Quantitative determination of dextran-naproxen ester pro-drugs with varying molecular weights and degrees of substitution in biological media by means of high-performance size exclusion chromatography with fluorescence detection.
A high-performance size exclusion chromatographic procedure using a Nucleosil Diol column and fluorescence detection has been developed for the determination of dextran-naproxen ester pro-drugs with varying molecular weights and degrees of substitution in aqueous buffer solutions and biological media in the presence of the parent drug. The effect of several variables on the chromatographic behaviour of the compounds is discussed. Linear standard calibration curves were constructed for all the dextran derivatives incubated in whole blood and urine (human and rabbit), rabbit liver homogenate and human synovial fluid. In whole blood, the detection limit (lambda ex = 330 nm, lambda em = 360 nm) for a dextran T-70 pro-drug with a degree of substitution (DS) of 10.6 was found to be 2 micrograms ml-1 after applying a 20-micrograms sample to the column. The assay has been used in stability studies and determination of plasma concentration-time profiles after intravenous administration to rabbits of dextran-naproxen ester pro-drugs.
Larsen
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Department of Pharmaceutics, Royal Danish School of Pharmacy, Copenhagen, Denmark.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003911:Dextrans / Q000032:analysis / Q000097:blood* / Q000652:urine; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D009288:Naproxen / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000652:urine; D011355:Prodrugs / Q000032:analysis / Q000493:pharmacokinetics*; D011817:Rabbits
D003911:Dextrans; D011355:Prodrugs; C069669:dextran naproxen ester; D009288:Naproxen