HPLC测定猪血浆和胰腺组织中的5-FU及其在胰腺癌区灌注化疗效果评价中的应用

DETERMINATION OF FLOURACIL IN PIG PLASMA AND PANCREATIC TISSUE BY HPLC

目的 采用HPLC测定猪血浆及其胰腺组织中 5 -氟尿嘧啶 (5 -FU)的浓度 ,研究猪不同部位给予 5 -FU后血浆及组织中的浓度差异。方法 以C1 8-A柱为固定相 ,水 (pH 2 .0 ) -甲醇 (95∶5)为流动相 ,2 66nm检测。用建立的方法测定了 1 4只健康幼猪分别自十二指肠动脉、脾动脉及左耳缘静脉途径滴注 5 -FU后血浆及胰腺组织中 5 -FU的浓度 ,以配对t检验比较不同部位给药后血浆及胰腺组织中 5 -FU的浓度差异。结果 所建立的方法浓度在 0 .5～ 2 0 μg·ml- 1 范围内线性关系良好 (r =0 .9993) ,平均血浆回收率为 99.2 % ,RSD =5 .5 % ;平均组织回收率为 96 .2 % ,RSD =4.5 %。测得经十二指肠动脉或脾动脉途径滴注 5 -FU与经左耳缘静脉全身化疗相比极大地增高了胰腺组织内的 5 -FU浓度 ,显著降低灌注期间周围循环血中的药物浓度。结论 该方法简便、杂质干扰少 ,结果准确。 5

OBJECTIVE To establish an HPLC method to determine 5-FU in pig plasma and pancreatic tissue, and to investigate the concentration of 5-FU in jugular vein,portal vein and pancreatic tissue.METHODS The flourouracil concentrations in pig plasma and pancreatic tissue after solvent extraction were determined by HPLC with a C 18 -A column. The mobile phase was composed by water (pH 2.0)-methanol (95∶5) and the detection wavelength was 266 nm.14 pigs were randomly divided into 3 groups to determine 5-FU concentrations in plasma and pancreatic tissue in pigs after 5-FU was perfused into gastroduodenal artery, splenic artery and left periotic vein,respectively.RESULTS The regression line was linear within the concentration range of 0.5～20 mg·ml -1 ( r = 0.9993 ); the plasma recovery was 99.2%, RSD = 5.5% ;The tissue recovery was 96.2%, RSD =5.5%.Compared with systemic chemotherapy, regional perfusion to pancreas with 5-FU after gastroduodenal artery or splenic artery ligation significantly increased the concentration of 5-FU in pancreatic tissue and decreased the peripheral drug concentration.CONCLUSION The analysis method can be used in the determination of 5 FU concentration in plasma and tissue.