Rapid determination of serum levels of a new antifungal agent, fluconazole, by high-performance liquid chromatography

Hosotsubo, Kikumi; Hosotsubo, Hideo; Nishijima, Masako K.; Okada, Toshiki; Taenaka, Nobuyuki; Yoshiya, Ikuto

doi:10.1016/s0378-4347(00)83826-8

Cited by 28 publications

(9 citation statements)

References 5 publications

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“…Serum and hemofiltrate samples were stored at -80 ~ C until analyzed for fluconazole concentration by high-performance liquid chromatography (HPLC), as described previously [7]. In brief, proteins were precipitated by adding acetonitrile.…”

Section: Methodsmentioning

confidence: 99%

Fluconazole is removed by continuous venovenous hemofiltration in a liver transplant patient

et al. 1995

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Fluconazole is effective for the treatment of fungal infections. A continuous venovenous hemofiltration (CVVH) was necessary in a liver transplant patient with anuria. Fluconazole treatment was started after the diagnosis of systemic candidiasis. There was no adverse effect on liver function, and the immunosuppression with cyclosporine was not affected. It is shown for the first time that CVVH effectively removes fluconazole from the blood circulation by a clearance into the hemofiltrate of approximately 21 ml/min. These data suggest that the treatment of fungal infections with fluconazole does not necessitate a reduction of the dosage during CVVH.

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Section: Methodsmentioning

confidence: 99%

Fluconazole is removed by continuous venovenous hemofiltration in a liver transplant patient

et al. 1995

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“…This method reduced the analysis time compared to the existing FLA method using I.S. (>11.8 min) [7,9,11,[13][14][15].…”

Section: Hplc Chromatogrammentioning

confidence: 99%

“…Several HPLC methods for determining FLA levels in human plasma have been described [7][8][9][10][11][12][13][14][15][16]. The majority utilize ultraviolet detection (UV) and a reversed-phase octadecylsilyl (C 18 ) column.…”

Section: Introductionmentioning

confidence: 99%

“…The majority utilize ultraviolet detection (UV) and a reversed-phase octadecylsilyl (C 18 ) column. However, existing methods have shortcomings in terms of pharmacokinetic studies, i.e., a narrow concentration range (LLOQ ≥ 0.2 g/mL) [7][8][9][10][11][12][13], lengthy running times (>10.0 min) [7,[9][10][11][13][14][15][16] and the lack of an internal standard (I.S.) [8][9][10]12,16].…”

Section: Introductionmentioning

confidence: 99%

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An optimized analytical method of fluconazole in human plasma by high-performance liquid chromatography with ultraviolet detection and its application to a bioequivalence study

Kim¹,

Im²,

Kang³

et al. 2007

Journal of Chromatography B

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“…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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Rapid determination of serum levels of a new antifungal agent, fluconazole, by high-performance liquid chromatography

Cited by 28 publications

References 5 publications

Fluconazole is removed by continuous venovenous hemofiltration in a liver transplant patient

Fluconazole is removed by continuous venovenous hemofiltration in a liver transplant patient

An optimized analytical method of fluconazole in human plasma by high-performance liquid chromatography with ultraviolet detection and its application to a bioequivalence study

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

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