The method used 25 μl of sample precipitated with 75 μl of acetonitrile containing internal standard (R068808). Analyses were conducted on a PE Sciex API-III+triple quadrupole mass spectrometer fitted with a Turbo IonSpray source. The method was validated for human plasma using EDTA as the anticoagulant and cross-validated to heparinized human plasma and saliva. The recoveries of risperidone and 9-hydroxyrisperidone were 90–93 and 89–93%, respectively. The validated method was applied to clinical samples to study risperidone and 9-hydroxyrisperidone concentrations in plasma and saliva. Risperidone and 9-hydroxyrisperidone appear in the saliva of patients treated with risperidone. Their detection/quantification in saliva provides evidence for recent adherence with therapy.