米卡芬净对厄他培南血浆蛋白结合率的影响

Effect of Micafungin on Plasma Protein Binding Rate of Ertapenem

关键词:  厄他培南  米卡芬净  高效液相色谱法  游离药物浓度  蛋白结合率

Key words:  ertapenem  micafungin  HPLC  free drug concentration  plasma protein binding rate

摘要:

目的 建立HPLC测定人血浆中游离厄他培南浓度的方法，并研究米卡芬净对厄他培南血浆蛋白结合率的影响。方法 用超滤法进行样品处理，色谱柱为DiamonsiL C₁₈（4.6 mm×150 mm，5.0 μm），流动相为乙腈-10 mmol·-L¹ 醋酸钠溶液（12.4∶87.6），流速为1.0 mL·min^-1，检测波长为295 nm，柱温为35℃，进样量10 μL。采用超滤法结合HPLC，测定未加和加入米卡芬净后厄他培南的人血浆蛋白结合率。结果 游离厄他培南浓度在2～50 μg·mL^-1内线性关系良好（r=0.999）；低中高浓度厄他培南回收率分别为（102.3±2.5）%，（97.6±3.1）%和（98.6±2.2）%；日内、日间精密度均<5%。与米卡芬净合用后，厄他培南血浆蛋白结合率无显著变化。结论 该法可测定厄他培南游离浓度，方法准确快捷，灵敏度高。在人血浆中米卡芬净不影响厄他培南的体外蛋白结合率。

Abstract:

OBJECTIVE To establish a method for determining the concentration of free ertapenem in human plasma by HPLC. And to study the effect of micafungin on the plasma protein binding rate of ertapenem. METHODS Sample processed by ultrafiltration. A Diamonsil C₁₈ (4.6 mm×150 mm, 5.0 μm) column was used, with the mobile phase of acetonitrile-10 mmol·L^-1 sodium acetate solution (12.4:87.6) at the flow rate of 1 mL·min^-1, the detection wavelength was 295 nm, column temperature was 35℃ and injection volume was 10 μL. Ultrafiltration was combined with HPLC to determine the plasma protein binding rate of ertapenem after undosing and adding micafungin. RESULTS The method was validated over the concentration range of 2-50 μg·mL^-1 for ertapenem in human plasma, and there was excellent linearity (r=0.999). The recovery rates of low, middle, high dose of ertapenem were (102.3±12.5)%, (97.6±3.1)% and (98.6±2.2)%; the intra-day and inter-day RSD were both <5%. The protein binding rate of ertapenem was no significant change in association with micafungin. CONCLUSION The method for determinating concentration of free ertapenem in plasma is rapid, accurate and sensitive. Micafungin has no effect on the in vitro protein binding rate of ertapenem in human plasma.