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IJPER · Lens · In vitro Metabolism of Risperidone on Isolated Microsomes of Rat Liver: Metabolite Identification and Profiling by RP-HPLC and LC-MS Techniques

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Article · Volume 53, Issue 2S · pp. s179–s185

In vitro Metabolism of Risperidone on Isolated Microsomes of Rat Liver: Metabolite Identification and Profiling by RP-HPLC and LC-MS Techniques

Prutha Shirodkar1, Harshal Chavan2, Rajendra Mogal3, Avinash Dhake1

  1. 1Department of Pharmaceutical Chemistry, S.M.B.T. College of Pharmacy, Nashik, Maharashtra, INDIA.
  2. 2Department of Pharmaceutical Chemistry, Sandip Foundation’s, Sandip Institute of Pharmaceutical Sciences, Nashik, Maharashtra.
  3. 3Department of Pharmaceutics, Sandip Foundation’s, Sandip Institute of Pharmaceutical Sciences, Nashik, Maharashtra, INDIA.

Abstract

Objective: The objective of present research work is to study in vitro metabolism of risperidone on isolated microsomes of rat liver.Methods: Its biotransformation was examined using isolated microsomes derived from rat livers. Their separation was accomplished on Jasco RP-HPLC C-18 column (250mm x 4.6mm x 5µm) using methanol: 50mM Potassium dihydrogen phosphate (50:50 %v/v) mobile phase, detected at a wavelength of 280nm.Results: In vitro metabolism of RIS was investigated using the cytochrome P450 (CYP450) enzymes supplemented with an NADPH- generating system. Incubation of RIS with rat liver microsomes resulted in the formation of 2 major hydroxy metabolites.Conclusion: Formation of all the metabolites is correlated with Phase I biotransformation CYP enzyme subfamilies. The method was extended to LC-MS for further characterization of the metabolites using standards and the probable metabolites were proposed.

Keywords: RIS; Microsomes; Cytochrome P450; Biotransformation; LC-MS

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