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目的:建立同时测定大鼠血浆中阿霉素和塞来昔布的液相色谱-串联质谱(LC/MS/MS)方法,研究这两种药物联合应用的药代动力学。方法:大鼠尾静脉注射阿霉素和塞来昔布,眼眶取血并抗凝,离心分离血浆,采用乙酸乙酯提取血浆中的阿霉素和塞来昔布,N2吹干乙酸乙酯,残留物用50μL甲醇溶解,取20μL用于LC/MS/MS分析。结果:用LC/MS/MS法检测大鼠血浆中阿霉素和塞来昔布的线性范围为1-800ng/mL,日内、日间精密度(RSD)均小于15%,检测血浆低、中、高三个浓度(8、50、500ng/mL)阿霉素的回收率分别为101.2%、95.1%和91.4%,检测血浆低、中、高三个浓度(8、50、500ng/mL)塞来昔布的回收率分别为105.6%、106.8%和93.7%。大鼠尾静脉注射5.8mg/kg阿霉素和3.8mg/kg塞来昔布的半衰期分别为2.3h和3.6h,曲线下面积分别为670ng·h·mL-1和1480ng·h·mL-1。结论:建立的方法灵敏、准确、快速,适用于阿霉素和塞来昔布的药代动力学研究。
OBJECTIVE: To establish a liquid chromatography-tandem mass spectrometry (LC / MS / MS) method for the simultaneous determination of doxorubicin and celecoxib in rat plasma and to study the pharmacokinetics of these two drugs in combination. METHODS: Adriamycin and celecoxib were injected into the caudal vein of rats, blood was taken from the orbital and anticoagulated, the plasma was separated by centrifugation, the doxorubicin and celecoxib in plasma were extracted with ethyl acetate, and then ethyl acetate The residue was dissolved in 50 μL of methanol and 20 μL was taken for LC / MS / MS analysis. Results: The linear range of doxorubicin and celecoxib in rat plasma was 1-800 ng / mL by LC / MS / MS. The intra- and inter-day precision was less than 15%, and the plasma low, The recoveries of middle and high concentrations of doxorubicin (8,50,500 ng / mL) were 101.2%, 95.1% and 91.4%, respectively. The plasma concentrations of low, middle and high concentrations of 8,50,500 ng / mL The recovery of celecoxib was 105.6%, 106.8% and 93.7% respectively. The half-lives of rat tail vein injection of 5.8 mg / kg doxorubicin and 3.8 mg / kg of celecoxib were 2.3 h and 3.6 h, respectively, and the areas under the curve were 670 ng · h-mL-1 and 1480 ng · h-mL- 1. Conclusion: The established method is sensitive, accurate and rapid and suitable for pharmacokinetic studies of doxorubicin and celecoxib.