Determination of Fluconazole in Biological Fluids by Capillary Column Gas Chromatography with a Nitrogen Detector

Debruyne, Danièle; Ryckelynck, J. P.; Bigot, M.-C.; Moulin, Maryline

doi:10.1002/jps.2600770615

Cited by 33 publications

(13 citation statements)

References 6 publications

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“…This can be summarized as the following: The literature survey reveals several analytical methods used for quantitative determination of FLZ in body fluids and pharmaceutical preparations. These methods include high-performance liquid chromatography [2][3][4][5][6][7][8] , liquid chromatography-tandem mass spectrometry [9][10][11] , gas chromatography [12][13][14][15] ,micellar electrokinetic capillary chromatography 16 and bioassay 17 .…”

Section: Theory Of Ratio Difference Spectrophotometric Methods (Rdsm)mentioning

confidence: 99%

Novel Spectrophotometric Methods for the Determination of Fluconazole in the Presence of Its Oxidative Degradation Product

Lotfy

Monir

El-Aleem

2012

J. Chil. Chem. Soc.

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Five sensitive, selective and precise spectrophotometric stability-indicating methods for the determination of fluconazole in the presence of its oxidative degradation product and in pharmaceutical formulations are developed and validated. Method A is a newly developed spectrophotometric one that is called ratio difference method by measuring the difference in amplitudes between 261.5 and 266.5 nm of ratio spectrum. Method B is a third derivative spectrophotometric one, which determines peak amplitudes from 265.5-268nm (peak-peak). Method C is ratio subtraction method. Method D is the first derivative of the ratio spectra by measuring the peak amplitude at 269 nm. Finally, method E is the mean centering of ratio spectra method by measuring the peak amplitude at 266.5 nm. The proposed methods allow the determination of fluconazole in the presence of its oxidative degradation product over a concentration range of 50-400 µg.mL -1 with mean percentage recoveries of 100.24±0.91, 99.91±0.52, 100.20±1.26, 99.79±0.69, and 100.77±0.72 respectively.The selectivity of the proposed methods is checked using laboratory prepared mixtures. The proposed methods have been successfully applied to the analysis of fluconazole in pharmaceutical dosage forms without interference from other dosage form additives and the results have been statistically compared with a reported method.

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Section: Theory Of Ratio Difference Spectrophotometric Methods (Rdsm)mentioning

confidence: 99%

Novel Spectrophotometric Methods for the Determination of Fluconazole in the Presence of Its Oxidative Degradation Product

Lotfy

Monir

El-Aleem

2012

J. Chil. Chem. Soc.

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“…To determine the accuracy of the bioassay, spiked unknowns containing 4.97, 9.9, 14.78, 19.6, 24.4, 29.1, 33.8, and 38.5 ,g of fluconazole per ml were assayed three to six times on separate occasions. The values obtained were averaged and correlated with the expected values.…”

Section: Resultsmentioning

confidence: 99%

“…While it is generally not necessary to measure fluconazole levels, the dose of fluconazole must be adjusted in patients with renal insufficiency (3) and may require adjustment in patients taking drugs which interact with fluconazole (10). The most commonly described assays for fluconazole levels are high-pressure liquid chromatography (HPLC) (5) and gas-liquid chromatography (4,8,14), but these methods require expensive equipment and considerable technician time. As an alternative, we considered several bioassay methods.…”

mentioning

confidence: 99%

Standardization of a fluconazole bioassay and correlation of results with those obtained by high-pressure liquid chromatography

Rex

Hanson

Amantea

et al. 1991

Antimicrob Agents Chemother

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Fluconazole is a recently marketed triazole antifungal agent that has been found useful in the treatment of mucocutaneous candidiasis and cryptococcal meningitis (1). While it is generally not necessary to measure fluconazole levels, the dose of fluconazole must be adjusted in patients with renal insufficiency (3) and may require adjustment in patients taking drugs which interact with fluconazole (10). The most commonly described assays for fluconazole levels are high-pressure liquid chromatography (HPLC) (5) and gas-liquid chromatography (4,8,14), but these methods require expensive equipment and considerable technician time. As an alternative, we considered several bioassay methods. When an itraconazole bioassay using Difco nutrient agar, pH 6.0, was tested for fluconazole (6), small zones of diffusion, a lower limit of sensitivity of about 4 ,ug/ml, and fuzzy zone edges were observed. The system using Pfizer High Resolution agar (used according to the manufacturer's instructions) produced sharp zones and good sensitivity, but its requirement for special agar (obtainable only from Pfizer Pharmaceuticals), and a dedicated 28°C incubator made it otherwise unattractive. A thin-layer yeast nitrogen brothpeptone agar system (2, 7) was designed for use with round petri dishes (150 by 15 mm), allowing only 10 samples per plate. When larger plates (245 by 245 mm) were used, the zone diameters of duplicate wells had excessive variability. Finally, a SAAMF (synthetic amino acid medium for fungi) agar-based assay that we developed to detect very low concentrations of fluconazole (12) required a difficult, tedious technique that was not suitable for large-scale work. In response to these difficulties, we developed a modified bioassay that was suitable for measuring fluconazole con-* Corresponding author. centrations in the clinically relevant range of 2 to 40 jig/ml.Further, as we were unable to find any information correlating bioassay and HPLC results for fluconazole and as a further validation of the new bioassay technique, we performed a blind comparison of these two methods for measuring fluconazole concentrations. MATERIALS AND METHODSReagents. Fluconazole powder (lot R29) was a gift from Pfizer Pharmaceuticals. All standards and spiked unknowns were prepared from this one lot. Pooled lots of human serum and plasma were prepared from groups of four to five healthy donors, while a pooled lot of human cerebrospinal fluid (CSF) was collected from patients undergoing lumbar puncture. Patient CSF was added to the pooled lot only when it was known that the routine analysis of the CSF was unremarkable and that the patient was not taking any antifungal drugs. Sufficiently large lots of each of the three fluids were collected to allow all standards and unknowns used throughout this study to be prepared from these pooled lots.The HPLC method used spectral grade ethyl acetate and methanol (American Scientific Products, American Hospital Supply Corporation, Muskegan, Mich.), analytical grade sodium phosphate (Fisher Scientific,...

