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. 1992 Mar;36(3):647–650. doi: 10.1128/aac.36.3.647

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

A B Rege 1, J Y Walker-Cador 1, R A Clark 1, J J Lertora 1, N E Hyslop Jr 1, W J George 1
PMCID: PMC190572  PMID: 1622178

Abstract

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 micrograms/ml, with a correlation coefficient of 0.999. The intraassay and interassay coefficients of variation were less than 9%. 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 micrograms/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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arndt C. A., Walsh T. J., McCully C. L., Balis F. M., Pizzo P. A., Poplack D. G. Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system. J Infect Dis. 1988 Jan;157(1):178–180. doi: 10.1093/infdis/157.1.178. [DOI] [PubMed] [Google Scholar]
  2. Bozzette S. A., Larsen R. A., Chiu J., Leal M. A., Jacobsen J., Rothman P., Robinson P., Gilbert G., McCutchan J. A., Tilles J. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med. 1991 Feb 28;324(9):580–584. doi: 10.1056/NEJM199102283240902. [DOI] [PubMed] [Google Scholar]
  3. Foulds G., Brennan D. R., Wajszczuk C., Catanzaro A., Garg D. C., Knopf W., Rinaldi M., Weidler D. J. Fluconazole penetration into cerebrospinal fluid in humans. J Clin Pharmacol. 1988 Apr;28(4):363–366. doi: 10.1002/j.1552-4604.1988.tb03159.x. [DOI] [PubMed] [Google Scholar]
  4. Galgiani J. N. Fluconazole, a new antifungal agent. Ann Intern Med. 1990 Aug 1;113(3):177–179. doi: 10.7326/0003-4819-113-3-177. [DOI] [PubMed] [Google Scholar]
  5. Harris S. C., Wallace J. E., Foulds G., Rinaldi M. G. Assay of fluconazole by megabore capillary gas-liquid chromatography with nitrogen-selective detection. Antimicrob Agents Chemother. 1989 May;33(5):714–716. doi: 10.1128/aac.33.5.714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hosotsubo K. K., Hosotsubo H., Nishijima M. K., Okada T., Taenaka N., Yoshiya I. Rapid determination of serum levels of a new antifungal agent, fluconazole, by high-performance liquid chromatography. J Chromatogr. 1990 Jul 13;529(1):223–228. doi: 10.1016/s0378-4347(00)83826-8. [DOI] [PubMed] [Google Scholar]
  7. Humphrey M. J., Jevons S., Tarbit M. H. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother. 1985 Nov;28(5):648–653. doi: 10.1128/aac.28.5.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Robinson P. A., Knirsch A. K., Joseph J. A. Fluconazole for life-threatening fungal infections in patients who cannot be treated with conventional antifungal agents. Rev Infect Dis. 1990 Mar-Apr;12 (Suppl 3):S349–S363. doi: 10.1093/clinids/12.supplement_3.s349. [DOI] [PubMed] [Google Scholar]
  9. Sugar A. M., Saunders C. Oral fluconazole as suppressive therapy of disseminated cryptococcosis in patients with acquired immunodeficiency syndrome. Am J Med. 1988 Oct;85(4):481–489. doi: 10.1016/s0002-9343(88)80082-2. [DOI] [PubMed] [Google Scholar]
  10. Tucker R. M., Williams P. L., Arathoon E. G., Levine B. E., Hartstein A. I., Hanson L. H., Stevens D. A. Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis. Antimicrob Agents Chemother. 1988 Mar;32(3):369–373. doi: 10.1128/aac.32.3.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Wood P. R., Tarbit M. H. Gas chromatographic method for the determination of fluconazole, a novel antifungal agent, in human plasma and urine. J Chromatogr. 1986 Nov 28;383(1):179–186. doi: 10.1016/s0378-4347(00)83458-1. [DOI] [PubMed] [Google Scholar]

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