Simultaneous determination and pharmacokinetic study of polygalaxanthone ill, tenuifolin, tenuifoliside A and tenuifoliside C in rat plasma by LC-MS/MS after oral administration

摘要

For the first time, a rapid and specific LC-MS/MS method has been developed for the simultaneous analysis of polygalaxanthone III, tenuifolin, tenuifoliside A and tenuifoliside C in rat plasma, and was applied to the pharmacokinetics (PK) studies of those three compounds. The analysis was carried out on an Agilent Eclipse plus C_(18) reversed-phase column (100 x 4.6 mm, 3.5 nm) by gradient elution with methanol and ammonia (0.01%, v/v). The flow rate was 0.4 mL min~(-1). All analytes including internal standards (I.S.) were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for polygalaxanthone III and tenuifoliside A ranging from 1 to 2000 ng mL~(-1), and tenuifolin and tenuifoliside C ranging from 2.5 to 2000 ng mL"1. The intra-day and inter-day precisions (RSD) were less than 12.98% and 7.50% respectively. The extraction recovery ranged from 70.06 ± 6.33% to 86.95 ± 5.35%, and I.S. was 77.23 ± 3.68%. Stability studies showed that the accuracies of polygalaxanthone III, tenuifolin, tenuifoliside A and tenuifoliside C ranged from 93.18% to 106.70%. The matrix effects ranged from 91.72 ± 4.80 to 101.84 ± 5.04. The validated method was successfully used to determine the concentration-time profiles of polygalaxanthone ill, tenuifolin, tenuifoliside A and tenuifoliside C.