Determination Of Fluvoxamine Research Articles

New approach for stability study and determination of fluvoxamine in raw materials and pharmaceuticals through condensation with 2,2-dihydroxyindane-1,3-dione.

The present study describes the validation of a selective spectroscopic method for assay of fluvoxamine maleate (FXM). The validated method relies on condensation of FXM with 2,2-dihydroxyindane-1,3-dione and phenylacetaldehyde using Teorell-Stenhagen buffer (pH 6.6) to give coloured fluorescent product measured at 482 nm using 386 nm as the excitation wavelength. The parameters influencing the reaction were studied precisely and adjusted accurately. The constructed calibration graph appeared rectilinear over the following range (0.8-14 μg ml-1 ) and the estimated limit of detection was 0.25 μg ml-1 . Two pharmaceutical products from the Egyptian market were assayed using the suggested method and the final results agreed with measurements from other reported methods. Moreover, the drug was subjected to diverse stress conditions including acidic, alkaline, thermal, and photolytic degradation to examine the FXM stability. Directives from the International Conference on Harmonisation guidelines were applied to establish the validity of the work.

Determination of three antidepressants in urine using simultaneous derivatization and temperature-assisted dispersive liquid-liquid microextraction followed by gas chromatography-flame ionization detection.

This paper presents a fast and simple method for the extraction, preconcentration and determination of fluvoxamine, nortriptyline and maprotiline in urine using simultaneous derivatization and temperature-assisted dispersive liquid-liquid microextraction (TA-DLLME) followed by gas chromatography-flame ionization detection (GC-FID). An appropriate mixture of dimethylformamide (disperser solvent), 1,1,2,2-tetrachloroethane (extraction solvent) and acetic anhydride (derivatization agent) was rapidly injected into the heated sample. Then the solution was cooled to room temperature and cloudy solution formed was centrifuged. Finally a portion of the sedimented phase was injected into the GC-FID. The effect of several factors affecting the performance of the method, including the selection of suitable extraction and disperser solvents and their volumes, volume of derivatization agent, temperature, salt addition, pH and centrifugation time and speed were investigated and optimized. Figures of merit of the proposed method, such as linearity (r(2) > 0.993), enrichment factors (820-1070), limits of detection (2-4 ng mL(-1)) and quantification (8-12 ng mL(-1)), and relative standard deviations (3-6%) for both intraday and interday precisions (concentration = 50 ng mL(-1)) were satisfactory for determination of the selected antidepressants. Finally the method was successfully applied to determine the target pharmaceuticals in urine.

Synthesis and characterization of poly[N-isopropylacrylamide-co-1-(N,N-bis-carboxymethyl)amino-3-allylglycerol] grafted to magnetic nano-particles for the extraction and determination of fluvoxamine in biological and pharmaceutical samples

In this research, a novel method is reported for the surface grafting of N-isopropylacrylamide as a thermosensitive agent and 1-(N,N-bis-carboxymethyl)amino-3-allylglycerol with an affinity toward fluvoxamine onto magnetic nano-particles modified by 3-mercaptopropyltrimethoxysilane. The grafted nano-particles were characterized by Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analysis. The surface morphology was studied with scanning electron microscopy and transmission electron microscopy. The resulting grafted nano-particles were used in solid phase extraction and determining of trace fluvoxamine in biological human fluids and pharmaceutical samples. The profile of the fluvoxamine uptake by the modified magnetic nano-particles indicated good accessibility of the active sites in the grafted copolymer. It was found that the adsorption behavior could be fitted by the Freundlich adsorption isotherm model. It was observed that a maximum amount of fluvoxamine was released at a temperature above the lower critical solution temperature of the polymer.

Validated high-performance thin-layer chromatographic method for quantitation of fluvoxamine in the presence of degradation products formed under ICH recommended stress conditions

This paper describes a sensitive, selective, precise, and stability-indicating high-performance thin-layer chromatographic method for the determination of fluvoxamine as a bulk drug and in formulation. The method uses aluminium plates precoated with silica gel 60F-254 as the stationary phase and solvent system ethyl acetatetoluene-methanol-ammonia 7:2:1:0.5 (v/v/v/v). Fluvoxamine was subjected to acid and alkali hydrolysis, oxidation, and photodegradation. The peaks of the degradation products were well resolved from that of the pure drug and had significantly different RF values. The linear regression analysis data for the calibration plots showed a good linear relationship over a concentration range of 100–1000 ng spot−1. The mean values of the correlation coefficient, slope, and intercept were 0.9992 ± 0.02, 9.8493 ± 0.347, and 386.8 ± 0.71, respectively. Statistical analysis showed that the method is repeatable, selective and can separate the drug from its degradation products and can be used to monit...

