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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 determine the concentration of metformin hydrochloride in human plasma and study the pharmacokinetics in human. Methods: The plasma was treated with acetonitrile directly precipitated protein, the concentration of metformin hydrochloride was determined by a modified RP-HPLC method. The column was ZORBAX, SB-C18 (250 mm × 4 mm, 5 μm). The mobile phase was acetonitrile 0.005 mol·L -1 phosphate buffer (pH 3.5) (80:20) at a flow rate of 1. 2 ml · min-1, the detection wavelength was 240 nm. Blood concentration data using 3p97 software processing. Results: The linear range of metformin hydrochloride was 0.05-4 mg · L-1. The regression equation was Y = 0.083 99X-0.004 048 (r = 0.999 7). The average recoveries (%) of low, middle and high concentrations were 98.08 ± 1.25, 96.25 ± 0.98 and 94.68 ± 1.86, respectively. The relative recoveries were 100.77 ± 5.66 , 99.43 ± 3.19,99.75 ± 7.98, RSD≤3.43%, daytime RSD≤5.51%. The pharmacokinetic parameters were fitted to two-compartment model with the pharmacokinetic parameters 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. Conclusion: This method is simple, accurate and reproducible. The obtained pharmacokinetic parameters have reference value for the monitoring of clinical drug concentration.