人血清中氟尿苷的HPLC测定方法

摘　要：目的　建立人血清中氟尿苷的HPLC测定方法。方法　取血清200μL，以甲硝唑为内标，采用正丙醇/叔丁基甲醚作为提取液进行两次提取。常温氮气下吹干，流动相复溶后进样分析。色谱柱：Shim-PackCLC-ODS柱；流动相：乙腈-磷酸缓冲液-水(75∶100∶900)；流速：0.6mL^.min^-1；检测波长：268nm。结果　在0.005～0.5mg^.L^-1的范围内线性良好，相关系数r=0.9999(n=8)。低、中、高3个浓度质控样品的批内RSD在1.97%～4.09%之间，批间RSD在3.19%～3.96%之间，方法学回收率为100.88%～107.00%，富集进样时0.001mg^.L^-1的氟尿苷血清标准品可被检出。结论　本方法灵敏度高，操作简便易行，为研究其临床药物动力学、PK/PD关系等提供了方法学基础。

关键词：氟尿苷；高效液相色谱法；血清

分类号：R917；R927.2⁺　文献标识码：A
文章编号：1001-2494(2001)02-0118-03

High-performance liquid chromatographic determination of floxuridine in human serum

WANG Peng（Department of Pharmacy,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China）　
ZHU Zhu（Department of Pharmacy,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China）　
FU Qiang（Department of Pharmacy,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China）　
YE Min（Department of Pharmacy,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China）　
LI Da-kui（Department of Pharmacy,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China）　

Abstract：OBJECTIVE　To develop an HPLC method for the determination of floxuridine in human serum.METHODS　With metronidazole as the internal standard,200 μL of serum was extracted by n-propyl alcohol/methyl t-butyl ether in a two-step extraction.The organic layer was evaporated under nitrogen stream and the residual was reconstituted with the mobile plase.A Shim-Pack CLC-ODS column was selected and the mobile phase was consisted of acetonitrile-phosphate buffer-water (75∶100∶900) at a flow rate of 0.6 mL^.min^-1.The detection wavelength was 268 nm.RESULTS　A linearitywas obtained from 0.005 to 0.5 mg^.L^-1 of floxuridine in serum with a good correlation coefficient (r=0.9999,n=8).The intra-run and inter-run coefficients of variation were less than 4.09%.The mean recoveries were 103.00%,107.00% and 100.88% for the low,middle and high concentrations of check samples,respectively.The limit of detection was 0.001 mg^.L^-1.CONCLUSION　The method was sensitive,specific and simple.It is suitable for clinical pharmacokinetic study.

Keywords：floxuridine;HPLC;serum

参考文献：

［1］Zhu Z,Fu Q,Nightingale H CH,et al.Pharmacokinetics of 5-fluorouracil and its penetration into pancreatic juice in dogs[J].Acta Pharmacologica Sinica,1998,19(1):7.
［2］孟旭，陈兰英，徐小薇.静脉滴注5-氟尿嘧啶用于滋养细胞肿瘤化疗的药物代谢动力学研究[J].中国临床药理学杂志，1988，4(3)：135.
［3］Muggia Frank M,Chan Kenneth K,Russell Christy,et al.Phase Ⅰ and pharmacologic evaluation of intraperitoneal 5-Fluoro-2?-deoxyuridine[J].Cancer Chemother Pharmacol,1991,28:241.
［4］Michaelis Hans Christoph,Foth Heidi,Kahl Georo Friedrich.Determination of 5-Fluoro-2?-deoxyuridine in human plasma by high-performance liquid chromatography with pre-column fluorimetric derivatization[J].J Chromatography,1987,416:176.
［5］Barberi-Heyob M,Merlin JL,Weber B.Determination of 5-Fluorouracil and its main metabolites in plasma by high-performance liquid chromatography[J].J Chromatography,1992,573:247.
［6］Joulia JM,Pinguet F,Grosse PY,et al.Determination of 5-Fluorouracil and its main metabolies in plasma by high-performance liquid chromatography:Application to a pharmacokinetic study[J].J Chromatography B,1997,692:427.
［7］Jung M,Berger G,Pohlen U,et al.Simultaneous determination of 5-Fluorouracil and its active metabolites in serum and tissue by high-performance liquid chromatography[J].J Chromatography B,1997,702:193.
［8］LaCreta Frank P.High-performance liquid chromatographic analysis of fluoropyrimidine nucleosids and fluorouracil in plasma[J].J Chromatography,1987,414:197.

收稿日期：2000年2月28日

出版日期：2001年2月8日