目的 建立HPLC法测定人血浆中亚胺培南浓度,并基于稳定性试验结果建立临床标本采样流程。方法 以0.01 mol·L^-1乙酸铵缓冲液(pH 6.8)-乙腈(95∶5,V∶V)为流动相,用Agilent Zorbax SB-AQ(4.6 mm×250 mm,5 μm)色谱柱,进样量30 μL,柱温30 ℃,流速1.0 mL·L^-1,紫外检测波长298 nm,分别考察了在不同温度,加入稳定剂等条件下亚胺培南的稳定性。结果 亚胺培南在3.30～105.60 μg·mL^-1线性关系良好(R²=0.999 1),定量下限为0.41 μg·mL^-1,批内回收率在97.83%～103.54%,批间回收率在99.43%～104.24%,日内、日间RSD＜15.0%;在稳定性血浆中,亚胺培南在低温、室温条件下可分别稳定72 h和18 h,在非稳定性血浆中,分别为24 h和6 h。结论 本方法简便、快速、准确,可用于监测亚胺培南浓度,且基于稳定性试验建立临床标本采样流程,能确保血药浓度监测结果准确性。

Objective To determine the concentration of imipenem in human plasma by HPLC method, and establish the sampling process of clinical specimens based on stability investigation result. Methods The mobile phase was consisted of 0.01 mol·L^-1 ammonium acetate buffer(pH 6.8)-acetonitrile(95∶5, V∶V), and using Agilent Zorbax SB-AQ column(4.6 mm×250 mm,5 μm)to investigat the stability of imipenem under different temperature and with or without stabilizer. The injection volume was 30 μL, the colum temperature was 30℃, the flow rate was 1.0 mL·L^-1 and the detection wavelength was 298 nm. Results Imipenem had a good correlation coefficient(R²=0.999 1)at concentration of 3.30-105.60 μg·mL^-1. The lower limit of quantification was 0.41 μg·mL^-1, the intra-batch and inter-batch recovery rate were 97.83%-103.54% and 99.43%-104.24%, the intra-day and inter-day RSD were less than 15.0%. In stabilized plasma, imipenem could maintain stable at low temperature for 72 h and room temperature for 18 h, in non-stabilized plasma for 24 h and 6 h respectively. Conclusions This method was simple, rapid and accurate, which was suitable for the imipenem therapeutic drug monitoring, and establishing the sampling process of clinical specimen based on stability test could ensure the accuracy of plasma concentration monitoring.