UPLC-Tandem Mass Spectrometry Method for Simultaneous Determination of Fluoxetine, Risperidone, and Its Active Metabolite 9-Hydroxyrisperidone in Plasma: Application to Pharmacokinetics Study in Rats.

Essam Ezzeldin,Nisreen F Abo-Talib,Marwa H Tammam

doi:10.1155/2017/5187084

Abstract

Risperidone (RIS) is used as an antipsychotic drug alone or with other drugs, like fluoxetine (FLX). A simple method was developed and validated for the determination of both RIS and its metabolite 9-hydroxyrisperidone (9-OH-RIS), FLX, and olanzapine (OLA) as an internal standard in rat's plasma using UPLC-MS/MS. FLX, RIS, 9-OH-RIS, and OLA were purified using acetonitrile as a protein precipitating agent. Separation was performed on an ACQUITY™ “UPLC BEH™” C18 column (50 mm × 2.1 mm i.d., 1.7 μm; Waters Corp., USA). The ranges of the calibration curves were 1.0–1000.0 ng/mL for FLX and 0.2–1000.0 ng/mL for RIS and 9-OH-RIS. Linearity, recovery, precision, and stability were within the acceptable range. This method is rapid, fast, and precise for the determination of RIS and FLX in plasma and is applicable in pharmacokinetic studies.

Highlights

Fluoxetine (FLX), which has the full formula (3RS)-Nmethyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1amine hydrochloride (Figure 1), is a selective serotonin reuptake inhibitor antidepressant drug [1] with comparable effects to those of tricyclic antidepressants [2]
There is no reported method for the determination of FLX and RIS and 9-OH-RIS in plasma simultaneously; the aim of this study was to develop and validate a simple, fast, and specific UPLC-mass spectrometry (MS)/MS assay method for simultaneous extraction, separation, and quantification of the cited drugs
A consistent, selective, and specific and fully validated UHPLC-MS/MS method was developed for the determination of FLX, RIS, and 9-OH-RIS in rat plasma

Summary

Introduction

Fluoxetine (FLX), which has the full formula (3RS)-Nmethyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1amine hydrochloride (Figure 1), is a selective serotonin reuptake inhibitor antidepressant drug [1] with comparable effects to those of tricyclic antidepressants [2]. Maximum FLX plasma concentration is reached 6–8 h after oral administration. FLX has fewer cardiovascular and anticholinergic side effects than comparable drugs [2]. Risperidone (RIS), which has the full formula (3-[2-[4(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one) (Figure 1), is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychoses. It is more effective and produces fewer side effects than typical antipsychotics [4].

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