Development and validation of liquid chromatography/tandem mass spectrometry analysis for therapeutic drug monitoring of risperidone and 9-hydroxyrisperidone in pediatric patients with autism spectrum disorders

Abstract

Objectives The sensitive, accurate and specific LC-MS/MS method, which a small-volume injection has been developed and validated for simultaneous quantification of RIS and 9-OH-RIS plasma concentrations in ASD pediatric patients. Methods Plasma samples were extracted by using the protein precipitation extraction technique and were separated on an Agilent, USA C18 column (4.6cm×50mm; 1.8 μm particle size). Detection was by MS-MS with an analytical run time of 6minutes. Results The recoveries were in the range of 95.01-112.62% for RIS and 90.27-114.00% for 9-OH-RIS. The method was applied in the therapeutic drug monitoring (TDM) of ASD pediatric patients treated with oral RIS. This study was to investigate the relationship between RIS dosages with RIS plasma levels including to investigate the correlations between RIS plasma levels and serum prolactin levels in ASD pediatric patients. Risperidone doses were significantly positively related with the concentration of RIS, 9-OH-RIS and active moiety. Moreover, the result indicates that the higher concentrations of RIS and its metabolite have a tendency to produce prolactin elevations than the lower RIS concentrations. Conclusion The determination of RIS and its metabolites in individual patient could be clinically useful for prediction and monitoring of treatment response to RIS. Therefore, we recommend the determination of RIS and its metabolites as part of an ongoing study in which routinely monitored for compliance and to adjust the RIS dose to achieve the optimum clinical outcome as well as to aware of the adverse drug reaction.