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Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of navitoclax |
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| Authors: | Susan C Scott Nicole M Anders Ping He Avelina Hemingway Steven D Gore Christine L Hann Michelle A Rudek |
| Institution: | 1. Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, USA;2. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, USA;3. IDB/CTEP/NCI, National Cancer Institute, Rockville, Maryland, USA;4. Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA |
| Abstract: | The Bcl-2 family small molecule inhibitor navitoclax is being clinically evaluated to treat multiple cancers including lymphoid malignancies and small cell lung cancer. 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-d8, was achieved with a Waters Acquity UPLC BEH C18 column using isocratic flow over a 3 min 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 5–5,000 ng/ml and proved to be accurate (89.5–104.9%) and precise (CV ≤ 11%). Long-term frozen plasma stability for navitoclax at ?70°C was at least 43 months. The method was applied for the measurement of total plasma concentration of navitoclax in a patient receiving a 250 mg daily oral dose. |
| Keywords: | navitoclax quantitative analysis tandem mass spectrometry validation |