Development and Validation of a Gas Chromatography-Mass Spectrometry Method for the Determination of Imperatorin in Rat Plasma and Tissue: Application to Study Its Pharmacokinetics

Abstract

A rapid and sensitive assay for the quantification of imperatorin in plasma and tissues has been developed. An analysis was performed by gas chromatography/mass spectrometry in the selected ion-monitoring mode. The main pharmacokinetic parameters obtained were T_max = 1.23 ± 0.26 h, C_max = 0.95 ± 0.38 µg/mL, AUC = 3.42 ± 0.52 h µg/mL and K_a = 1.34 ± 0.18 h. The experimental results showed that imperatorin was easily absorbed, but its elimination was slow, from 3 to 12 h after oral administration. The concentrations of imperatorin in rat liver, kidney, lung, and heart were higher than those in other organs. To determine the free fraction in serum, samples were filtered using ultrafiltration membranes with a molecular weight cut-off of 10 kDa, and extracted using liquid–liquid extraction. The protein binding values in rat plasma, spontaneous hypertensive rat plasma, human plasma and human serum albumin were 84 ± 3, 69 ± 7, 81 ± 7 and 75 ± 3%, respectively.