Quantitative analysis and pharmacokinetic study of phellopterin in rat plasma by UPLC-MS/MS

Abstract Phellopterin, a naturally derived furanocoumarin, is widely distributed in medicinal plants like Angelica dahurica and Toddalia asiatica , as well as in citrus fruits. In this experiment, an UPLC-MS/MS bioanalytical method over the concentration range of 0.725–290 ng mL −1 was established for the quantitative analysis and pharmacokinetic study of phellopterin in rat plasma. Following protein precipitation with acetonitrile, the samples were separated by gradient elution on a UPLC system, using acetonitrile-0.1% formic acid as the mobile phase. Quantification was performed using multiple reaction monitoring (MRM) method in electrospray positive-ion mode (ESI+), with the ion transitions of m / z 301.1 → 233.4 for phellopterin and m / z 209.1 → 194.1 for the internal standard, fraxetin. The accuracy of phellopterin ranged from 87.9 to 112.4%, with the precision between 4.1 and 12.2%. The matrix effect was 92.4–97.4%, and the recovery was over 77.9%. The optimized UPLC-MS/MS bioanalytical method was successfully used to study the pharmacokinetics of phellopterin in rats. The AUC (0−t) values were 74.2 ± 7.9 ng mL −1 *h for intravenous and 37.1 ± 5.3 ng mL −1 *h for oral administration, while the corresponding half-lives (t 1/2z ) were 1.1 ± 0.2 h and 3.1 ± 0.7 h, respectively. The bioavailability of phellopterin was determined to be 16.7%.