Simultaneous Determination Of Fluoxetine Research Articles

FLUOKSETİN VE OLANZAPİNİN EŞ ZAMANLI SPEKTROFOTMETRİK TAYİNİ VE YEŞİL KİMYA UYGULAMALARI

Objective: In our study, the simultaneous determination of fluoxetine (FLX) and olanzapine (OLZ) was performed by absorbance subtraction and absorbance correction spectrophotometric methods. Material and Method: The active substances were determined by choosing the isosbestic point of 232 nm in the absorbance subtraction method and 255 nm and 245 nm wavelengths in the absorbance correction method. The accuracy of the methods was determined by applying the percentage recovery studies to the laboratory mixtures. The percent recovery values were found in the range of 98.1-100.2 for OLZ and 96.8-105.3 for FLX. The concentration range studied was 3.12-15.62 and 3.45-17.28 µg/ml for OLZ and FLX, respectively. Result and Discussion: In the study, two active substances used in antidepressant treatment were determined simultaneously. Today, these active substances used in the treatment have started to be used in combination in order to achieve a better effect of the treatment. Therefore, simultaneous analysis of two active substances becomes important. Two different spectrophotometric methods were used for analysis. The methods have been successfully applied and validated for the simultaneous determination of antidepressant active substances. Since the applied methods do not require pre-separation and can be applied directly, the amount of waste generated is reduced. Environmentally sensitive methods have been applied.

Simultaneous determination of fluoxetine, venlafaxine, vortioxetine and their active metabolites in human plasma by LC–MS/MS using one-step sample preparation procedure

The aim of antidepressant therapy is to induce remission and prevent relapses of major depressive disorder with minimum adverse effects during the treatment. Due to high variability in metabolism, therapeutic drug monitoring is recommended as a useful tool for individualisation of the therapy. For this purpose, we have developed simple and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for quantification of fluoxetine (FLX), venlafaxine (VEN), vortioxetine (VTX) and their active metabolites norfluoxetine (NFLX) and O-desmethylvenlafaxine (ODV). After one-step extraction procedure using OSTRO plate, analytes were separated by gradient elution on Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column with runtime 4.2 min. The detection was done on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode with transitions at m/z 310.23 → 148.20 for FLX, m/z 296.23 → 134.20 for NFLX, m/z 278.31 → 121.13 for VEN, m/z 264.31 → 107.14 for ODV and m/z 299.19 → 150.05 for VTX using a positive electrospray ionisation interface. The method was successfully validated according to the European Medicine Agency guideline for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability over a concentration range of 1–300 ng/mL for FLX, NFLX, VEN, ODV and 0.2–100 ng/mL VTX. Extraction recovery for each analyte was > 80 %, and no significant matrix effects were observed. The developed method was employed for quantification of antidepressants in clinical samples from patients treated with either FLX, VEN, or VTX.

Simultaneous Determination of Fluoxetine, Estrone, Pesticides, and Endocrine Disruptors in Wastewater by Gas Chromatography–Mass Spectrometry (GC–MS) Following Switchable Solvent–Liquid Phase Microextraction (SS–LPME)

A simple and sensitive analytical method for the determination of fluoxetine, estrone and selected pesticides and endocrine disruptors has been proposed for wastewater analysis by gas chromatography–mass spectrometry (GC–MS). A switchable solvent was produced with N,N-dimethylbenzylamine by changing its hydrophobic properties by the addition of CO2 for protonation. Sodium hydroxide was added to switch the solubility of the extraction solvent and to allow phase separation in the sample/standard medium. Analytical parameters affecting the extraction outputs such as volume of switchable solvent, concentration and volume of sodium hydroxide, mixing type and period were investigated to improve the extraction recovery of the selected analytes. Under the optimum conditions, limits of detection and limits of quantification for the analytes were calculated in the ranges of 0.16–8.6 ng mL−1 and 0.54–29 ng mL−1, respectively. The developed method was successfully applied to synthetic wastewater and two municipal wastewater samples. None of the selected analytes were detected in the samples. High recovery values demonstrated that the proposed method was reliable and applicable to complex matrices.

Simultaneous determination of fluoxetine and norfluoxetine enantiomers using isotope discrimination mass spectroscopy solution method and its application in the CYP2C9-mediated stereoselective interactions

In this study, we developed an LC–MS/MS method based on an isotope discrimination mass spectroscopy solution (IDMSS) technology to simultaneously quantify enantiomers of fluoxetine (FLX) and norfluoxetine (NFLX) in a CYP2C9 incubation mixture. S-FLX and S-NFLX were labeled to form S-FLX-d5 and S-NFLX-d5. The method has several advantages over conventional chiral separation methods, in terms of the analysis period, resolution, and lower limit of quantification. The primary advantage of the method is that the two enantiomers can always be simultaneously determined by mass spectroscopy regardless if they are separated on column or not, owing to which it has high throughput and high sensitivity. The lower limit of quantification (amount on column) is 12.5 and 1.25pg for FLX and NFLX, respectively. The retention time of FLX, NFLX, and the internal standard is only 1.9min. The calibration curves were linear over the concentration range of 0.1–100ng/ml for NFLX and 1–1000ng/ml for FLX with an accepted reproducible (RSD<10%) and accurate (CV<10%). No significant kinetic isotope effect was found in the metabolism of S-FLX-d5 catalyzed by CYP2C9*1 and CYP2C9*2. The half-maximal inhibitory concentration values between R-FLX and S-FLX catalyzed by CYP2C9*1 and CYP2C9*2 were determined in this study. The inhibitory effects of R- to S-FLX were stronger than those of S- to R-FLX in both CYP2C9*1 and CYP2C9*2. The IDMSS technology is useful for stereoselective study of chiral compound in vitro.

