Liquid Chromatography/tandem Mass spectrometry Method for the Simultaneous Determination of Risperidone and its Active Metabolite, hydroxyrisperidone: Pharmacokinetics Study of Three Different Dose Levels.

Antipsychotics, risperidone (RIS), and risperidone’s active metabolite, paliperidone (9-hydroxyrisperidone) (9-OH- RIS), are related molecules used for the treatment of schizophrenia and related disorders. A sensitive and specific liquid-chromatography tandem mass spectrometry (LC-MS/MS) assay has been developed and validated for simultaneous quantification of (RIS) and its active metabolite (9-OH- RIS) in rat plasma. After a simple one step protein precipitation by acetonitrile, RIS, its active metabolite (9-OH- RIS) and olanzapine as internal standard (IS) were separated on Acquity UPLC BEHTM C18 (20X2.1 mm, i.d 1.7 µm, Waters USA) using a mobile phase of acetonitrile containing 0.1% formic acid and aqueous 5 mM ammonium acetate buffer containing 0.1% formic acid (80:20, v/v) at a flow rate 0.5ml/min. All of the analytes were detected in positive ion mode using multiple reactions monitoring (MRM). The MRM transitions were monitored at m/z 411.3>191.12, 427>206.97 and 313.0>256.03were used to quantify RIS, 9-OH- RIS and IS respectively. The calibration curves were obtained in the concentration of 0.2-500ng/mL for both RIS and its active metabolite 9-OH- RIS. All validation parameter were within the acceptable range described in FDA guideline for bioanalytical method validation.

This method developed is simple, rapid and was successfully applied for pharmacokinetics study of dose response curve of RIS in rats after oral administration at three different doses ranging from 0.3 to 6.0mg/kg.