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目的采用HPLC法同时测定慢性阻塞性肺病(COPD)患者血浆中的茶碱及其代谢物1,3-二甲基尿酸(1,3-DMU)。方法色谱柱为Hypersil BDS C18柱(250 mm×4.6 mm,5μm),流动相为乙腈-水(7∶93),流速1 m L·min-1,检测波长280 nm。43名COPD患者连续服用茶碱(100 mg,bid)两周后,测定茶碱及1,3-DMU的血药浓度。结果茶碱、1,3-DMU的线性范围分别为0.20~10.00μg·m L-1(r=0.9998)、0.05~2.00μg·m L-1(r=0.9996);日内、日间RSD均≤12.91%,提取回收率分别为77.52%~79.22%、71.69%~74.02%;患者的平均茶碱血药浓度为3.57±1.59μg·m L-1,茶碱和1,3-DMU的浓度呈强相关(r=0.672),1,3-DMU/茶碱为0.064±0.024。结论所用方法简便、快速、准确,可用于COPD患者茶碱血药浓度的监测,1,3-DMU与茶碱浓度的比值可评估不同个体对茶碱清除率的差异。
Objective To determine the theophylline and its metabolite 1,3-dimethylurea (1,3-DMU) in plasma of patients with chronic obstructive pulmonary disease (COPD) by HPLC. Methods The column was Hypersil BDS C18 (250 mm × 4.6 mm, 5 μm). The mobile phase consisted of acetonitrile-water (7:93) and the flow rate was 1 m L · min-1. The detection wavelength was 280 nm. Forty-three patients with COPD received a continuous dose of theophylline (100 mg bid) for two weeks and then measured the plasma concentrations of theophylline and 1,3-DMU. Results The linear range of theophylline and 1,3-DMU was 0.20-10.00 μg · mL -1 (r = 0.9998) and 0.05-2.00 μg · mL -1 (r = 0.9996) respectively. The intra-day and inter-day RSD ≤12.91% .The recovery rates were from 77.52% to 79.22% and from 71.69% to 74.02% respectively. The average theophylline concentration was 3.57 ± 1.59μg · m L-1, and theophylline and 1,3-DMU concentrations There was a strong correlation (r = 0.672) and 1,3-DMU / theophylline was 0.064 ± 0.024. Conclusions The method is simple, rapid and accurate and can be used to monitor the plasma concentration of theophylline in COPD patients. The ratio of theophylline clearance rate between different individuals can be evaluated by the ratio of 1,3-DMU to theophylline concentration.