Triapine is an inhibitor of ribonucleotide reductase (RNR). Studies have shown that triapine significantly decreases the activity of RNR and enhanced the radiation-mediated cytotoxicity in cervical and colon cancer. In this work, we have developed and validated a selective and sensitive LC-MS/MS method for the determination of triapine in human plasma. In this method, 2-[(3-fluoro-2-pyridinyl)methylene] hydrazinecarbothioamide (NSC 266749) was used as the internal standard (IS); plasma samples were prepared by deproteinization with acetonitrile; tripaine and the IS were separated on a Waters Xbridge Shield RP18 column (3.5 µm; 2.1 × 50 mm) using a mobile phase containing 25.0% methanol and 75.0% ammonium bicarbonate buffer (10.0 mm, pH 8.50; v/v); column eluate was monitored by positive turbo-ionspray tandem mass spectrometry; and quantitation of triapine was carried out in multiple-reaction-monitoring mode. The method developed had a linear calibration range of 0.250–50.0 ng/mL with correlation coefficient of 0.999 for triapine in human plasma. The IS-normalized recovery and the IS-normalized matrix factor of triapine were 101–104% and 0.89–1.05, respectively. The accuracy expressed as percentage error and precision expressed as coefficient of variation were ≤±6 and ≤8%, respectively. The validated LC-MS/MS method was applied to the measurement of triapine in patient samples from a phase I clinical trial.
Feng, Ye; Kunos, Charles A.; and Xu, Yan, "Determination of Triapine, A Ribonucleotide Reductase Inhibitor, In Human Plasma by Liquid Chromatography Tandem Mass Spectrometry" (2015). Chemistry Faculty Publications. 180.
This is the accepted version of the following article: Feng, Y.; Kunos, C. A.; Xu, Y. Determination of triapine, a ribonucleotide reductase inhibitor, in human plasma by liquid chromatography tandem mass spectrometry. Biomedical Chromatography 2015, 29, 1380-1387., which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/bmc.3434/full