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. 2017:2017:5187084.
doi: 10.1155/2017/5187084. Epub 2017 Jun 1.

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  1   2 , Nisreen F Abo-Talib  2 , Marwa H Tammam  2
Affiliations

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 et al. J Anal Methods Chem. 2017.

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.

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Figures

Figure 1
Figure 1
Chemical structure of fluoxetine, risperidone, 9-OH-risperidone, and olanzapine.
Figure 2
Figure 2
Full scan positive ion mass spectra and the proposed fragmentation of (a) FLX, (b) RIS, (c) 9-OH-RIS, and (d) OLA (IS).
Figure 3
Figure 3
MRM chromatogram for FLX, RIS, and 9-OH-RIS and the IS (OLA) resulting from analysis of blank plasma.
Figure 4
Figure 4
MRM chromatogram of plasma spiked with 100.0 ng/mL of FLX, RIS, and 9-OH-RIS and 1200.0 ng/mL of the IS (OLA).
Figure 5
Figure 5
Standard calibration curves of (a) FLX, (b) RIS, and (c) 9-OH-RIS.
Figure 6
Figure 6
MRM chromatogram of plasma sample from a rat at 1 hr after administration of oral dosing of 10 mg/kg of FLX and 0.3 mg/kg of RIS.
Figure 7
Figure 7
Mean plasma concentration-time profiles after a single oral dose of 10 mg/kg of FLX and 0.3 mg/kg of RIS.
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