摘要
目的研究新补骨脂异黄酮在大鼠体内的药动学及组织分布。方法分析采用Waters ACQUITYTMBEH C18色谱柱(2.1 mm×100 mm,1.7μm);流动相水(含0.1%甲酸)-乙腈(含0.1%甲酸),梯度洗脱;体积流量0.4 m L/min;柱温40℃;电喷雾离子源(ESI);正离子模式;多反应监测模式扫描。超高效液相色谱串联三重四级杆质谱(UPLC-MS/MS)法测定大鼠血清、肾、肝、小肠中新补骨脂异黄酮含有量,计算主要药动学参数,绘制血药浓度-时间曲线。结果大鼠血清和组织中新补骨脂异黄酮在4.0~700.0 ng/m L范围内线性关系良好(R2≥0.995 0),基质效应81.6%~112.4%,回收率95.9%~106.4%。随着给药剂量(50、100、200 mg/kg)增加,t1/2、tmax、Cmax、AUC0~t、AUC0~∞、MRT0~t、MRT0~∞升高(P<0.05);给药剂量为100 mg/kg时,新补骨脂异黄酮含有量在肾中最高,肝中次之。结论新补骨脂异黄酮在大鼠体内吸收较慢,消除半衰期长,肾、肝中有药物蓄积。
AIM To study the pharmacokinetics and tissue distribution of neobavaisoflavone in rats in vivo.METHODS The analysis was performed on a 40℃thermostatic Waters ACQUITYTM BEH C18 column(2.1 mm×100 mm,1.7μm),with the mobile phase comprising of water(containing 0.1%formic acid)-acetonitrile(containing 0.1%formic acid)flowing at 0.4 mL/min in a gradient elution manner.Electrospray ionization(ESI)was scanned in a positive ion mode with multiple reaction monitoring.Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was adopted in the content determination of neobavaisoflavone in rat serum,kidney,liver and small intestine,after which main pharmacokinetic parameters were calculated,and plasma concentration-time curves were drawn.RESULTS Neobavaisoflavone showed good linear relationships within the range of 4.0-700.0 ng/mL in rat serum and tissues(R2≥0.9950),whose matrix effects and recoveries were81.6%-112.4%and 95.9%-106.4%,respectively.With the increase of administration dosage(50,100,200 mg/kg),t1/2,tmax,Cmax,AUC0-t,AUC0-∞,MRT0-t and MRT0-∞were elevated(P<0.05).At the administration dosage of 100 mg/kg,neobavaisoflavone content was the highest in kidney,while that in liver took the second place.CONCLUSION Neobavaisoflavone demonstrates slow absorption,long elimination half-life,and drug accumulation in kidney and liver in rats in vivo.
作者
张志超
王小康
潘远安
刘江红
ZHANG Zhi chao;WANG Xiao kang;PAN Yuan an;LIU Jiang hong(Department of Pharmacy,Shenzhen Longhua District Central Hospital,Shenzhen 518110,China)
出处
《中成药》
CAS
CSCD
北大核心
2020年第4期825-830,共6页
Chinese Traditional Patent Medicine
基金
广东省中医药管理局项目(2182131)
深圳市龙华区科技创新项目(2017032)。
作者简介
张志超(1985—),男,主管药师,从事药理学研究。Tel:(0755)28016178,E mail:823493971@qq.com;通信作者:刘江红(1966—),女,副主任药师。Tel:(0755)28016178,E mail:lhzxyyyxb@163.com。
