Huang Zhen-Wu, Yang Yue-Xin, Huang Ling-He, Zhang Shuang-Qing
National Institute for Nutrition and Health Chinese Center for Disease Control and Prevention Beijing China.
Woods Worth College University of Toronto Toronto ON Canada.
Food Sci Nutr. 2019 Nov 12;7(12):4001-4006. doi: 10.1002/fsn3.1263. eCollection 2019 Dec.
Icaritin (ICT) has distinct bioactivities, especially known for its beneficial effects on bone-related degenerative disorders; however, its pharmacokinetic properties remain unknown. A novel developed UPLC-MS/MS method for the determination of ICT and its main metabolite glucuronidated icaritin (GICT) was firstly applied to pharmacokinetic and metabolism studies of ICT in female rats, which were intraperitoneally given 40 mg/kg ICT. Following the protein precipitation of plasma samples with acetonitrile, ICT and GICT were separated on a C18 column using gradient elution mode and quantified in the multiple reaction monitoring mode. The linearities were acceptable for ICT ( = 0.9960) and GICT ( = 0.9968), and the lower limit of quantification values was 0.5 and 5 ng/ml, respectively. The accuracy fell in the range of 92.0%-103.1% and precisions were within 9.5%. Good linearity, accuracy, precision, and recovery were achieved for the UPLC-MS/MS method. ICT was predominantly and rapidly biotransformed to GICT which was slowly eliminated in vivo with a terminal half-life value of 4.51 hr. Pharmacokinetics of pure ICT eliminated biotransformation interference of extract and disclosed genuine pharmacokinetic manner of ICT, as well as firstly elucidated low concentration and bioavailability of ICT in rat plasma.
淫羊藿素（ICT）具有独特的生物活性，尤其以其对骨相关退行性疾病的有益作用而闻名；然而，其药代动力学性质尚不清楚。一种新开发的用于测定ICT及其主要代谢产物葡萄糖醛酸化淫羊藿素（GICT）的超高效液相色谱-串联质谱（UPLC-MS/MS）方法首次应用于腹腔注射40mg/kg ICT的雌性大鼠的ICT药代动力学和代谢研究。血浆样品用乙腈进行蛋白沉淀后，ICT和GICT在C18柱上采用梯度洗脱模式进行分离，并在多反应监测模式下进行定量。ICT（r = 0.9960）和GICT（r = 0.9968）的线性关系良好，定量下限值分别为0.5和5 ng/ml。准确度在92.0%-103.1%范围内，精密度在9.5%以内。UPLC-MS/MS方法具有良好的线性、准确度、精密度和回收率。ICT主要迅速生物转化为GICT，GICT在体内消除缓慢，终末半衰期值为4.51小时。纯ICT的药代动力学消除了提取物的生物转化干扰，揭示了ICT真正的药代动力学方式，并首次阐明了ICT在大鼠血浆中的低浓度和生物利用度。
