【摘要】：目的：建立一種簡單、快速、靈敏的高效液相色譜法(HPLC)測定結(jié)腸癌患者血漿中5-氟尿嘧啶（5-FU）的濃度，并用于患者5-FU臨床藥代動力學(xué)研究。方法：1.采用醋酸銨緩沖液:異丙醇:乙酸乙酯混合液從血漿中萃取5-FU，建立和確證用于測定結(jié)腸癌患者血漿中5-FU濃度的HPLC方法。2.測定結(jié)腸癌患者血漿中5-FU濃度，并用藥動學(xué)軟件DAS2.0計算其藥代動力學(xué)參數(shù)。3.測定結(jié)腸癌患者血漿中穩(wěn)態(tài)5-FU濃度，并進行統(tǒng)計學(xué)分析。結(jié)果：1.HPLC系統(tǒng)及條件：色譜柱Inertsil ODS-SP C18(4.6mm×250mm)，預(yù)柱Phenomenex C18（4.0mm×3.0mm)；醋酸銨(PH=3.5):乙腈（97.5:2.5，v/v）為流動相進行等度洗脫，紫外檢測波長265nm，柱溫25℃，流速0.8ml/min,進樣量為20μl。2.方法建立與確證：該方法專屬性強，干擾峰少；血漿樣品中5-FU在0.01-5μg/ml和5-100μg/ml范圍內(nèi)線性關(guān)系良好（R＞0.999）；最低檢測限為10ng/ml；血漿樣品日間和日內(nèi)精密度RSD10%；相對回收率為85.24-104.14%；絕對回收率為87.55%-95.26%；5-FU在血漿中凍存和處理過程中基本穩(wěn)定，保留時間為7分鐘。3.結(jié)直腸癌患者的主要藥代動力學(xué)參數(shù)：前5例患者，AUC，MRT，T1/2，V，CL和Cmax值范圍分別為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范圍分別為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.結(jié)直腸癌患者血漿中5-FU穩(wěn)態(tài)濃度為：前5例穩(wěn)態(tài)藥物濃度Css范圍：2.655-56.995mg/L,另5例患者Css范圍：0.019-1.324mg/L。前者穩(wěn)態(tài)藥物濃度顯著高于后者（P0.05）。結(jié)論：1.本論文建立和確證的HPLC方法，專屬性高、簡便、快速、靈敏，成功用于結(jié)腸癌患者血漿中5-FU濃度的測定和臨床藥代動力學(xué)研究。2.5-FU靜脈給藥后，在結(jié)直腸癌患者藥代動力學(xué)參數(shù)和穩(wěn)態(tài)血藥濃度個體差異大。為了提高療效和降低毒性，我們應(yīng)通過分析藥代動力學(xué)行為，優(yōu)化5-FU個體化給藥來獲得理想的5-FU穩(wěn)態(tài)血藥濃度，對指導(dǎo)臨床合理用藥具有重要意義。
[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，

本文編號：2246482