Aim: Objective of the current work was to develop a 'green chemistry' compliant selective and sensitive supercritical fluid chromatography-tandem mass spectrometry method for simultaneous estimation of risperidone (RIS) and its chiral metabolites in rat plasma. Methodology & results: Agilent 1260 Infinity analytical supercritical fluid chromatography system resolved RIS and its chiral metabolites within runtime of 6 min using a gradient chromatography method. Using a simple protein precipitation sample preparation followed by mass spectrometric detection achieved a sensitivity of 0.92 nM (lower limit of quantification). With linearity over four log units (0.91-7500 nM), the method was found to be selective, accurate, precise and robust.
Conclusion: The method was validated and was successfully applied for simultaneous estimation of RIS and 9-hydroxyrisperidone metabolites (R & S individually) after intravenous and per oral administration to rats.
Keywords: 9-hydroxyrisperidone; SFC–MS/MS; chiral metabolites; pharmacokinetics; risperidone; supercritical fluid chromatography.