Separation of metronidazole, its major metabolites and their conjugates using dynamically modified silica

U. G. Thomsen; Claus Cornett; J. Tjornelund; S. H. Hansen

Separation of metronidazole, its major metabolites and their conjugates using dynamically modified silica

U. G. Thomsen, Claus Cornett, J. Tjornelund, S. H. Hansen

8 Citationer (Scopus)

Abstract

Metronidazole has previously been used as a probe when investigating cytochrome P450 isoenzymes and thus the pattern of metabolism of this drug has been extensively studied. However, in previous investigations the conjugates were determined by indirect methods. In this paper we present a high-performance liquid chromatographic (HPLC) system for the simultaneous determination of metronidazole, its major metabolites and their glucuronic acid conjugates in biological fluids. The separation is performed using bare silica dynamically modified with N-cetyl-N,N,N-trimethylammonium bromide contained in the mobile phase. The separation of the acidic metabolites of metronidazole is greatly improved with this system compared to other published reversed-phase HPLC systems intended for the same purpose. Glucuronides of metronidazole and its hydroxy metabolites have been synthesized in vitro using rat liver microsomes and preparative HPLC. The method developed makes it possible to determine the intact glucuronic acid conjugates of metronidazole and the hydroxy metabolite in human urine.

Originalsprog	Engelsk
Tidsskrift	Journal of Chromatography A
Vol/bind	697
Udgave nummer	1-2
Sider (fra-til)	175-184
Antal sider	10
ISSN	0021-9673
Status	Udgivet - 1995

Emneord

performance liquid-chromatography human-plasma tinidazole assay urine liver feces

Citationsformater

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title = "Separation of metronidazole, its major metabolites and their conjugates using dynamically modified silica",

abstract = "Metronidazole has previously been used as a probe when investigating cytochrome P450 isoenzymes and thus the pattern of metabolism of this drug has been extensively studied. However, in previous investigations the conjugates were determined by indirect methods. In this paper we present a high-performance liquid chromatographic (HPLC) system for the simultaneous determination of metronidazole, its major metabolites and their glucuronic acid conjugates in biological fluids. The separation is performed using bare silica dynamically modified with N-cetyl-N,N,N-trimethylammonium bromide contained in the mobile phase. The separation of the acidic metabolites of metronidazole is greatly improved with this system compared to other published reversed-phase HPLC systems intended for the same purpose. Glucuronides of metronidazole and its hydroxy metabolites have been synthesized in vitro using rat liver microsomes and preparative HPLC. The method developed makes it possible to determine the intact glucuronic acid conjugates of metronidazole and the hydroxy metabolite in human urine.",

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author = "Thomsen, {U. G.} and Claus Cornett and J. Tjornelund and Hansen, {S. H.}",

year = "1995",

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journal = "Journal of Chromatography A",

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TY - JOUR

T1 - Separation of metronidazole, its major metabolites and their conjugates using dynamically modified silica

AU - Thomsen, U. G.

AU - Cornett, Claus

AU - Tjornelund, J.

AU - Hansen, S. H.

PY - 1995

Y1 - 1995

N2 - Metronidazole has previously been used as a probe when investigating cytochrome P450 isoenzymes and thus the pattern of metabolism of this drug has been extensively studied. However, in previous investigations the conjugates were determined by indirect methods. In this paper we present a high-performance liquid chromatographic (HPLC) system for the simultaneous determination of metronidazole, its major metabolites and their glucuronic acid conjugates in biological fluids. The separation is performed using bare silica dynamically modified with N-cetyl-N,N,N-trimethylammonium bromide contained in the mobile phase. The separation of the acidic metabolites of metronidazole is greatly improved with this system compared to other published reversed-phase HPLC systems intended for the same purpose. Glucuronides of metronidazole and its hydroxy metabolites have been synthesized in vitro using rat liver microsomes and preparative HPLC. The method developed makes it possible to determine the intact glucuronic acid conjugates of metronidazole and the hydroxy metabolite in human urine.

AB - Metronidazole has previously been used as a probe when investigating cytochrome P450 isoenzymes and thus the pattern of metabolism of this drug has been extensively studied. However, in previous investigations the conjugates were determined by indirect methods. In this paper we present a high-performance liquid chromatographic (HPLC) system for the simultaneous determination of metronidazole, its major metabolites and their glucuronic acid conjugates in biological fluids. The separation is performed using bare silica dynamically modified with N-cetyl-N,N,N-trimethylammonium bromide contained in the mobile phase. The separation of the acidic metabolites of metronidazole is greatly improved with this system compared to other published reversed-phase HPLC systems intended for the same purpose. Glucuronides of metronidazole and its hydroxy metabolites have been synthesized in vitro using rat liver microsomes and preparative HPLC. The method developed makes it possible to determine the intact glucuronic acid conjugates of metronidazole and the hydroxy metabolite in human urine.

KW - performance liquid-chromatography human-plasma tinidazole assay urine liver feces

M3 - Journal article

SN - 0021-9673

VL - 697

SP - 175

EP - 184

JO - Journal of Chromatography A

JF - Journal of Chromatography A

IS - 1-2

ER -