Determination of SYUIQ-F5, a Novel Telomerase Inhibitor and Anti-tumor Lead-Compound, in Tissues and Plasma Samples by LC–MS–MS: Application to a Tissue Distribution Study in Rat

Abstract

A sensitive assay for determining SYUIQ-F5, a novel telomerase inhibitor and anti-tumor drug, in rat tissues and plasma was developed and validated by using liquid chromatography/tandem mass spectrometry (LC-MS-MS). After a single step liquid-liquid extraction with ethyl acetate-dichloromethane, SYUIQ-F5 and SUCL (internal standard) were subjected to LC-MS-MS analysis using positive electro-spray ionization under selected reaction monitoring mode. Chromatographic separation of SYUIQ-F5 and SUCL was achieved on a Zorbax Eclipse Plus C18 column (I.D. 4.6 mm 9 150 mm, 3.5 lm) with a mobile phase consisting of acetonitrile-2 mM ammonium formate (90:10, v/v) at a flow rate of 0.6 mL min -1 . The intra-and inter-batch precision of the method were \12.2 and 8.7%, respectively. The intra-and inter-batch accuracies ranged from 100.2 to 107.3%. The lowest limit of quantification for SYUIQ-F5 was 0.5 ng mL -1 . The method was applied to a SYUIQ-F5 tissue distribution study after an oral dose of 30 mg kg -1 to rats. SYUIQ-F5 tissue concentrations decreased in the order of small intestine [ liver[ lung[ spleen[ stomach[ kidneys[ heart[ brain[ muscle[ fat[ testes[ plasma. SYUIQ-F5 could still be detected in most of the tissues at 48-h post-dosing. These results indicated that the LC-MS-MS method was sensitive, reliable, and specific to quantify SYUIQ-F5 in different rat tissues.