title: An alternative liquid chromatography-mass spectrometric method for the determination of azithromycin in human plasma and its application to pharmacokinetic study of patients with malaria.
abstract: 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 minutes, 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/minute. Chromatographic analysis was carried out at 25 degrees C. Sample preparation was 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 intra-day and inter-day assays. The limit of quantification was acceptable at 0.5 ng using 200 microl 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 5 Thai male patients with acute uncomplicated falciparum malaria.
authors.affiliation: Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University (Rangsit Campus), Pathum Thani, Thailand.
authors.forename: Anuruk
authors.initials: A
authors.lastname: Choemunng
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000188:drug therapy; D015203:Reproducibility of Results; D015575:Roxithromycin / Q000737:chemistry / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000900:Anti-Bacterial Agents; D015575:Roxithromycin; D017963:Azithromycin