Spectrophotometric determination of certain antidepressants in pharmaceutical preparations.

Simple and reproducible spectrophotometric methods have been developed for determination of sertraline, fluoxetine, and venlafaxine in pharmaceutical preparations. The methods are based on the reactions between the studied drug substances and ion-pair agents (bromothymol blue, bromocresol green, or bromophenol blue) to produce yellow-colored ion-pair complexes in acidic buffers. After extracting in chloroform, the ion-pair complexes are spectrophotometrically determined at the optimum wavelength. Optimizations of the reaction conditions were carried out. Beer's law was obeyed within the concentration range from 1 to 15 microg/mL. The molar absorptivity, Sandell sensitivity, and detection and quantification limits were also determined. The developed methods were applied successfully for the determination of these drugs in some available commercial preparations. The results were compared statistically with those obtained from reported high-performance liquid chromatography methods.

A sensitive HPLC method for the determination of fluoxetine and norfluoxetine in human plasma with fluorescence detection.

A selective, sensitive, and precise HPLC method for the simultaneous determination of fluoxetine (FL) and its N-demethylated metabolite norfluoxetine (NFL) in human plasma has been developed. Following extraction with n-hexane, FL, NFL, and fluvoxamine (internal standard) were derivatized with 7-chloro-4-nitrobenzofurazan (NBD-Cl) under weakly alkaline conditions. NBD derivatives were extracted with chloroform after acidification and chromatographed on a reversed-phase column with gradient elution using acetonitrile and 0.1 mol/L nitric acid (pH 3) solution. Calibration curves were linear over the range of 1.0-100.0 ng/mL and 0.1-50.0 ng/mL for FL and NFL, respectively, with inter- and intraassay precision given by a relative standard deviation (RSD%) of less than 9.2%. The lower limits of quantification were 1.0 ng/mL for FL and 0.1 ng/mL for NFL. Recoveries of FL and NFL from plasma at three different concentrations were assessed. Average recovery was about 100% for both substances. The assay was applied to pharmacokinetic study in 2 healthy volunteers after a single oral administration of 40 mg of FL.

An HPLC method for the determination of atorvastatin and its impurities in bulk drug and tablets.

A simple high-performance liquid chromatographic (HPLC) method was developed for the analysis of atorvastatin (AT) and its impurities in bulk drug and tablets. This method has shown good resolution for AT, desfluoro-atorvastatin (DFAT), diastereomer-atorvastatin (DSAT), unknown impurities and formulation excipients of tablets. A gradient reverse-phase HPLC assay was used with UV detection. Some solvent systems prepared using methanol or acetonitrile and water or buffer systems with different pH values were tested. Capacity factors of related substances were calculated at all tested systems. Best resolution has been determined using a Luna C18 column with acetonitrile-ammonium acetate buffer pH 4-tetrahydrofuran (THF) as mobile phase. Samples were eluted gradiently with the mobile phase at flowrate 1.0 ml min(-1) and detected at 248 nm. The proposed method was applied to the determination of impurities and were found to contain 0.057-0.081, 0.072-0.097, 0.608-0.664% of the DFAT, DSAT and total impurity, respectively.

Simultaneous determination of moexipril hydrochloride and hydrochlorothiazide in tablets by derivative spectrophotometric and high-performance liquid chromatographic methods.

Two new simple and selective assay methods have been presented for the binary mixtures of moexipril hydrochloride (MOEX) and hydrochlorothiazide (HCTZ) in pharmaceutical formulations. The first method depends on second-derivative ultraviolet spectrophotometry with zero-crossing measurements at 215 and 234 nm for MOEX and HCTZ, respectively. The assay was linear over the concentration ranges 1.0-11.0 microg ml(-1) for MOEX and 0.5-9.0 microg ml(-1) for HCTZ. The determination limits for MOEX and HCTZ were found to be 1.0 and 0.5 microg ml(-1), respectively; while the detection limits were 0.2 microg ml(-1) for MOEX and 0.1 microg ml(-1) for HCTZ. The second method was based on isocratic reversed-phase liquid chromatography by using a mobile phase acetonitrile-20 mM phosphate buffer (pH 4.0) (50:50, v/v). Lisinopril was used as an internal standard (IS) and the substances were detected at 212 nm. The linearity range for both drugs was 0.5-12.0 microg ml(-1). The determination and detection limits were found to be 0.100 and 0.010 microg ml(-1) for MOEX and 0.025 and 0.005 microg ml(-1) for HCTZ, respectively. The proposed methods were successfully applied to the determination of these drugs in synthetic mixtures and commercially available tablets with a high percentage recovery, good accuracy and precision.

Analytical methods for the quantitative determination of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in biological samples.

Published analytical methods for the quantitative determinations of presently available five 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins"), lovastatin, simvastatin, pravastatin, fluvastatin and atorvastatin, are reviewed for therapeutic drug monitoring purpose in patients. Almost all assay reviewed are based on high-performance liquid chromatography or gas chromatography. Some purification steps (liquid-liquid extraction, solid-phase extraction, etc.) have been used before they are submitted to separation by chromatographic procedures and they are detected by various detection methods like UV, fluorescence and mass spectrometry. This review shows that most method may be used quantitative determination of statins in plasma and they are suitable for therapeutic drug monitoring purpose of these drugs.

Spectrofluorimetric and spectrophotometric methods for the determination of vigabatrin in tablets.

Two sensitive and selective spectrofluorimetric and spectrophotometric methods have been developed for the determination of vigabatrin in tablets. The methods are based on derivatization with 7-chloro-4-nitrobenzofurazan (NBD-Cl). The product showed an absorption maximum at 460 nm and a fluorescence emission peak at 520 nm in ethyl acetate. The color was found to be stable for at least 48 h in this solvent. The optimum conditions of the reaction were investigated and it was found that the reaction proceeds quantitatively at pH 10.0, 70 degrees C in 50 min when the mole ratio of the reagent to drug was 30. The reaction obeys Beer's law over the ranges of 2-10 and 0.05-1.00 microg ml(-1) for the spectrophotometric and spectrofluorimetric measurements, respectively. The detection limits were found to be 0.50 and 0.01 microg ml(-1) for the spectrophotometric and spectrofluorimetric methods, respectively. The proposed methods were applied to the assay of vigabatrin in tablets. The results were compared statistically with those obtained by the modified spectrofluorimetric method reported in the literature.

7,7,8,8-Tetracyanoquinodimethane as a new derivatization reagent for high-performance liquid chromatography and thin-layer chromatography: rapid screening of plasma for some antidepressants.

Using 7,7,8,8-tetracyanoquinodimethane (TCNQ) as a new derivatization reagent for HPLC and TLC, novel methods are described to detect secondary amine-bearing antidepressants (paroxetine, desipramine, fluoxetine, nortriptyline, maprotiline). The HPLC method is sensitive enough to detect these drugs in plasma at therapeutic levels whereas the latter has potential to detect them in overdose or forensic cases. The methods are based on purple chromogens formed by the displacement reaction of the drugs with TCNQ. The resulting chromogens are directly separated by either reversed-phase HPLC on a C(18) column or TLC on silicagel plates. For HPLC, acetonitrile-water (60:40) was used as mobile phase, with detection at 567 nm and separation in 40 min. For TLC, three developing solvent systems were used. By HPLC, 36 ng ml(-1) spiked plasma concentration of the drugs gave easily detectable signals whereas by TLC, detection limits varied mostly between 240 and 480 ng ml(-1). The HPLC method was applied to real plasma samples. The methods described are simple and very selective; some metabolites of these antidepressants and a vast number of drugs do not interfere with detection.