Simultaneous determination of fluoxetine and its major active metabolite norfluoxetine in human plasma by LC‐MS/MS using supported liquid extraction

Liu, Yu; Emm, Thomas; Yeleswaram, Swamy

doi:10.1002/bmc.1597

Cited by 27 publications

(9 citation statements)

References 12 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fluoxetine and norfluoxetine liquid chromatography mass spectrometry (LC/MS-MS) assays (Chu and Metcalfe 2007; Li et al 2011) were adapted for monkeys. Extraction used Biotage Isolate SLE200 system.…”

Section: Methodsmentioning

confidence: 99%

Fluoxetine: juvenile pharmacokinetics in a nonhuman primate model

Golub

Hogrefe

2014

Psychopharmacology

View full text Add to dashboard Cite

Rationale-The selective serotonin reuptake inhibitor (SSRI) fluoxetine is the only psychopharmacological agent approved for use in children. While short-term studies of side effects have been performed, long-term consequences for brain development are not known. Such studies can be performed in appropriate animal models if doses modeling therapeutic use in children are known.Objectives-To identify a daily dose of fluoxetine in juvenile monkeys which would result in serum fluoxetine and norfluoxetine concentrations in the therapeutic range for children.Methods-Juvenile (2.5 year old rhesus monkeys, n=6) received single administration of doses of 1, 2 and 4 mg/kg-d fluoxetine on a background of chronic dosing at an intermediate level to provide steady state conditions to model therapeutic administration. Using nonlinear modeling, standard pharmacokinetic parameters were derived. Cerebrospinal fluid monoamine neurotransmitters were assayed to confirm the pharmacological effects.Results-Dose-dependent AUC and Cmax values were seen while Tmax and absorption/ elimination half-lives were minimally influenced by dose. A dosage of 2 mg/kg-d given over a 14 week period led to steady state serum concentrations of active agent (fluoxetine + norfluoxetine) similar to those recorded from drug monitoring studies in children. Cisternal cerebrospinal fluid concentrations of serotonin increased significantly over the 14 week period, while concentrations of the serotonin metabolite (5-HIAA) were lower but not significantly different.Conclusions-2 mg/kg/d fluoxetine in juvenile rhesus monkeys provides an internal dose similar to therapeutic use in children and will help establish a valuable animal model for understanding fluoxetine therapeutic and potential adverse effects in children.

show abstract

Section: Methodsmentioning

confidence: 99%

Fluoxetine: juvenile pharmacokinetics in a nonhuman primate model

Golub

Hogrefe

2014

Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…After oral administration, FLU is readily absorbed from the gastrointestinal tract with peak blood concentration appearing after 6–8 h. As the active metabolite of FLU, norfluoxetine (NFLU, Figure 1d), contributes to the long elimination half‐life ( t 1/2 , 3–15 days) and the overall clinical effect of FLU. Several bioanalytical methods have been reported for the simultaneous determination of FLU and NFLU in biological fluids (Chow, Szeitz, Rurak, & Riggs, 2011; Chu & Metcalfe, 2007; Crifasi, Le, & Long, 1997; da Silva et al, 2018; Deglon, Lauer, Thomas, Mangin, & Staub, 2010; Djordjevic, Kovacevic, Miljkovic, Vuksanovic, & Pokrajac, 2005; Franceschi, Faggiani, & Furlanut, 2009; Guo, Li, Wang, & Chen, 2006; Houbart et al, 2012; Kovacevic, Pokrajac, Miljkovic, Jovanovic, & Prostran, 2006; Li, Emm, & Yeleswaram, 2011; Mifsud & Sghendo, 2012; Ni et al, 2018; Oliveira, de Figueiredo, & Dos Santos‐Neto, 2013; Souverain, Mottaz, Cherkaoui, & Veuthey, 2003; Sutherland et al, 2001). Recently, a sensitive and simple UHPLC–MS/MS method for simultaneous quantification of VOR and FLU in human plasma has been developed and validated (Kertys et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous quantification of vortioxetine, fluoxetine and their metabolites in rat plasma by UPLC–MS/MS

Wang

Chen

et al. 2020

Biomedical Chromatography

View full text Add to dashboard Cite

In this study, a specific and quick ultra‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was fully developed and validated for simultaneous measurement of the rat plasma levels of vortioxetine (VOR), Lu AA34443 (the major metabolite of VOR), fluoxetine and its metabolite norfluoxetine with diazepam as the internal standard (IS). After a simple protein precipitation with acetonitrile for sample preparation, the separation of the analytes were performed on an Acquity UPLC BEH C18 (2.1 × 50 mm, 1.7 μm) column, with acetonitrile and 0.1% formic acid in water as mobile phase by gradient elution. The detection was achieved on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode via an electrospray ionization source. Good linearity was observed in the calibration curve for each analyte. The data of precision, accuracy, matrix effect, recovery and stability all conformed to the bioanalytical method validation of acceptance criteria of US Food and Drug Administration recommendations. The newly developed UPLC–MS/MS method allowed simultaneous quantification of VOR, fluoxetine and their metabolites for the first time and was successfully applied to a pharmacokinetic study in rats.

show abstract

“…Thus, the rate of fluoxetine elimination is fairly slow, with a half‐life of 47–72 h . Several analytical methods have been reported for determining the levels of only fluoxetine or fluoxetine and its active metabolite, norfluoxetine, in biological fluids for therapeutic drug monitoring and bioavailability studies .…”

Section: Introductionmentioning

confidence: 99%

Indirect enantioseparation of fluoxetine in mouse serum by derivatization with 1R‐(–)‐menthyl chloroformate followed by ultra high performance liquid chromatography and quadrupole time‐of‐flight mass spectrometry

Zhao

Jin

Shin

et al. 2016

J of Separation Science

View full text Add to dashboard Cite

Here we describe a simple and sensitive analytical method for the enantioselective quantification of fluoxetine in mouse serum using ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The sample preparation method included a simple deproteinization with acetonitrile in 50 μL of serum, followed by derivatization of the extracts in 50 μL of 2 mM 1R-(-)-menthyl chloroformate at 45ºC for 55 min. These conditions were statistically optimized through response surface methodology using a central composite design. Under the optimized conditions, neither racemization nor kinetic resolution occurred. The derivatized diastereomers were readily resolved on a conventional sub-2 μm C18 column under a simple gradient elution of aqueous methanol containing 0.1% formic acid. The established method was validated and found to be linear, precise, and accurate over the concentration range of 5.0-1000.0 ng/mL for both R and S enantiomers (r(2) > 0.993). Stability tests of the prepared samples at three different concentration levels showed that the R- and S-fluoxetine derivatives were relatively stable for 48 h. No significant matrix effects were observed. Last, the developed method was successfully used for enantiomeric analysis of real serum samples collected at a number of time points from mice administered with racemic fluoxetine.

show abstract

Simultaneous determination of fluoxetine and its major active metabolite norfluoxetine in human plasma by LC‐MS/MS using supported liquid extraction

Cited by 27 publications

References 12 publications

Fluoxetine: juvenile pharmacokinetics in a nonhuman primate model

Fluoxetine: juvenile pharmacokinetics in a nonhuman primate model

Simultaneous quantification of vortioxetine, fluoxetine and their metabolites in rat plasma by UPLC–MS/MS

Indirect enantioseparation of fluoxetine in mouse serum by derivatization with 1R‐(–)‐menthyl chloroformate followed by ultra high performance liquid chromatography and quadrupole time‐of‐flight mass spectrometry

Contact Info

Product

Resources

About