UPLC-TQ/MS Determination and Pharmacokinetic Study of Eight Compounds in Normal and Lps-primed Rat Plasma after Oral Administration of Psoralea Fructus ethanol Extract

Background: Psoralea Fructus (PF) is one of the most frequently applied tonic Chinese herbs with various bioactivities, while recently, the idiosyncratic drug‑induced liver injury (IDILI) nature of PF was addressed, and liver injury cases were reported in the clinic. Our previous research indicated that many constituents exerted liver injury property, whereas the pharmacokinetic profile of these compounds between normal and immune stress states is still unclear.Objectives: This study aims to construct a validated method to simultaneously determine eight analytes (including psoralen, isopsoralen, psoralidin, corylin, psoralenoside, isopsoralenoside, bavachin, and neobavaisoflavone) in PF via UPLC‑TQ/MS, and to compare their pharmacokinetic properties in normal and LPS‑stimulated rats. Materials and Methods: The rats were randomly divided into four groups. The blood samples of different groups were harvested at different time points; the eight analytes were analyzed under UPLC‑TQ/MS, and the constructed method was confirmed in terms of specificity, linearity, lower limit of quantitation (LLOQ), precision, accuracy, stability, recovery, and matrix effect. Results: The developed UPLC‑TQ/MS method showed good linearity (r = 0.9972–0.9994) and specificity; the recovery and matrix effect were acceptable (ranging from 64.75 ± 1.59% to 104.31 ± 3.38%, and from 87.11 ± 1.91% to 115.45 ± 1.63%, respectively), the intra‑ and inter‑day precision of eight analytes were under 13.42%, the intra‑ and inter‑day accuracy was eligible (92.68%–108.85%), and the analytes were stable under storage conditions. All eight analytes in PFE were rapidly absorbed into the circulation, while the relevant pharmacokinetic parameters (including AUC, MRT, VRT, λ, V, t1/2, Cmax, Tmax, and CL) of these analytes were quite different between the normal and model rats. Conclusion: A sensitive, accurate, and rapid method was successfully established and validated to determine the plasma characteristics of analytes in normal and LPS‑primed rats. The pharmacokinetic profile indicated the body states might appreciably impact the pharmacokinetic profile of the bioactive constituents of PF, further inducing liver injury in specific patients.