Validation and implementation of a liquid chromatography/tandem mass spectrometry assay to quantitate ABT-751, ABT-751 glucuronide, and ABT-751 sulfate in human plasma for clinical pharmacology studies.

A method has been developed for the quantitation of ABT-751, ABT-751 glucuronide, and ABT-751 sulfate in human plasma. ABT-751 and metabolites were separated from endogenous material on a C18 column with acetonitrile-ammonium acetate (2 mM) mobile phase containing formic acid (0.1%, v/v) using isocratic flow for 5 min. The analytes were monitored by tandem-mass spectrometry. Calibration curves were generated over the range of 20-5,000 ng/ml for ABT-751, ABT-751 glucuronide, and ABT-751 sulfate. A 20,000 ng/ml sample that was diluted 1:10 (v/v) with plasma was accurately quantitated. The method has been successfully applied to study the plasma pharmacokinetics of ABT-751 in humans.