目的 建立高效液相色谱法测定血浆中替考拉宁(TEIC)总浓度(Ct)和游离浓度(Cf)的方法。方法 游离浓度血浆样本经超滤离心管处理后进行HPLC分析。采用C18色谱柱,以乙腈-0.01 mol·L-1磷酸二氢钠(25∶75,磷酸调pH值至3.3)为流动相,检测波长240 nm,柱温35 ℃,流速1.0 mL·min-1,考察该方法的专属性、标准曲线、定量下限、精密度、回收率和稳定性。结果 游离浓度在0.5~50 μg·mL-1内线性关系良好(y=12 801x-2 574.1,r2=0.999 8),定量下限为0.5 μg·mL-1,方法回收率为94.63%~103.72%,批内、批间RSD均<4.00％;总质量浓度在1.562 5~100 μg·mL-1内线性关系良好(y=10 576x+9 950.1,r2=0.999 8),定量下限为1.562 5 μg·mL-1,方法回收率为94.55%~99.59%,批内、批间RSD均<4.00％。在室温放置10 h、冻融循环3次和4 ℃冷藏72 h稳定性良好。结论 本方法简便、准确、灵敏,适用于临床替考拉宁血药总浓度和游离浓度的检测及药动学的研究。
Abstract
OBJECTIVE To establish an HPLC method for the determination of total(Ct) and free(Cf) concentrations of teicoplanin (TEIC) in plasma. METHODS For determing the free concentration, the plasma samples were prepared by ultrafiltration. A C18 column was used, with acetonitrile -0.01 mol·L-1 sodium dihydrogen phosphate (25∶75, pH adjusted to 3.3 by phosphoric acid) as the mobile phase, the detection wavelength was set at 240 nm, the column temperature was maintained at 35 ℃, and the flow rate was 1.0 mL·min-1. The specificity,linearity, the lower limit of quantitation, precession,recovery and stability of the developed method were validated. RESULTS The free concentration was linear with in 0.5-50 μg·mL-1, the lower limit of quantification was 0.5 μg·mL-1, and the method recovery rate was 94.63%-103.72%. The intra-day and inter-day precision(RSD) were all less than 4.00％; the linearity was good with in the total concentration of 1.562 5-100 μg·mL-1, the lower limit of quantification was 1.562 5 μg·mL-1, the method recovery rate was 94.55%-99.59%. The intra-day and inter-day precision(RSD) were all less than 4.00％. The TEIC was all stability at the conditions of maintaining at room temperature for 10 h,after freeze-thaw cycle and keeping at 4 ℃ for 72 h. CONCLUSION The method is simple, accurate, and sensitive, and is suitable for the clinical determination of total and free concentrations of teicoplanin and the study of pharmacokinetics.
关键词
高效液相色谱法 /
替考拉宁 /
血药浓度 /
游离浓度
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Key words
HPLC /
teicoplanin /
plasma concentration /
free concentration
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中图分类号：
R917
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参考文献
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脚注
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基金
龙岩市科技计划立项资助(2017LY66)
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