LC-MS/MS determination and pharmacokinetic study of four lignan components in rat plasma after oral administration of Acanthopanax sessiliflorus extract.

Background: Acanthopanax sessiliflorus (Rupr. et Maxim.) Seem. is a shrub mainly present in China, Japan and Korea, the root bark of which is considered as one of the sources of Wujiapi and widely used for its various pharmacological effects.

Objective: A selective and sensitive UPLC-MS/MS method was developed and validated for the determination and pharmacokinetic study of asarinin, sesamin, helioxanthin and savinin in rat plasma.

Methods: Sample preparation involved a liquid-liquid extraction of the analytes with methyl tert-butyl ether (MTBE). LC separation was achieved on a UPLC C(18) column at 30°C with a mobile phase consisting of methanol-2 mM ammonium acetate (68:32, v/v). The detection was accomplished by multiple-reaction monitoring (MRM) scanning with electrospray ionization (ESI) source operating in the positive ionization mode. The optimized mass transition ion-pairs (m/z) monitored for asarinin, sesamin, helioxanthin, savinin and IS were 372.2/233.0, 372.2/233.0, 349.1/319.0, 352.9/334.9 and 180.0/109.7, respectively.

Results: The current LC-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability and was suitable for pharmacokinetic studies of the four lignans after oral administration of Acanthopanax sessiliflorus extract. The time to reach the maximum plasma concentration (T(max)) was 2.50±0.15 h for asarinin, 1.94±0.28 for sesamin, 2.22±0.48 h for helioxanthin and 2.83±0.29 h for savinin. The elimination half-time (t(1/2)) of asarinin, sesamin, helioxanthin and savinin was 6.08±1.10, 11.69±0.50, 7.16±0.52 and 6.26±0.57 h, respectively.

Conclusions: This paper described a simple, sensitive and validated UPLC-MS/MS method for simultaneous determination of four lignans in rat plasma after oral administration of Acanthopanax sessiliflorus extract, and investigated on their pharmacokinetic studies as well.