SIMULTANEOUS HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY ANALYSIS OF AZITHROMYCIN AND 2 OF ITS METABOLITES IN HUMAN TEARS AND PLASMA

This article describes a high-performance liquid chromatographic (HPLC ) method for the measurement of azithromycin (AZI) and two of its meta bolites, 9a-N-desmethylazithromycin (ADES) and N-desmethylazithromycin (NDES), in human tears and plasma. The drug, metabolites, and interna l standard (n-propylazithromycin [IS]) were detected electrochemically after injection of the extracted sample into the HPLC system. The pea k height ratio (AZI, ADES, or NDES to IS) varied linearly, with concen trations in the ranges of 0.1 mg/L to 2.0 mg/L (tears) and 0.01 mg/L t o 2.0 mg/L (plasma) of Au, ADES, and NDES; the correlation coefficient (r) was more than 0.994 mg/L for all of the compounds (n = 6). The an alysis of tear samples collected at different intervals within 12 hour s to 144 hours after a dose of 20 mg/kg of AZI from a trachoma patient yielded concentrations ranging from 1.52 mg/L to 0.34 mg/L for AZI, 0 .79 mg/L to 0.27 mg/L for ADES, and 1.99 mg/L to less than 0.20 mg/L f or NDES. The concentration of AZI in plasma ranged from 0.15 mg/L to 0 .01 mg/L, whereas ADES and NDES were undetectable.