HPLC测定结直肠癌患者血浆中5-FU血药浓度及临床药代动力学研究

发布时间：2018-09-17 16:28

【摘要】：目的：建立一种简单、快速、灵敏的高效液相色谱法(HPLC)测定结肠癌患者血浆中5-氟尿嘧啶（5-FU）的浓度，并用于患者5-FU临床药代动力学研究。方法：1.采用醋酸铵缓冲液:异丙醇:乙酸乙酯混合液从血浆中萃取5-FU，建立和确证用于测定结肠癌患者血浆中5-FU浓度的HPLC方法。2.测定结肠癌患者血浆中5-FU浓度，并用药动学软件DAS2.0计算其药代动力学参数。3.测定结肠癌患者血浆中稳态5-FU浓度，并进行统计学分析。结果：1.HPLC系统及条件：色谱柱Inertsil ODS-SP C18(4.6mm×250mm)，预柱Phenomenex C18（4.0mm×3.0mm)；醋酸铵(PH=3.5):乙腈（97.5:2.5，v/v）为流动相进行等度洗脱，紫外检测波长265nm，柱温25℃，流速0.8ml/min,进样量为20μl。2.方法建立与确证：该方法专属性强，干扰峰少；血浆样品中5-FU在0.01-5μg/ml和5-100μg/ml范围内线性关系良好（R＞0.999）；最低检测限为10ng/ml；血浆样品日间和日内精密度RSD10%；相对回收率为85.24-104.14%；绝对回收率为87.55%-95.26%；5-FU在血浆中冻存和处理过程中基本稳定，保留时间为7分钟。3.结直肠癌患者的主要药代动力学参数：前5例患者，AUC，MRT，T1/2，V，CL和Cmax值范围分别为504.31-748.85mg/L*min，7.25-18.02min，5.41-23.56min，4.45-26.68L/m2，0.53-0.79L/min/m2，29.47-46.94mg/L。后5例患者，AUC，MRT，T1/2，V，CL和Cmax范围分别为12.28-75.17mg/L*min，21.23-33.02min，34.23-79.46min，383.81-3094.81L/m2，3.52-26.99L/min/m2，0.44-1.60mg/ml。4.结直肠癌患者血浆中5-FU稳态浓度为：前5例稳态药物浓度Css范围：2.655-56.995mg/L,另5例患者Css范围：0.019-1.324mg/L。前者稳态药物浓度显著高于后者（P0.05）。结论：1.本论文建立和确证的HPLC方法，专属性高、简便、快速、灵敏，成功用于结肠癌患者血浆中5-FU浓度的测定和临床药代动力学研究。2.5-FU静脉给药后，在结直肠癌患者药代动力学参数和稳态血药浓度个体差异大。为了提高疗效和降低毒性，我们应通过分析药代动力学行为，优化5-FU个体化给药来获得理想的5-FU稳态血药浓度，对指导临床合理用药具有重要意义。
[Abstract]:Objective: to establish a simple, rapid and sensitive high performance liquid chromatography (HPLC) method for the determination of 5-fluorouracil (5-FU) in plasma of patients with colon cancer and to study the pharmacokinetics of 5-FU. Method 1: 1. 5-FU was extracted from plasma with ammonium acetate buffer solution: isopropanol and ethyl acetate mixture. A HPLC method was established and confirmed for the determination of plasma 5-FU concentration in colon cancer patients. The plasma concentration of 5-FU was measured in colon cancer patients, and pharmacokinetic parameters were calculated by pharmacokinetic software DAS2.0. 3. The steady-state 5-FU levels in the plasma of colon cancer patients were measured and statistically analyzed. Results 1. HPLC system and conditions: Inertsil ODS-SP C18 (4.6mm 脳 250mm), Phenomenex C18 (4.0mm 脳 3.0mm), PH=3.5: acetonitrile (97.5: 2.5 v / v) as mobile phase, UV detection wavelength 265 nm, column temperature 25 鈩，

本文编号：2246482