Simultaneous Determination of Fluvoxamine and Its Metabolites in Human Liver Microsomes by High‐Performance Liquid Chromatography with Solid‐Phase Extraction

A simple and sensitive high‐performance liquid chromatography method was developed for the simultaneous quantitative determination of fluvoxamine and its two metabolites, fluvoxamino alcohol and fluvoxamino acid, in human liver microsomes. Chromatographic separation was achieved with a Grand‐pak C4‐5 column using a mobile phase at pH 2.5 of 0.5% KH2PO4‐acetonitrile (75:25, v/v). Analysis involved a solid‐phase extraction with an Oasis HLB cartridge, which gave high extraction recovery (>92.8%) with good selectivity. The lower limit of quantification of this assay was 78.6 nM for fluvoxamine and fluvoxamino acid, and 82.2 nM for fluvoxamino alcohol, respectively. The coefficient of variation of intra‐ and interday assays was less than 5.8% and accuracy was within 5.3% for all analytes (concentration range 78.6 nM–2.36 µM for fluvoxamine and fluvoxamino acid, and 82.2 nM–2.47 µM for fluvoxamino alcohol, respectively). This method is applicable for accurate and simultaneous determination of oxidative metabolites of fluvoxamine by human liver microsomes.

Determination and Validation of an LC Method for Fluvoxamine in Tablets

A new, simple, rapid and specific reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated for the determination of fluvoxamine in pharmaceutical dosage forms. The HPLC separation was achieved on a C18 μ-Bondapack column (250 mm × 4.6 mm) using a mobile phase of acetonitrile–water (80:20, v/v) at a flow rate of 1 mL min−1. Proposed method is based on the derivatization of fluvoxamine with 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) in borate buffer of pH 8.5 to yield a orange product. The HPLC method is based on measurement of the derivatized product using UV-visible absorbance detection at 450 nm. The method was validated for specificity, linearity, precision, accuracy, robustness. The degree of linearity of the calibration curves, the percent recoveries of fluvoxamine, the limit of detection and quantification, for the HPLC method were determined. The assay was linear over the concentration range of 45–145 ng mL−1 (r = 0.9999). Limit of detection and quantification for fluvoxamine were 15 and 50 ng mL−1, respectively. The results of the developed procedure (proposed method) for fluvoxamine content in tablets were compared with those by the official method. The method was found to be simple, specific, precise, accurate, reproducible and robust.

Determination of fluvoxamine in rat plasma by HPLC with pre-column derivatization and fluorescence detection using 4-fluoro-7-nitro-2,1,3-benzoxadiazole

A sensitive, simple and reliable method using high-performance liquid chromatographic (HPLC) assay of fluvoxamine (FLU), a selective serotonin reuptake inhibitor (SSRI), in rat plasma after pre-column derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) was developed in this study. Extracted plasma samples were mixed with NBD-F at 60 degrees C for 5 min and injected into HPLC. Retention times of FLU and an internal standard (propafenone) derivative were 15.5 and 13.5 min, respectively. The calibration curve was linear over the range 0.015-1.5 microg/mL (r2 = 0.9985) and the lower limits of detection and quantification of FLU were 0.008 and 0.015 microg/mL, respectively, in 100 microL of plasma. The derivative sample was stable at 4 degrees C for 1 day. The coefficients of variation for intra-day and inter-day assay of FLU were less than 8.3 and 9.6%, respectively. Other SSRIs and centrally acting drugs did not interfere with the peak of the FLU derivative. The method was applied for analysis of the plasma samples from rats treated with FLU. These results indicate that the method presented is useful to determine the FLU levels in rat plasma of volumes as small as 100 microL and can be applied to pharmacokinetic studies.

Determination of fluvoxamine and moclobemide in tablets by densitometric and videodensitometric TLC

New, simple, rapid, and accurate thin-layer chromatographic methods have been established for determination of fluvoxamine and moclobemide in tablets. The drugs were chromatographed on silica gel 60 F 254 plates in horizontal chambers with benzene-acetone-ethanol-25% aqueous ammonia, 9 + 7 + 2 + 1 ( v/v ), as mobile phase. Densitometric detection and quantification were performed at λ = 249 nm and λ = 236 nm, respectively, for fluvoxamine and moclobe-mide; videodensitometric detection was performed at λ = 254 nm for both drugs. The range of linearity was 1–10 μg per spot for fluvoxamine and moclobemide for both methods. The relative standard deviation for determination of these antidepressants in pharmaceuticals was less than 2.5% for densitometry and less than 5.1% for videodensitometry. Recovery of fluvoxamine from tablets was 101.20% by use of densitometry and 98.96% by use of videodensitometry; recovery of moclobemide from tablets was 101.15% and 98.81% respectively.

SPECTROPHOTOMETRIC DETERMINATION OF FLUVOXAMINE MALEATE AND FLUOXETINE HYDROCHLORIDE

Fluvoxamine maleate and fluoxetine hydrochloride react with eriochrome cyanine R and form pink ion-association compounds. These compounds are insoluble in water, but fairly soluble in organic solvents. Addition of methylcellulose affects the solubility of the compounds and increases the absorbance of the solution. Optimal reaction conditions have been established, and a new spectrophotometric method has been developed for the determination of fluvoxamine and fluoxetine in the concentration ranges 0.6–15 and 0.3–5.0 μg/cm3, respectively.

