Journal
BIOMEDICAL CHROMATOGRAPHY
Volume 30, Issue 3, Pages 494-496Publisher
WILEY-BLACKWELL
DOI: 10.1002/bmc.3562
Keywords
5-azacytidine; DNA methyltransferase inhibitor; LC; MS; MS; pharmacokinetics
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Funding
- Celgene Corporation
- Flight Attendants Medical Research Institution (FAMRI) Center for Excellence at the Johns Hopkins University School of Medicine
- Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins [NIH] [P30 CA006973, UL1 TR001079]
- Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins [Shared Instrument Grant] [1S10RR026824-01]
- National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) [UL1 TR 001079]
- NIH Roadmap for Medical Research
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The DNA methyltransferase inhibitor 5-azacytidine is being evaluated clinically as an oral formulation to treat various solid tumors. A sensitive, reliable method was developed to quantitate 5-azacytidine using LC-MS/MS to perform detailed pharmacokinetic studies. The drug of interest was extracted from plasma using Oasis MCX ion exchange solid-phase extraction 96-well plates. Chromatographic separation was achieved with a YMC J'sphere M80 C-18 column and isocratic elution with a methanol-water-formic acid (15:85:0.1, v/v/v) mobile phase over a 7 min total analytical run time. An AB Sciex 5500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of 5-azacytidine. The assay range was 5-500 ng/mL and proved to be accurate (97.8-109.1%) and precise (CV 9.8%). Tetrahydrouridine was used to stabilize 5-azacytidine in blood/plasma samples. With the addition of tetrahydrouridine, long-term frozen plasma stability for 5-azacytidine at -70 degrees C has been determined for at least 323 days. The method was applied for the measurement of total plasma concentrations of 5-azacytidine in a cancer patient receiving a 300 mg oral daily dose. Copyright (c) 2015 John Wiley & Sons, Ltd.
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