Quantitation of a new macrolide in plasma by high performance liquid chromatography with tandem mass spectrometric detection: Comparison with electrochemical detection

A method involving high performance liquid chromatography with tandem mass spectrometric detection was developed to determine the concentration of a n ew macrolide derivative, ABT-229, in human plasma. The analyte was extracte d using liquid-liquid extraction with a mixture of ethyl acetate and hexane at basic pH. Detection was highly specific for the analyte of interest, as evidenced by the lack of interference in the chromatograms of drug-fi ee p lasma extracts. The lower limit of quantitation was 0.10 ng/mL based on 1 m L of extracted plasma. The linear calibration range of the procedure extend ed from 0.10 to 199 ng/mL. The method proved reliable and rugged; within-ru n and day-to-day relative standard deviations were less than 10%. The stabi lity of ABT-229 under frozen storage, room temperature, and freeze/thaw con ditions was found to be excellent. Plasma concentrations determined by the method were highly comparable with data obtained by electrochemical detecti on.