LC-MS/MS Assay Validation for a New Immune Modulator, JHL45, and its Major Metabolite in Plasma: Application to Pharmacokinetic Studies in Rats

摘要

JHL45, a novel immune modulator for anti-atopic dermatitis and allergic airway disease, was synthesized from decursin isolated from Angelica gigas. In order to conduct a pharmacokinetic study of JHL45, an analytical method, ideally one that uses a minimal amount of biological sample must first be validated. In this study, a HPLC-MS/MS method was developed and validated for the quantification of JHL45 and its major metabolite, (+)-decursinol, from 10 μL of rat plasma. JHL45 was stable under the analysis conditions, and intra- and inter-day accuracies exceeded 90.06%, with a precision variability ≤ 13.16% for each analyte. The mean values for C_(max), AUC_(8h), half-life of JHL45 in rats after intravenous administration of 5 mg/kg JHL45 were 24.59 μg/mL, 10.02 μg·h/mL, and 1.88 h, respectively. The validated method herein will be useful for further pharmacokinetic studies of JHL45, as well as in preclinical and clinical phases.