摘要

In this study, a simple, rapid and sensitive high performance liquid chromatography (HPLC) method is developed for the determination of ibrutinib in rabbit plasma samples using vortioxetine as the internal standard (IS). Sample preparation was accomplished through one-step liquid-liquid extraction with ethyl acetate, and chromatographic separation was carried out on an Agilent ZORBAX SB-C18 (4.6 x 125 mm, 5 mu m) at 35 degrees C. Mobile phase composed of a mixture of acetonitrile-0.1% trifluoroacetic acid-water (43: 27: 30) at a flow rate of 1.0 mL/min. Wavelength was set at 258 nm. The chromatographic retention times of ibrutinib and IS were 5.07 and 6.06 min, respectively. The lower limit of quantitation (LLOQ) was 5.0 ng/mL, and no interferences were detected in the chromatograms. The devised HPLC method was validated by evaluating its intra-and inter-day precisions and accuracies in a linear concentration range between 5.0 and 500 ng/mL. The method has also been successfully applied to a pharmacokinetic study of ibrutinib in rabbits for the first time, which provides the basis for the further development and application of ibrutinib.