Sensitive and specific liquid chromatography-tandem mass spectrometry method for assay of fluoxetine and its metabolite norfluoxetine in human plasma and application of method to pharmacokinetic analysis

A simple, specific and sensitive high-performance liquid chromatography — electrospray tandem mass spectrometry method is developed for the simultaneous determination of fluoxetine and its metabolite norfluoxetine in human plasma. Plasma samples were simply treated with acetonitrile to precipitate and remove proteins and the isolated supernatants were directly injected into the high-performance liquid chromatography — electrospray tandem mass spectrometry system. Chromatographic separation of the analytes was achieved on a Discovery C18 (100 × 2.1 mm I.D., particle size 3.0 μm) column using 0.1% formic acid in water — acetonitrile (40: 60) as mobile phase with a flow rate of 0.2 mL/min. Diazepam was used as the internal standard. The compounds were ionized in the electrospray ionization source of the mass spectrometer and were detected by selected reaction ion monitoring of the transitions of m/z 310 → m/z 44.3 for fluoxetine, m/z 296 → m/z 134 for norfluoxetine and m/z 285 → m/z 193 for the internal standard. The method has low limit of detection (LOD) of 0.02 ng/mL and 0.03 ng/mL for fluoxetine and norfluoxetine, respectively. The inter- and intra-run precision was measured to be below 5.3% (relative standard deviation) for both fluoxetine and norfluoxetine. The developed method was successfully used to investigate plasma concentrations of fluoxetine and norfluoxetine in the pharmacokinetic study of Chinese volunteers who received fluoxetine orally.

Densitometric determination of impurities in pharmaceuticals. Part VIII. Simultaneous determination of fluoxetine and (1RS)-3-methylamino-1-phenylpropan-1-ol,N-methyl-3-phenylpropan-1-amine, and C-1 as drug impurities

A densitometric TLC method has been developed for identification and quantification of fluoxetine and its impurities — (1 RS )-3-methylamino-1-phenylpropan-1-ol, N -methyl-3-phenylpropan-1-amine, and C-1, the last of which has not previously been analyzed. The compounds were separated on silica gel 60 F 254 HPTLC plates, with chloroform-methanol-25% ammonia, 45 + 4.5 + 0.5 ( v/v ), as mobile phase. UV and visible densitometric scanning were performed at λ = 260 and 530 nm, respectively, after visualization of the chromatograms with ninhydrin solution. The method enables good separation of the constituents ( R F = 0.20, 0.41, 0.52, and 0.67) with sufficiently high detection limit and recovery for the individual constituents.

Issues in methodology and applications for therapeutic drug monitoring of fluoxetine and norfluoxetine enantiomers.

A standardization of the analytical procedures for monitoring of fluoxetine and norfluoxetine enantiomers is described. Simultaneous determination of fluoxetine and norfluoxetine enantiomers in plasma and serum was performed by high-performance liquid chromatography with a chiral stationary phase, using ultraviolet absorbance detection. The analytes were extracted from the biologic matrix by alkalinization with NaOH and solid-phase extraction. Stability studies were conducted in EDTA, lithium-heparinized plasma and in serum spiked with the analytes stored at +4 degrees C for 1 week and at -20 degrees C for 1 month. Furthermore, stability studies in NaOH and in the extraction solvents were executed. Using this methodology, EDTA plasma is the most suitable matrix for drug monitoring, even if the storage should not exceed 3 weeks at -20 degrees C. Furthermore, the biologic sample should be left in NaOH for a short time before solid-phase extraction to prevent a degradation of matrix, which would interfere with the chromatographic analysis.

Simultaneous determination of fluoxetine and norfluoxetine enantiomers in biological samples by gas chromatography with electron-capture detection

An electron-capture gas chromatographic procedure was developed for the simultaneous analysis of the enantiomers of fluoxetine and norfluoxetine. The assay involves basic extraction of these enantiomers from the biological samples, followed by their conversion to diastereoisomers using the chiral derivatizing reagent ( S)-(−)-N-trifluoroacetylprolyl chloride. The method was utilized to detect and measure the quantity of these enantiomers in plasma and urine of patients and in liver and brain tissue of rats treated with ( R,S)-fluoxetine.

Determination of Fluoxetine and Norfluoxetine in Serum by Liquid Chromatography with Fluorescence Detection

Abstract A reversed phase liquid chromatographic procedure with fluorescence detection for the simultaneous determination of fluoxetine and its active metabolite, norfluoxetine in human serum is described. A 0.5-mL aliquot of the sample after the addition of protriptyline as the internal standard is passed through a 1-mL BondElut C18 silica extraction column. The column is selectively washed to remove polar, neutral, acidic and weakly basic compounds. The desired compounds are eluted with a 0.25-mL aliquot of a mixture of 0.1 N perchloric acid + acetonitrile (1:3). A 20-uL aliquot of the eluate is injected onto a 15 cm × 4.6 mm (i.d.) column packed with 5-um C8-silica particles, which is eluted at ambient temperature with a mobile phase containing tetramethyl-ammonium perchlorate. The peaks are detected with a fluorescence detector (ex = 235 nm; em = 310 nm). In the resulting chromatogram, there are only few extraneous peaks, fluoxetines give sharp peaks which are well resolved from peaks for solvent and ...