Differentiation between naproxen, naproxen–protein conjugates, and naproxen–lysine in plasma via micellar electrokinetic capillary chromatography—a new approach in the bioanalysis of drug targeting preparations

Author:

Albrecht Christiane1,Reichen Jürg1,Visser Jan2,Meijer Dirk K F2,Thormann Wolfgang1

Affiliation:

1. Department of Clinical Pharmacology, University of Bern, Murtenstr. 35, 3010 Bern, Switzerland

2. Department of Pharmacokinetics and Drug Delivery, University of Groningen, Antonius Deusinglaan 2, 9713 AV Groningen, The Netherlands

Abstract

Abstract Pharmacotherapy through the targeting of drugs is a promising new approach that requires adequate analytical methods capable of differentiating between the free drug, the drug carrier, and metabolites. Using micellar electrokinetic capillary chromatography (MECC), we report the separation of naproxen (NAP) from NAP covalently coupled to human serum albumin or to mannosylated serum albumin and the metabolite naproxen–lysine. An assay for selective analysis of the different forms of NAP by direct plasma injection was developed with salicylate as internal standard and solute detection by laser-induced fluorescence. Compared with previously applied techniques, including HPLC and total plasma fluorescence, MECC offers the advantage that free and covalently bound NAP can be differentiated in one run and can be accurately monitored in microliter quantities of plasma. Summation of all NAP equivalents determined by MECC revealed data that compare well with those produced by total plasma fluorescence and HPLC.

Publisher

Oxford University Press (OUP)

Subject

Biochemistry (medical),Clinical Biochemistry

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