title: Determination of triapine, a ribonucleotide reductase inhibitor, in human plasma by liquid chromatography tandem mass spectrometry.
abstract: 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.
authors: Department of Chemistry, Cleveland State University, 2121 Euclid Ave, Cleveland, OH, 44115, USA.
authors: Ye
authors: Y
authors: Feng
authors: Case Comprehensive Cancer Center, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH, 44106, USA.
authors: Charles A
authors: CA
authors: Kunos
authors: Department of Chemistry, Cleveland State University, 2121 Euclid Ave, Cleveland, OH, 44115, USA.|Case Comprehensive Cancer Center, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH, 44106, USA.
authors: Yan
authors: Y
authors: Xu
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood*; D006801:Humans; D011725:Pyridines / Q000097:blood*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013882:Thiosemicarbazones / Q000097:blood*
chemical_list: D004791:Enzyme Inhibitors; D011725:Pyridines; D013882:Thiosemicarbazones; C078157:3-aminopyridine-2-carboxaldehyde thiosemicarbazone; D012264:Ribonucleotide Reductases
keywords: LC-MS/MS; human plasma; method validation; ribonucleotide reductase inhibitor; triapine