摘要
目的:测定人血浆中盐酸二甲双胍的浓度,并进行人体药动学研究。方法:血浆用乙腈直接沉淀蛋白处理后,用改进的RP-HPLC法检测盐酸二甲双胍的浓度。色谱柱为ZORBAX,SB-C18(250 mm×4 mm,5μm);流动相为乙腈0．005 mol·L-1-磷酸缓冲液(pH 3．5)(80∶20),流速为1．2 ml·min-1,检测波长为240 nm。血药浓度数据用3p97软件进行处理。结果:盐酸二甲双胍的线性范围为0．05～4 mg·L-1,回归方程为Y=0．083 99X-0．004 048(r=0．999 7)。低、中、高三种浓度的绝对回收率(％)分别为98．08±1．25,96．25±0．98,94．68±1．86,相对回收率分别为100．77±5.66,99．43±3．19,99．75±7．98,日内RSD≤3．43％,日间RSD≤5．51％。药时曲线经拟合,符合二室模型,主要药动学参数为Ke=0．44±0．12 h-1,t1/2β= 1．56±0．34 h,AUC=11 319．87±4560 mg·h-1·L-1,CL=113．19±23．45 L·h-1,Vd=253．95±62．74 L,tmax=1．79±0．35 h, Cmax=1．78±0．46 mg·L-1。结论:本法操作简便,结果准确,重现性好。所得药物动力学参数对临床药物浓度监测具有参考意义。
Objective： To establish a RP-HPLC method for the determination the content of metformin hydrochloride in human plasma and study its pharmacokinetics. Method： After protein sediment by acetonitrile, the concentration of metformin hydrochloride in plasma was determined by a RP-HPLC. The ZORBAX,SB-C18 column（250 mm×4 mm,5μm）was used. The mobile phase was acetonitrile- 0.01 mol·L^-1 potassium bihydrogen phosphate buffer solution （80： 20） , the flow rate was 1.2ml·min^-1. The detection wavelength was 240 nm. The data of concentration-time were analyzed by 3p97 pharmacokinetic software. Result： The linear range of the calibration was 0.05 - 4 mg·L^-1 with regressive equation of Y = 0. 08399X - 0. 004 048 （ r = 0. 999 7 ）. The absolute recovery rate （ % ） of low, medium and high concentration was 98.08±1.25, 96.25±0.98 and 94.68±1.86, respectively. The relative recovery rate （ % ） was 100.77± 5.66,99.43± 3.19 and 99.75± 7.98, respectively. Within-day RSD was ≤3.43 % , Between-day RSD was ≤5.51%. The main pharmacokinetic parameters were as follows： Ke = 0.44 ± 0.12 h^-1, t1/2β = 1.56±0.34 h ,AUC = 11319.87±4560 mg·h^-1·L^-1 ,CL= 113.19±23.45 L·h^-1 ,Vd =253.95±62.74 L,tmax= 1.79±0.35 h,Cmax = 1.78±0.46 mg·L^-1. Conclusion： The analyzing method was simple and accurate. The pharmacokinetic parameters could guide the monitoring of metformin hydrochloride concentration in the clinic setting.
出处
《中国药师》
CAS
2006年第10期935-937,共3页
China Pharmacist
