Odagiri H, Ichihara S, Semura E, Utoh M, Tateishi M, Kuruma I
Department of Drug Metabolism and Product Development, Nippon Roche Research Center, Kanagawa, Japan.
J Pharmacobiodyn. 1988 Apr;11(4):234-40. doi: 10.1248/bpb1978.11.234.
A method for determination of 5-fluorouracil (5-FU) has been established for pharmacokinetic study of 5'-deoxy-5-fluorouridine (5'-DFUR), a newly developed prodrug of 5-FU. 5-FU was extracted with diethyl-ether containing 1-propanol and methylated with CH3I in the presence of (CH3)4NOH. The methylated 5-FU was analyzed by gas chromatography-mass spectrometry using 15N2-5-FU as an internal standard. Quantitation was carried out by selected-ion monitoring of molecular ions of N,N-dimethyl-5-FU (m/z 158) and the internal standard (m/z 160). The sensitivity (greater than 2 ng/g sample), specificity and precision of the method were satisfactory for application to clinical studies of this drug. After an oral administration of 5'-DFUR (800 mg/body) to patients with cancer, 5-FU in plasma peaked within 1 h and eliminated with an apparent half life of about 1 h.
已建立一种测定5-氟尿嘧啶（5-FU）的方法，用于对新开发的5-FU前药5'-脱氧-5-氟尿苷（5'-DFUR）进行药代动力学研究。5-FU用含1-丙醇的乙醚萃取，并在（CH3）4NOH存在下用CH3I进行甲基化。甲基化的5-FU以15N2-5-FU作为内标，通过气相色谱-质谱联用仪进行分析。通过对N，N-二甲基-5-FU（m/z 158）和内标（m/z 160）的分子离子进行选择离子监测来进行定量。该方法的灵敏度（大于2 ng/g样品）、特异性和精密度对于该药物的临床研究应用而言令人满意。对癌症患者口服5'-DFUR（800 mg/体）后，血浆中的5-FU在1小时内达到峰值，并以约1小时的表观半衰期消除。
