Determination of 5-fluorouracil and its prodrug tegafur by derivatization and gas chromatography

• Main Authors: Cheng-Wei Lin, 林政葦
• Other Authors: Hwang-Shang Kou
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/67751975029258167749

碩士 === 高雄醫學大學 === 藥學研究所碩士班 === 93 === Analytical derivatization coupled with gas chromatography-electron capture detection (GC-ECD), a simple and sensitive method has been developed for the quantitative analysis of 5-fluorouracil (5-FU) and its prodrug tegafur (TF; Ftorafur), an chemotherapeutic antineoplastic agent, in human plasma. TF and 5-FU were derivatized with 2-(pentafluorophenoxy)ethyl 2-(piperidino)ethanesulfonate (PFPES) in a acetonitrile, using potassium carbonate and 18-crown-6 ether as reaction activators. The resulting derivatives of TF and 5-FU were analyzed by capillary gas chromatography with an electron-capture detector (GC-ECD). 2,2’-dinitrobiphenyl was used as an internal standard (I.S.), and the peak area ratios of TF and 5-FU derivatives to I.S. were used for quantitative analysis. The detection limit (signal to noise ratio = 3, injected volume 1 �尳) of TF and 5-FU was about 1 �嵱 and 0.1 �嵱. Several parameters affecting the derivatization of TF and 5-FU such as the concentration of derivatizating agent, the concentration of 18-crown-6 ether, the amount of base, the reaction temperature and reaction time were discussed. Application of the method to the analysis of TF and 5-FU in human plasma was studied. TF and 5-FU were extracted with acetonitrile and ethyl acetate (40:60, v/v) from 200 �尳 plasma. The linear range for the quantitation of TF and 5-FU in spiked plasma was 5-250 �嵱 �v1~50 μg/mL) and 0.5-125 �嵱�v0.065~16.25 μg/mL) with a correlation coefficient of 0.995. The relative recovery for TF and 5-FU in plasma was greater than 98.07 %. The method can be used for analysis of TF and 5-FU in human plasma.