AN ALTERNATIVE LIQUID CHROMATOGRAPHY-MASS SPECTROMETRIC METHOD FOR THE DETERMINATION OF AZITHROMYCIN IN HUMAN PLASMA AND ITS APPLICATION TO PHARMACOKINETIC STUDY

摘要

A simple, sensitive, selective, and reproducible method based on high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (LC/MS) was developed for the determination of a macrolide antibiotic azithromycin in human plasma. The internal standard (roxithromycin) was separated from azithromycin on a Hypersil Gold C₁₈ column, with retention times of 10.71 and 13.67 min, respectively. The mobile phase consisted of a mixture of 20 mM ammonium acetate buffer (pH 5.2), acetonitrile and methanol (50:40:10, v/v/v), running through the column at a flow rate of 0.3 mL/min. The chromatographic analysis was operated at 25°C. Sample preparation was prepared by liquid-liquid extraction with a mixture of 7:3 (v/v) diethylether:dichloromethane. The precision of the method based on within-day repeatability and reproducibility (day-to-day variation) was below 5% (% coefficient of variations: % CV). Good accuracy was observed for both the intra-day or inter-day assays. Limit of quantification was accepted as 1 ng using 200 μL plasma samples. The mean recoveries for azithromycin and the internal standard were greater than 85%. The method was applied successfully to the investigation of the pharmacokinetics of azithromycin when given in combination with fosmidomycin as oral doses of 750 mg twelve hourly for 3 days in a total of 5 Thai male patients with acute uncomplicated falciparum malaria.View full textDownload full textKeywordsazithromycin, human plasma, liquid chromatography, mass-spectrometry, pharmacokineticsRelated var addthis_config = { ui_cobrand: "Taylor & Francis Online", services_compact: "citeulike,netvibes,twitter,technorati,delicious,linkedin,facebook,stumbleupon,digg,google,more", pubid: "ra-4dff56cd6bb1830b" }; Add to shortlist Link Permalink http://dx.doi.org/10.1080/10826076.2010.489009