HPLC法同时测定乳腺癌患者血浆中多柔比星、表柔比星及环磷酰胺的血药浓度  

Simultaneous determination on plasma concentrations of doxorubicin,epirubicin and cyclophosphamide in breast cancer patients by HPLC

作　　者：权会丽[1] 曹佳丽 程丽娟 文迪 史贺 QUAN Hui-li;CAO Jia-li;CHENG Li-juan;WEN Di;SHI He(The Fourth Hospital of Shijiazhuang,Shijiazhuang 050011,China)

机构地区：[1]石家庄市第四医院,石家庄050011

出　　处：《药物分析杂志》2020年第7期1236-1242,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立一种同时测定多柔比星、表柔比星及环磷酰胺血药浓度的方法并考察其在乳腺癌患者血浆中的浓度差异。方法:采用双波长高效液相色谱法,色谱柱为Waters XBridge C18(150 mm×4.6 mm,3.5μm),流动相为甲醇-0.01 mol·L^-1磷酸二氢铵溶液-冰醋酸,梯度洗脱,流速1.0 mL·min^-1,检测波长254nm(多柔比星、表柔比星)、190 nm(环磷酰胺)。选取27例多柔比星、表柔比星联合环磷酰胺治疗方案的乳腺癌患者,检测其血药浓度。结果:多柔比星、表柔比星及环磷酰胺保留时间分别为8.86、9.89及13.95min,血药浓度分别在0.5~50 ng·mL^-1、0.5~50 ng·mL^-1及0.1~100μg·mL^-1范围内呈线性且关系良好,方法回收率均在85.0%以上;日内、日间RSD均<15%,不同剂量多柔比星/表柔比星与同剂量环磷酰胺联合使用,结果发现多柔比星高剂量给药方案组对患者环磷酰胺血药浓度有升高作用,但无统计学差异,表柔比星无此作用。结论:本研究建立了同时检测人血浆中多柔比星、表柔比星及环磷酰胺的方法,并且该方法适用于临床样本的测定,且通过不同剂量多柔比星、表柔比星与环磷酰胺联用,结果发现多柔比星对环磷酰胺血药浓度具有升高作用,但仍需进一步扩大样本量及开展作用机制研究。Objective:To establish a method for the simultaneous determination on plasma concentrations of doxorubicin,epirubicin and cyclophosphamide in patients with breast cancer.Methods:Dual-wavelength high performance liquid chromatography was used.The column was Waters XBridge C18(150 mm×4.6 mm,3.5 μm)and the mobile phase was methanol-0.01 mol·L^-1 ammonium dihydrogen phosphate solution-glacial acetic acid with gradient elution at the flow rate of 1.0 mL·min^-1.The determination of doxorubicin and epirubicin was under the wavelength of 254 nm while the detection wavelength of cyclophosphamide was 190 nm.Samples from 27 breast cancer patients treated with doxorubicin,epirubicin,and cyclophosphamide were included to determine the plasma drug concentrations.Results:The retention time of doxorubicin,epirubicin and cyclophosphamide was 8.86,9.89 and 13.95 min,respectively.Good linear relationships of plasma drug concentrations were showed in the ranges of 0.5-50 ng·mL^-1,0.5-50 ng·mL^-1 and 0.1^-100 μg·mL^-1.The recovery rates of the method were all above 85.0%,and the RSDs were less than 15% in intra-day and inter-day.Different doses of doxorubicin/epirubicin were used in combination with the same dose of cyclophosphamide,as results the plasma concentrations of cyclophosphamide in patients of doxorubicin high-dose regime group were increased but without statistical difference,and epirubicin showed no such effect.Conclusion:In this study,a method for simultaneous determination of doxorubicin,epirubicin and cyclophosphamide in human plasma is established,and this method is suitable for the determination of clinical samples.By the combination of different doses of doxorubicin,epirubicin and cyclophosphamide,it is found that doxorubicin might has an effect on increasing the plasma concentration of cyclophosphamide,while further investigation with expanded sample size on the mechanism of action are required.

关 键 词：多柔比星 表柔比星 环磷酰胺 血药浓度 乳腺癌 高效液相色谱 双波长检测 

分 类 号：R917[医药卫生—药物分析学]