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A sensitive and reliable method was developed to quantitate navitoclax in human plasma using liquid chromatography with tandem mass spectrometry with which to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of navitoclax and the internal standard, navitoclax\u2010d8, was achieved with a Waters Acquity UPLC BEH C<jats:sub>18<\/jats:sub> column using isocratic flow over a 3\u00a0min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of navitoclax. The assay range was 5\u20135,000\u2009ng\/ml and proved to be accurate (89.5\u2013104.9%) and precise (CV\u2009\u2264\u200911%). Long\u2010term frozen plasma stability for navitoclax at \u221270\u00b0C was at least 43\u2009months. 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