Absorptiometric, Polarographic, and Gas Chromatographic Assays for the Determination of N-1-substituted Nitroimidazoles in Blood and Urine

Silva, J.A.F. De; Munno, Nancy; Strojny, Norman

doi:10.1002/jps.2600590213

Cited by 44 publications

(7 citation statements)

References 7 publications

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“…Biological assays (10, 13, 18) and gas chromatographic procedures (15, 27) do not possess the potential for measuring metabolic products. Polarographic methods (3,11,24) detect all compounds containing the unchanged nitro group but do not measure the individual substances. Using thin-layer chromatography and subsequent polarography, Stambaugh et al (20) identified the metabolites in urine after metronidazole administration to humans.…”

Section: Resultsmentioning

confidence: 99%

Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects

Nilsson-Ehle¹,

Ursing²,

Nilsson‐Ehle³

1981

Antimicrob Agents Chemother

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We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase highpressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected.The two nitroimidazoles metronidazole and tinidazole have been used as antiprotozoal agents for many years. These compounds also possess excellent inhibitory activity against anaerobic bacteria (4, 5, 9, 21, 24) and are used increasingly for treatment of infections caused by these microorganisms.Metronidazole is metabolized in the liver mainly by oxidative processes; the two major metabolites excreted in urine are 1-(2-hydroxyethyl) -2 -hydroxy -methyl -5-nitroimidazole(hydroxy metabolite) and 2-methyl-5-nitroimidazole-1-acetic acid (acetic acid metabolite) (20). High-pressure liquid chromatography methods have been developed to measure the parent compound metronidazole and its two major metabolites (6, 12, 25). Measurements of tinidazole by using high-pressure liquid chromatography have also been reported (12,16).We report here a rapid and simple assay involving high-pressure liquid chromatography for quantitation of metronidazole and its two main metabolites in serum and urine; with a slight alteration in the composition of the mobile phase, this assay was also used for quantitation of tinidazole. The

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Section: Resultsmentioning

confidence: 99%

Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects

Nilsson-Ehle¹,

Ursing²,

Nilsson‐Ehle³

1981

Antimicrob Agents Chemother

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“…were reported for the determination of metronidazole using Polarographic and Colorimetric techniques [5][6][7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Reduction of Metronidazole and Its Determination in Pharmaceutical Dosage Forms by D.C. Polarography

Zuhri¹,

Al-Khalil²,

Suleiman³

1986

Analytical Letters

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A simple d.c. polarographic method has been developed for the determination of metronidazole in dosages forms. In Robinson -Britton buffer (pH 4.38) and in presence of 1.60X10-3% Triton X-100, the drug produced a well defined 4-electron polarographic wave followed by another wave of about half the height of the first wave. The current is proportional to the concentration and permits the drug to be determined by d.c. polarography in the concentration range 5.0X10-5-7.0X10-4M.Results obtained by the proposed method are in excellent agreement with that provided by the USP-XX method. A rapid, sensitive and accurate polarographic method for the determination of metronidazole in the tablets which are produced locally is proposed.

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“…To determine its serum concentration, a number of analytical methods have been described, including polarography (Crooper and Hodless 1967;De Silva et al, 1970), spectrophotometry (Petrik et al, 1994;Parimos and Umapath, 1994), spectrofluorimetry (Laue et al, 1969;Laufen et al, 1979), gas chromatography (Laufen et al, 1979;Midha et al, 1981;Wood, 1975;Bhatia and Shanbhag, 1984) and thin-layer chromatography with densitometry (Welling and Munro, 1972). A wide variety of revered-phase high-performance liquid chromatographic (RP-HPLC) procedures have been described using sample pre-treatments such as solvent extraction, protein precipitation or solid-phase extraction (Menouer et al, 1987;Pyorala et al, 1994;Tendolkar et al, 1994).…”

Section: Tinidazole (1 -[2-ethylsulphony1)-ethyl]-2-methyl-5-nitroimimentioning

confidence: 99%

Direct Assay of Tinidazole in Human Serum by Micellar Liquid Chromatography

Habel

Guermouche

1997

Biomed. Chromatogr.

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A liquid chromatographic procedure for the direct determination of tinidazole in human serum is presented. It includes the use of a micellar mobile phase consisting of SDS (5.10−2 M): propan‐1‐ol; (94:6; v/v) and a μBondapak CN column with UV detection at 320 nm. No solvent extraction or deproteinization are necessary. The linearity (0.1–10 mg L), the precision (3%), the reproducibility (1.3%), the recovery (99%), and the detection limit (0.1 mg L) in the tinidazole determination are comparable and sometimes greater than the corresponding tinidazole parameters when deproteinization and conventional reversed‐phase HPLC are used. One hundred injections of serum samples do not affect the column life. The procedure is applied to ascertain the pharmacokinetics of 10 mg/kg of tinidazole. © 1997 by John Wiley & Sons, Ltd.

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Absorptiometric, Polarographic, and Gas Chromatographic Assays for the Determination of N-1-substituted Nitroimidazoles in Blood and Urine

Cited by 44 publications

References 7 publications

Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects

Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects

Electrochemical Reduction of Metronidazole and Its Determination in Pharmaceutical Dosage Forms by D.C. Polarography

Direct Assay of Tinidazole in Human Serum by Micellar Liquid Chromatography

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