HPLC测定慢性阻塞性肺疾病患者血清中多索茶碱浓度及其药动学研究___

摘要  目的：建立多索茶碱血药浓度的高效液相色谱检测法，并用于研究静脉滴注多索茶碱在慢性阻塞性肺疾病患者体内药动学行为。方法：采用Waters C₁₈不锈钢色谱柱(150 mm×3.9 mm,4 μm)；流动相：含0.1%三乙胺的乙腈-0.02 mol·L^-1磷酸二氢钠缓冲液(用氢氧化钠调pH至6.8±0.1)(15︰85)；流速1.0 mL·min^-1；检测波长273 nm；柱温30 ℃。用该法测定10名慢性阻塞性肺疾病患者连续6 d静脉滴注多索茶碱300 mg·次^-1，1次·d^-1血清药物浓度，应用3P97软件计算药动学参数。结果：血药浓度线性范围为0.05~8.0 μg·mL^-1(r＝0.9999)，血清最低检测浓度为0.01 μg·mL^-1，方法回收率为103.2%~105.0%，日内、日间RSD(n=5)分别为0.84%~3.2%和3.9%~7.9%。10名慢性阻塞性肺疾病患者静脉滴注多索茶碱的药动学参数AUC_0~t为(31.06±6.29) μg·h·mL^-1，V_c为(26.53±11.77) L，T_1/2α为(0.05±0.01) h，T_1/2β为(1.72±0.44) h，CL_s为(23.64±5.02) L·h^-1。结论：本法稳定、可靠，操作简单，灵敏度高，可用于临床慢性阻塞性肺疾病患者多索茶碱的血药浓度测定及药动学研究。

关键词: 高效液相色谱法；多索茶碱；血药浓度；慢性阻塞性肺疾病(COPD)；药代动力学

 

 

Abstract  Objective:To establish an HPLC method for determination of doxophylline in serum and study its pharmacokinetics in chronic obstructive pulmonary disease(COPD) patients after intravenous administration.Methods:The doxophylline in serum was determinated by HPLC at 273 nm.The sample was separated on Waters C₁₈(150 mm×3.9 mm,4 μm),eluted with acetonitrile consists of 0.1% triethylamine-0.02 mol·L^-1 NaH₂PO₄ buffer(pH was adjusted to 6.8±0.1 with NaOH) (15∶85) as the mobile phase at flow rate 1.0 mL·min^-1.The column temperature was 30 ℃.The HPLC method was used to determinated the doxophylline in COPD patients after intravenous administration(300 mg, once-daily) from days 1 to 6. The pharmacokinetic parameters were analyzed by 3P97. Results:It showed a good linear range of 0.05-8.0 μg·mL^-1(r＝0.9999).The limited detection concentration was 0.01 μg·mL^-1.The method recovery was 103.2%-105.0%, the intra-day RSD and the inter-day RSD were 0.84%-3.2% and 3.9%-7.9%(n=5).After intravenous administration of doxophylline in 10 COPD patients,the main pharmacokinetic parameters AUC_0-t,V_c,T_1/2α,T_1/2β and CL_s were (31.06±6.29) μg·h·mL^-1,(26.53±11.77) L,(0.05±0.01) h,(1.72±0.44) h and (23.64±5.02) L·h^-1 respectively.Conclusion:This method is stable,convenient and sensitive.It is suitable for determination of concentration of doxophylline in clinic and requirement of pharmacokinetic study.

Key words:HPLC;doxophylline;serum drug concentration;chronic obstructive pulmonary disease(COPD);pharmacokinetics