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目的:建立一种简单快速测定人血浆中格列喹酮浓度的高效液相色谱法,并用于格列喹酮片的药动学研究。方法:采用乙腈直接蛋白沉淀法处理血浆样本,建立高效液相色谱-荧光检测法测定血浆样本中格列喹酮的浓度。流动相为乙腈-20mmol·L-1磷酸二氢钾(80∶20,v/v,pH 2.5),流速为1.0 ml·min-1。荧光检测器:激发波长315 nm,发射波长410 nm。结果:血浆格列喹酮浓度在0.034~2.2μg·ml-1范围内呈良好的线性,定量下限为0.034μg·ml-1。方法回收率99.23%~108.11%,提取回收率85.78%~88.77%,日内、日间精密度均<10%,特异性、稳定性考察均符合要求。应用本法测定20名健康受试者单次口服60 mg格列喹酮片的血浆药物浓度并计算主要药动学参数,变异系数均接近或大于50%。结论:该方法简便快速、灵敏度高,可用于大批量测定格列喹酮的血药浓度;格列喹酮药动学参数的个体差异较大,临床需注意个体化用药。
Objective: To establish a simple and rapid determination of gliquidone concentration in human plasma by high performance liquid chromatography, and for gliquidone tablets pharmacokinetic study. Methods: The plasma samples were treated with acetonitrile direct protein precipitation, and the concentration of gliquidone in plasma samples was determined by high performance liquid chromatography with fluorescence detection. The mobile phase consisted of acetonitrile-20 mmol·L-1 potassium phosphate monobasic (80:20, v / v, pH 2.5) at a flow rate of 1.0 ml · min-1. Fluorescence detector: excitation wavelength 315 nm, emission wavelength 410 nm. Results: The plasma concentration of gliquidone in the range of 0.034 ~ 2.2μg · ml-1 showed a good linearity with a lower limit of quantitation of 0.034μg · ml-1. The recoveries were 99.23% -108.11% and the recoveries were 85.78% ~ 88.77%. The precision of intra-day and inter-day were all less than 10%. The specificity and stability of the method met the requirements. This method was used to determine plasma concentrations of 20 mg gliclazide tablets in 20 healthy subjects and to calculate the main pharmacokinetic parameters with coefficients of variation close to or greater than 50%. Conclusion: The method is simple, rapid and sensitive. It can be used to determine the plasma concentration of gliquidone in large quantities. Individuals with different pharmacokinetic parameters of gliquidone may need individual attention in clinic.