Simultaneous determination of the phase II metabolites of the non steroidal anti-inflammatory drug etodolac in human urine.
Etodolac, an antirheumatic and analgetic drug, is metabolized in humans by hydroxylation and acyl glucuronidation to yield the corresponding 1-O-glucuronides. The acylglucuronides of etodolac and one of its hydroxylated metabolites were determined by HPLC using a RP18 column. In order to increase the lipophilicity of these metabolites the hydroxy groups were acetylated and the carboxylic functions were methylated. In a study with five human volunteers a stereoselective excretion of the acylglucuronides could be observed. The S-etodolac-glucuronide is mainly excreted during the first 6 hours after administration of 400 mg of etodolac whereas the elimination of the R-glucuronide predominates at longer periods of time. The S-glucuronide of 7-hydroxy-etodolac was preferenetively excreted during the period of time observed. An unknown metabolite of etodolac could be characterized by chemical and enzymatically hydrolysis and by MS and NMR.
Institute of Pharmaceutical Chemistry, University of Münster, Germany.
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Berendes
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Blaschke
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D017308:Etodolac / Q000378:metabolism* / Q000652:urine; D005965:Glucuronates / Q000737:chemistry* / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005965:Glucuronates; D017308:Etodolac