A robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of 5-azacytidine

作者：Anders Nicole M; Wanjiku Teresia M; He Ping; Azad Nilofer S; Rudek Michelle A^*

来源：Biomedical Chromatography, 2016, 30(3): 494-496.

DOI：10.1002/bmc.3562

• 5-azacytidine
• DNA methyltransferase inhibitor
• LC
• MS
• MS
• pharmacokinetics

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.

• 出版日期2016-3