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International Journal of Analytical Chemistry
Volume 2017, Article ID 1271383, 11 pages
https://doi.org/10.1155/2017/1271383
Research Article

New Modified UPLC/Tandem Mass Spectrometry Method for Determination of Risperidone and Its Active Metabolite 9-Hydroxyrisperidone in Plasma: Application to Dose-Dependent Pharmacokinetic Study in Sprague-Dawley Rats

1Pharmaceutical Chemistry Department and Drug Bioavailability Laboratory, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
2Drug Bioavailability Center, National Organization for Drug Control and Research, P.O. Box 29, Cairo, Egypt

Correspondence should be addressed to Marwa Tammam; moc.liamg@awram.mammat

Received 4 January 2017; Revised 28 February 2017; Accepted 16 March 2017; Published 3 May 2017

Academic Editor: David M. Lubman

Copyright © 2017 Essam Ezzeldin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sensitive and specific liquid-chromatography tandem mass spectrometry (UPLC-MS/MS) assay has been developed and validated for simultaneous quantification of risperidone (RIS) and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in rat plasma using olanzapine (OLA) as internal standard (IS). Pharmacokinetics of risperidone and its active metabolite 9-hydroxyrisperidone was compared across different doses (0.3, 1.0, and 6.0 mg/kg). Serial blood sample was collected over a time of 48 hours and analyzed for risperidone and its active metabolite 9-hydroxyrisperidone. The pharmacokinetics parameters including , , and AUC were determined for risperidone and its active ingredient. The method was linear in the concentration range of 0.2–500 ng/mL for risperidone and 9-OH-risperidone, with coefficients of determination greater than 0.998 and lower limit of quantitation of 0.2 ng/mL. Blood levels of risperidone and its active metabolite were roughly dose-proportional. The method developed herein is simple and rapid and was successfully applied for dose-dependent pharmacokinetic study.