Abstract
A rapid and sensitive high-pressure liquid chromatography assay for metronidazole and its two principle metabolites, 1-(2-hydroxyethyl-2-hydroxymethyl)-5-nitro-imidazole [hydroxy metabolite] and 1-acetic acid-2-methyl-5-metronidazole [acid metabolite], was developed. The retention times observed were 5.7, 3.3, and 4.5 min, respectively. A reverse-phase μC18 Bondapak column using a solvent system of methanol, acetonitrile, and 0.005 M pH 4 potassium dihydrogen phosphate (4:3:93, vol/vol) was used to achieve separation of the three compounds. Patients receiving metronidazole therapy were given a loading dose of 13.6 mg of drug per kg intravenously over 1 h, followed by a maintenance dose of 1.43 mg/kg per h. The range of metronidazole concentrations observed was 6.8 to 47.5 μg/ml. These levels are well above the minimal inhibitory concentrations of most clinically significant anaerobic bacteria including Bacteroides fragilis. Little of the acid metabolite was observed in the plasma. The concentration of hydroxy metabolite ranged from 1.6 to 16 μg/ml. The latter may represent an additional source of antimicrobial activity since the hydroxy metabolite has approximately 30% the biological activity of metronidazole.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Grunberg E., Titsworth E. H. Chemotherapeutic properties of heterocyclic compounds: monocyclic compounds with five-membered rings. Annu Rev Microbiol. 1973;27:317–346. doi: 10.1146/annurev.mi.27.100173.001533. [DOI] [PubMed] [Google Scholar]
- Midha K. K., McGilveray I. J., Cooper J. K. Determination of therapeutic levels of metronidazole in plasma by gas-liquid chromatography. J Chromatogr. 1973 Dec 19;87(2):491–497. doi: 10.1016/s0021-9673(01)91751-0. [DOI] [PubMed] [Google Scholar]
- Nastro L. J., Finegold S. M. Bactericidal activity of five antimicrobial agents against Bacteroides fragilis. J Infect Dis. 1972 Jul;126(1):104–107. doi: 10.1093/infdis/126.1.104. [DOI] [PubMed] [Google Scholar]
- Ralph E. D., Kirby W. M. Bioassay of metronidazole with either anaerobic or aerobic incubation. J Infect Dis. 1975 Nov;132(5):587–591. doi: 10.1093/infdis/132.5.587. [DOI] [PubMed] [Google Scholar]
- Speck W. T., Stein A. B., Rosenkranz H. S. Metronidazole bioassay. Antimicrob Agents Chemother. 1976 Feb;9(2):260–261. doi: 10.1128/aac.9.2.260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wood N. F. GLC analysis of metronidazole in human plasma. J Pharm Sci. 1975 Jun;64(6):1048–1049. doi: 10.1002/jps.2600640642. [DOI] [PubMed] [Google Scholar]