桑叶总生物碱中1-脱氧野尻霉素在大鼠体内的药物动力学研究

目的建立测定大鼠血浆中1-脱氧野尻霉素(DNT)含量的柱前衍生-高效液相色谱荧光法,初步研究桑叶总生物碱中DNJ在大鼠体内的药动学过程。方法大鼠灌胃桑叶总生物碱(给药剂量按DNJ计约为80 mg·kg-1)后不同时间点采集血样,采用柱前衍生-高效液相色谱荧光法测定,色谱条件为HiQSiL C18分析柱(4.6 mm×250 mm,5μm),乙腈-0.1%醋酸水溶液(40∶60,V/V)为流动相,荧光检测器激发波长254 nm,发射波长322 nm,流速1.0 mL·min-1,柱温25℃。DNJ血药浓度-时间数据用药动学软件3P97处理。结果 DNJ血浆浓度在1.4～22.4 mg·L-1线性关系良好,血浆中1-脱氧野尻霉素定量下限为1.4 mg·L-1。日内、日间精密度(RSD)分别为3.7%～5.8%和4.6%～6.0%,方法回收率为97.6%～101.5%,提取回收率为76.3%～81.6%。DNJ在大鼠体内的血药浓度-时间过程符合二房室模型,Ka=(4.85±0.95)h-1,AUC=(19.22±1.37)mg·h·L-1,Cmax=(12.98±1.92)mg·L-1,Tmax=(0.50±0.00)h。结论该法准确可靠,专属性强,适用于DNJ在大鼠体内的血药浓度测定及药代动力学研究。

Pharmacokinetics Studies on 1-Deoxynojirimycin from Total Alkaloids of Folium Mori in Rats

Objective To establish a fluorometric method based on pre-column derivatization by reversed-phase high performance liquid chromatography(HPLC)is described for the separation and quantification of 1-deoxynojirimycin in plasma,and to study its pharmacokinetics in rats.Methods The rats were orally treated with total alkaloids from the leaves of Morus alba L.,and then plasma samples were extracted with acetonitrile and the plasma concentration of 1-deoxynojirimycin was analyzed by fluorometric HPLC with pre-column derivatization.The analytes were separated on a HiQSiL C 18 column(4.6 mm × 250 mm,5 μm)using acetonitrile-0.1 % aqueous acetic acid(40 ∶ 60,V/V)as mobile phase at a flow rate of 1.0 mL.min-1.The excitation wavelength was 254 nm and the emission wavelength was 322 nm,the column temperature was 25 ℃.The pharmacokinetic parameters were calculated by the software of 3P97.Results A good linear relationship of 1-deoxynojirimycin was obtained in the range of 1.4 and 22.4 mg.L-1,the limit of quantitation was 1.4 mg.L-1.The intra-day precision and inter-day precision of this method were 3.7% to 5.8% and 4.6 % to 6.0 %,respectively.The method recoveries ranged from 97.6 % to 101.5%.The extraction recoveries ranged from 76.3 % to 81.6 %.The plasma 1-deoxynojirimycin concentration-time curve could be evaluated by two compartment model.The main pharmacokinetic parameters,such as K a,AUC,C max,and T max,were(4.85 ± 0.95)h-1,(19.22 ± 1.37)mg.h.L-1,(12.98 ± 1.92)mg.L-1,(0.50 ± 0.00)h,respectively.Conclusion The method has been successfully applied to the determination of 1-deoxynojirimycin in rat plasma.