Simultaneous quantitative determination of naproxen, its metabolite 6-O-desmethylnaproxen and their five conjugates in plasma and urine samples by high-performance liquid chromatography on dynamically modified silica.
The glucuronides of the anti-inflammatory drug naproxen and its metabolite 6-O-desmethylnaproxen have been produced on a preparative scale by enzymatic synthesis. 6-O-Desmethylnaproxen, the glycine conjugate of naproxen and the O-sulphate of 6-O-desmethylnaproxen were prepared by chemical synthesis. Naproxen and the purified metabolite and conjugates were used as standards for the analytical investigation of the metabolic pattern of naproxen in humans. A reversed-phase high-performance liquid chromatographic method based on bare silica dynamically modified with cetyltrimethylammonium ions has been developed. The system was optimized to give a separation of naproxen, 6-O-desmethylnaproxen and five conjugates. Using this method it is also possible to deduce the relationship between the amount of the intact ether-glucuronide and acyl-glucuronide of 6-O-desmethylnaproxen.
Andersen
J V
JV
PharmaBiotec Research Centre, Royal Danish School of Pharmacy, Department of Organic Chemistry, Copenhagen.
Hansen
S H
SH
D000328:Adult; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009288:Naproxen / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011817:Rabbits; D012016:Reference Values; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
D005965:Glucuronates; D009288:Naproxen; C034451:desmethylnaproxen