Quantification of Meranzin Hydrate in Rat Hippocampus and Plasma by LC-MS/MS: A Compound Derived from Chaihu-Shugan-San Displays Antidepressant Potential

摘要

Meranzin hydrate (MH), a compound derived from Chaihu-Shugan-San (CSS), displayed potent preclinical antidepressant functions. In this study, an LC-MS/MS method was developed and validated to quantify the MH in rat hippocampus and plasma. Tert-butyl methyl ether and irbesartan were used as the extraction reagent and the internal standard (IS), respectively. Chromatographic separation was achieved on a C-18 column using the mobile phase, which consisted of a 20 mM solution of ammonium formate and acetonitrile at a ratio of 60:40. The flow rate was set at 0.3 mL min(-1). The detection was performed by multiple reactions monitored in a positive ion mode via electrospray ionization. The transitions were monitored by m/z 279.1 -> 188.9 for MH and m/z 429.0 -> 206.9 for IS. Linear calibration curves were obtained in the concentration range of 0.70-278.29 ng mL(-1), with a lower limit of quantification of 0.70 ng mL(-1). The intra- and inter-day precision values were below 11.9 % relative standard deviation, and the accuracy was from 90.5 to 107.5 %. The recovery was from 85.7 to 89.5 %. The LC-MS/MS method was applied to quantify the MH in hippocampus tissue compared with that in plasma after intragastric administration of MH (9 mg kg(-1)) to rats. The results showed that the AUC((0-480)), AUC((0-infinity)), and C (max) values of MH in plasma were much higher than those values in the hippocampus of rats. Our study established a sensitive, reliable, and specific LC-MS/MS method for quantification of MH and confirmed the existence of MH in the rat hippocampus, which may contribute to antidepression mechanism research for MH in further study.