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

摘要

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 × 150 mm, 3.5 μm) 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 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.