Du Chenhui, Yan Yan, Shen Chenxi, Cui Xiaofang, Pei Xiangping, Qin Xuemei
School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan, 030619, China.
Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, China.
J Pharm Anal. 2020 Aug;10(4):385-395. doi: 10.1016/j.jpha.2020.03.003. Epub 2020 Mar 4.
Ziziphi Spinosae Semen (ZSS), a traditional Chinese medicine, is used in clinics for the treatment of insomnia in China and other Asian countries. Herein, we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control (NC) and -chlorophenylalanine (PCPA)-induced insomnia model (IM) rats that were orally administered the aqueous extract of ZSS. An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass (UHPLC-Q-Orbitrap-MS) method was developed and validated for the simultaneous determination of coclaurine, magnoflorine, spinosin, 6-feruloylspinosin, jujuboside A (JuA), and jujuboside B (JuB) in ZSS in rat plasma. The established approach was successfully applied to a comparative pharmacokinetic study. The systemic exposures of spinosin and 6-feruloylspinosin were decreased in the IM group compared to the NC group, while plasma clearance (CL) was significantly increased. The T values of JuA and JuB in IM rats were significantly lower than those in NC rats. The T of JuA in the IM group was significantly accelerated. The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups. These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin, 6-feruloylspinosin, JuA, and JuB in the ZSS aqueous extract, providing an experimental basis for the role of ZSS in insomnia treatment. The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS.
酸枣仁是一种传统中药，在中国和其他亚洲国家的临床中用于治疗失眠。在此，我们首次描述了在正常对照（NC）大鼠和对氯苯丙氨酸（PCPA）诱导的失眠模型（IM）大鼠中口服酸枣仁水提取物后，对酸枣仁六种主要化合物的比较药代动力学研究。建立并验证了一种超高效液相色谱-四极杆轨道阱质谱（UHPLC-Q-Orbitrap-MS）方法，用于同时测定大鼠血浆中酸枣仁中的荷叶碱、木兰碱、斯皮诺素、6-阿魏酰斯皮诺素、酸枣仁皂苷A（JuA）和酸枣仁皂苷B（JuB）。所建立的方法成功应用于比较药代动力学研究。与NC组相比，IM组中斯皮诺素和6-阿魏酰斯皮诺素的全身暴露量降低，而血浆清除率（CL）显著增加。IM大鼠中JuA和JuB的T值显著低于NC大鼠。IM组中JuA的T显著加快。两组间荷叶碱和木兰碱的药代动力学参数没有明显影响。这些结果表明，失眠的病理状态改变了酸枣仁水提取物中斯皮诺素、6-阿魏酰斯皮诺素、JuA和JuB的血浆药代动力学，为酸枣仁在失眠治疗中的作用提供了实验依据。因此，基于比较药代动力学的UHPLC-Q-Orbitrap-MS全扫描模式可为筛选作为酸枣仁质量标志物的潜在有效物质提供可靠且合适的手段。
