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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(150mm×3.9mm,4μm);流动相:含0.1%三乙胺的乙腈-0.02mol·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1.0mL·min-1;检测波长273nm;柱温30℃。用该法测定10名慢性阻塞性肺疾病患者连续6d静脉滴注多索茶碱300mg.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0.05～8.0μg·mL-1(r=0.9999),血清最低检测浓度为0.01μg·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AUC0～t为(31.06±6.29)μg·h·mL-1,Vc为(26.53±11.77)L,T1/2α为(0.05±0.01)h,T1/2β为(1.72±0.44)h,CLs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。
OBJECTIVE: To establish a HPLC method for determination of doxofylline in plasma and to study the pharmacokinetics of doxofylline in patients with chronic obstructive pulmonary disease by intravenous drip. METHODS: A Waters C18 stainless steel column (150 mm × 3.9 mm, 4 μm) was used. The mobile phase consisted of 0.1% triethylamine in acetonitrile and 0.02 mol·L -1 sodium phosphate monobasic buffer (adjusted to pH 6.8 with sodium hydroxide ± 0.1) (15:85); flow rate 1.0mL · min-1; detection wavelength 273nm; column temperature 30 ℃. Using this method, 10 patients with chronic obstructive pulmonary disease were dosed intravenously with 300 mg doxofylline for 6 consecutive days, and the pharmacokinetic parameters were calculated by 3P97 software. Results: The linear range of plasma concentration was 0.05 ~ 8.0μg · mL-1 (r = 0.9999), the lowest serum concentration was 0.01μg · mL-1, the recovery rate was 103.2% ~ 105.0% n = 5) were 0.84% ~ 3.2% and 3.9% ~ 7.9% respectively. The pharmacokinetic parameters AUC0 ~ t (31.06 ± 6.29) μg · h · mL-1, Vc (26.53 ± 11.77) L, and T1 / 2α in 10 chronic obstructive pulmonary disease patients (0.05 ± 0.01) h, T1 / 2β was (1.72 ± 0.44) h, and CLs was (23.64 ± 5.02) L · h-1. Conclusion: The method is stable, reliable, easy to operate and has high sensitivity. It can be used for the determination of doxofylline in patients with chronic obstructive pulmonary disease and pharmacokinetic study.