Pharmacokinetic Study of Icariside II After a Single Dose Administration of YiGu Capsule in Healthy Chinese Volunteers

Abstract

To investigate the pharmacokinetic characteristics of icariside II after a single oral dose administration of YiGu Capsule in healthy ­Chinese volunteers. 8 (4 female) healthy Chinese volunteers were involved and administrated for 15 doses of YiGu Capsule after fasting overnight. 4 ml of blood samples were collected at scheduled time before and after administration. Icariside II in human plasma was separated on a Agela Venusil XBP-C18 column (250 mm×4.6 mm, 5 μm), and eluted using acetonitrile-water (containing 0.1% formic acid) (70:30, V/V) as mobile phase. The analytes were detected with a ­triple quad HPLC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring mode were m/z 515.1 (precursor ion) to m/z 369.1 (product ion) for icariside II and m/z 321.0 (precursor ion) to m/z 275.0 (product ion) for lorazepam (internal standard).The plasma concentration of icariside II was determined by established HPLC-MS/MS method after disposition and its pharmacokinetic parameters were analyzed and evaluated by PK Solver Software (version 1.0). The C_max, T_max, t_1/2, AUC_0–24, AUC_0−∞, MRT_0−∞ ⁻¹, 2.50±1.91 h, 7.61±2.81 h, 12.68±4.86 ng · mL⁻¹ · h, 14.22±5.75 ng · mL⁻¹ · h, 9.55±1.56 h, 12.81±7.94 L · h⁻¹ and 121.70±32.70 L. The established HPLC-MS/MS method was sensitive, selective and rapid for icariside II pharmacokinetic study.

Key words

icariside II - LC-MS/MS - pharmacokinetics - human plasma

• References

• 1 Zhang D-W, Cheng Y, Wang N-L et al. Effects of total flavonoids and flavonol glycosides from Epimedium koreanum Nakai on the proliferation and differentiation of primary osteoblasts. Phytomedicine 2008; 15: 55-61
• 2 Ma H, He X, Yang Y et al. Hao and Zhengping Jia. The genus Epimedium: An ethnopharmacological and phytochemical review. Journal of Ethnopharmacology 2011; 134: 519-541
• 3 Xin H, Danyan Z, Yijia L. A novel anticancer agent, icaritin, induced cell growth inhibition, G1 arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells. European. Journal of Pharmacology 2007; 564: 26-36
• 4 Pan Y, Kong L, Xia X et al. Antidepressant-like effect of icariin and its possible mechanism in mice. Pharmacology Biochemistry and Behavior 2005; 82: 686-694
• 5 Sui H, Gao P, Xu H. The safety evaluation of herba Epimedii water extract. Carcinogenesis, Teratogenesis and Mutagenesis 2006; 18: 439-442
• 6 Ming S, Aimin C, Songsong Y et al. Determination of icariin in Epimedium Koreanum Nakai by high performance liquid chromatography. Chinese Journal of Chromatography 1999; 15: 166-167
• 7 Jian L, Yi-jia L. Determination of icariin and metabolites in rat serum by capillary zone electrophoresis: rat pharmacokinetic studies after administration of icariin. Journal of Pharmaceutical and Biomedical Analysis 2004; 36: 365-370
• 8 Liu JJ, Li SP, Wang YT. Optimization for quantitative determination of four flavonoids in Epimedium by capillary zone electrophoresis coupled with diode array detection using central composite design. Journal of Chromatography A 2006; 1103: 344-349
• 9 Yinhan G, See Chung Y, Sennappan KT et al. Trace analysis of icariin in human serum with dansyl chloride derivatization after oral administration of Epimedium decoction by liquid chromatography tandem mass spectrometry. Journal of Chromatography B 2007; 860: 166-172
• 10 Wen X, Yaping Z, Ming Y et al. LC–MS/MS method for the simultaneous determination of icariin and its major metabolites in rat plasma. Journal of Pharmaceutical and Biomedical Analysis 2007; 45: 667-672
• 11 Liu X, Wang Y, Wang B et al. Studies on the metabolism of icariin by intestinal bacteria. Chinese Traditional and Herbal Drugs 2000; 31: 834-837
• 12 Feng Q, Yingjie C, Yoshihiro K et al. Yoshihiro and . Metabolism of orally administered icariin in rats. Acta Pharmaceutica Sinica 1999; 34: 222-226
• 13 Ye L, Chen J, Liu S et al. Pharmacokinetics of icariin in rats. Chinese Pharmacuetical Journal 1999; 34: 33-36
• 14 Yong Z, Meirong H, Jianping Z et al. PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Computer Methods and Programs in Biomedicine 2010; 99: 306-314