UFLC method development and validation of a novel triethylamine containing thiophene S006-830-an antitubercular molecule and its application to pharmacokinetic and bioavailability studies in SD rats

摘要

A sensitive and selective ultra fast liquid chromatography (UFLC) method has been developed and validated for the determination of a potent and novel antitubercular compound S006-830 in Sprague Dawley (SD) rat plasma. Samples were extracted and processed by protein precipitation method using acetonitrile. Chromatographic separation was achieved on a Phenomenex, Luna C-18 column (3m, 100mm x 2mm i.d.) under isocratic condition. Detection was performed on UFLC-NEXERA system (LC-30AD, Shimadzu, Kyoto, Japan) with a degasser (DGU-20A), auto-injector (SIL-30AC), fixed with a 100-L loop. Method was found sensitive and reproducible over a linearity range of 15.6-2000 ng/mL. Recovery of S006-830 and internal standard was found >90% for spiked matrix control and standard quality control plasma samples. This validated method was successfully applied to generate pharmacokinetic profile of S006-830 in SD rats. Oral dose proportionality studies were conducted at 100, 50, 25 mg/Kg dose levels, while an IV study was conducted at 25 mg/Kg dose. There was dose dependent increase in AUC and C-max indicating S006-830 to exhibit linear pharmacokinetics. S006-830 exhibited favorable bioavailability in the range of 45-55%. Copyright (c) 2014 John Wiley & Sons, Ltd.