Determination of Fluvoxamine and Paroxetine in Human Serum with High-Performance Liquid Chromatography and Ultraviolet Detection

We optimized an isocratic reversed phase high performance liquid chromatography with ultraviolet detection to quantify, simultaneously, the selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and paroxetine in human serum. Fluvoxamine was used as the internal standard for the determination of paroxetine, and paroxetine served as internal standard for the fluvoxamine assay. The method involved a pre-column technique for the on-line liquid-solid extraction with direct injection of serum samples and for their pre-concentration. Automation was achieved by column switching. The chromatographic separation was performed on an Ultrasep ES 100 CN-column with acetonitrile/methanol/phosphate buffer (58/19/23, v/v/v) as mobile phase. A linear relationship (r2 > 0.99) was noted between the concentrations of fluvoxamine or paroxetine and the detector signal. The lower limits of detection in human serum of fluvoxamine and paroxetine were 5 and 2 μg/L, respectively. The accuracy of the quality control samples deviated by m± 8% with a within-day and between-day precision of less than 12.1%, and 10.5% for fluvoxamine and paroxetine, respectively. The method is presently being applied in our clinic for the routine therapeutic drug monitoring of both SSRIs.

High performance liquid chromatography with ultraviolet detection used for laboratory routine determination of fluvoxamine in human plasma

Fluvoxamine is an antidepressant drug introduced into the clinic in 1986. It acts by selectively inhibiting neuronal serotonin recapture. It can be quantified by several methods, including high performance liquid chromatography. The HPLC method used so far needs special equipment and has poor sensitivity. The technique is difficult and time consuming. An easier, quicker and more sensitive HPLC assay for the routine determination of fluvoxamine in human plasma has therefore been developed. After alkalinisation and direct extraction by a mixture of n-hexane-isoamylic alcohol 985: 15 (v/v) of plasma samples, the organic phases were further extracted by HCl 0.1 N. Thirty microL of the final extract (with loxapine as internal standard) were injected directly into a C-8 column with a mobile phase consisting of 370 mL acetonitrile, 0.4 mL diethylamine, 630 mL of distilled water, 25 mL pic B5. UV detection at 254 nm was used. The whole process was completed in 40 min. The detection limit was 10 ng mL-1. No interference was found either with several benzodiazepines or with antidepressant drugs commonly associated during treatments.

Determination of fluvoxamine in human plasma by high-performance liquid chromatography with fluorescence detection

Fluvoxamine and nortriptyline, the assay internal standard, were extracted from plasma with ethyl acetate, then reacted with dansyl chloride. The derivatives were quantitated by isocratic reversed-phase high-performance liquid chromatography with fluorescence detection. The assay calibration range for fluvoxamine was 10–1000 ng/ml using a 1-ml plasma sample. Pooled plasma quality control sample relative recoveries at 25 and 250 ng/ml were 103 and 105%, respectively. Estimates of quality control inter-day precision during validation were ≤3% relative standard deviation. The assay was cross-validated with a gas chromatographic method and has been employed in therapeutic drug level monitoring.

Sensitive one-step extraction procedure for column liquid chromatographic determination of fluvoxamine in human and rat plasma

A normal-phase column liquid chromatographic assay for fluvoxamine, a recently introduced atypical antidepressant, has been developed. Prior to analysis, aliquots of alkalinized plasma were extracted with n-hexane. These extracts were then injected into a 5-microns Resolve spherical silica column. Fluvoxamine and the internal standard, clovoxamine, were detected at a wavelength of 254 nm. Standard curves were linear over the concentration range 2-400 ng/ml. Acceptable coefficients of variation were obtained for both within-run and day-to-day studies. The estimated limit of detection is 0.5 ng/ml, and selected drugs checked for coadministration show no analytical interference. This assay was used to evaluate the pharmacokinetics of fluvoxamine in rats.

High performance liquid chromatographic determination of fluvoxamine in human plasma

A method has been developed for the separation and measurement of fluvoxamine in human plasma by high performance liquid chromatography. The method uses metapramine as an internal standard and provides a limit of detection of about 1.5 ng/mL for fluvoxamine. At a concentration of 25 ng/mL, fluvoxamine could be measured within a coefficient of variation of +/- 5.82 of the mean and at 100 ng/mL within a CV of +/- 2.78 of the mean. The method has been applied to the analysis of plasma from patients undergoing fluvoxamine therapy.

Determination of fluvoxamine in human plasma by high-performance liquid chromatography with ultraviolet detection

Determination of fluvoxamine in human plasma by high-performance liquid chromatography with ultraviolet detection