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“…Peak serum levels with chronically administered dosages of 50 and 400 mg/day typically result in fluconazole concentrations of 2 and 14 ,ug/ml, respectively (4). Maintenance therapy with an oral fluconazole dose of 100 mg (2) or 200 mg (2, 4) once daily has been shown to be highly effective in preventing recurrent cryptococcal infections.Previously published assays for fluconazole include bioassay (11), high-pressure liquid chromatography (3, 6), gas chromatography with electron capture (GC-EC) detection (12), and GC with nitrogen selective detector (5,8). GC-EC detection is a sensitive method; however, the published method requires three extraction steps and inactivation of the GC column to obtain good chromatographic resolution and better peak shapes.…”

mentioning

confidence: 99%

“…Previously published assays for fluconazole include bioassay (11), high-pressure liquid chromatography (3,6), gas chromatography with electron capture (GC-EC) detection (12), and GC with nitrogen selective detector (5,8). GC-EC detection is a sensitive method; however, the published method requires three extraction steps and inactivation of the GC column to obtain good chromatographic resolution and better peak shapes.…”

mentioning

confidence: 99%

Rapid and sensitive assay for fluconazole which uses gas chromatography with electron capture detection

Rege

Walker-Cador

Clark

et al. 1992

Antimicrob Agents Chemother

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Fluconazole, an orally active antifungal agent, has been shown to be clinically beneficial for maintenance therapy of cryptococcal meningitis. A sensitive gas-liquid chromatographic assay with electron capture detection, which required only a single extraction step and precluded any pretreatment of the chromatographic column, was developed for fluconazole. The assay was linear from 0.1 to 20 p,g/ml, with a correlation coefficient of 0.999. The intraassay and interassay coefficients of variation were less than 9%o. The measured values on average were within 8% of the target values. The extraction recoveries ranged from 87 to 106%. Steady-state plasma fluconazole levels (mean + standard deviation) in three AIDS patients with cryptococcal meningitis receiving 200 mg of fluconazole per day ranged from 8.95 1.32 to 11.41 + 0.63 ,ug/ml and were within the expected range for this dosing rate, on the basis of previous studies. The ratio of fluconazole concentration in cerebrospinal fluid to fluconazole concentration in plasma in one patient receiving 400 mg/day was 0.73 at steady state and was consistent with published reports.Fluconazole is an orally active, triazole antifungal agent recently approved by the Food and Drug Administration for treatment of candidiasis and cryptococcal meningitis in patients with AIDS. Advantages of fluconazole are its water solubility, low level of protein binding, high bioavailability, long half-life, metabolic stability (7), and high cerebrospinal fluid (CSF) penetration (1, 3, 11). It can be given orally or intravenously and is usually well tolerated, with no major adverse reactions (2, 9, 10). Peak serum levels with chronically administered dosages of 50 and 400 mg/day typically result in fluconazole concentrations of 2 and 14 ,ug/ml, respectively (4). Maintenance therapy with an oral fluconazole dose of 100 mg (2) or 200 mg (2, 4) once daily has been shown to be highly effective in preventing recurrent cryptococcal infections.Previously published assays for fluconazole include bioassay (11), high-pressure liquid chromatography (3, 6), gas chromatography with electron capture (GC-EC) detection (12), and GC with nitrogen selective detector (5,8). GC-EC detection is a sensitive method; however, the published method requires three extraction steps and inactivation of the GC column to obtain good chromatographic resolution and better peak shapes. We report here a GC-EC detection method that requires only a single extraction step and no preinactivation treatment of the column and that results in excellent chromatographic resolution with sharp and symmetrical peaks.MATERUILS AND METHODS Materials and reagents. Fluconazole was obtained from Pfizer Central Research, Groton, Conn. The internal standard for this assay (4,4'-dibromobiphenyl) was purchased from Aldrich Chemical Co., Milwaukee, Wis. The structures of these compounds are shown in Fig. 1. Analytical-grade methanol, ethyl acetate, sodium hydroxide, and sodium chloride were purchased from Fisher Scientific, Pittsburgh, * Corresponding...

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Determination of Fluconazole in Biological Fluids by Capillary Column Gas Chromatography with a Nitrogen Detector

Cited by 33 publications

References 6 publications

Novel Spectrophotometric Methods for the Determination of Fluconazole in the Presence of Its Oxidative Degradation Product

Novel Spectrophotometric Methods for the Determination of Fluconazole in the Presence of Its Oxidative Degradation Product

Standardization of a fluconazole bioassay and correlation of results with those obtained by high-pressure liquid chromatography

Rapid and sensitive assay for fluconazole which uses gas chromatography with electron capture detection

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