Simultaneous Determination of Tegafur and Gimeracil in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry

被引:5
作者
Gu, Yuan [1 ,2 ]
Lu, Rong [1 ]
Si, Duanyun [2 ]
Liu, Changxiao [1 ]
机构
[1] Tianjin Inst Pharmaceut Res, Tianjin State Key Lab Pharmacokinet & Pharmacodyn, Tianjin 300193, Peoples R China
[2] Tianjin Univ, Sch Chem Engn & Technol, Tianjin 300072, Peoples R China
关键词
SOLID TUMORS; PHASE-I; METABOLIC-ACTIVATION; 5-FLUOROURACIL; S-1; PHARMACOKINETICS; FLUOROURACIL; FTORAFUR; R; S-1-(TETRAHYDRO-2-FURANYL)-5-FLUOROURACIL; 5-CHLORO-2,4-DIHYDROXYPYRIDINE;
D O I
10.2116/analsci.25.1211
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
We developed a rapid, simple and sensitive LC/MS/MS method for the simultaneous quantitation of tegafur (FT) and gimeracil (CDHP) in human plasma with a concentration range of 20 - 5000 and 2 - 500 ng/mL, respectively. Methanol was chosen as a precipitation agent for sample preparation. Chromatographic separation was performed on an inertsil ODS-3 C-18 column using 1.0% formic acid in water and methanol (80/20, v/v) at a flow rate of 0.3 mL/min. The MS detection was operated with selected reaction monitoring (SRM) in the positive-ion mode. The matrix effect ranged from -8.9 to 7.8% for all analytes. The intra- and inter-day precisions were less than 8.6 and 9.5%, and the accuracy was within +/- 7.5% for all analytes, respectively. The mean recoveries were 76.5 +/- 5.2 and 78.3 +/- 5.9% for FT and CDHP, respectively. The analytes were stable under all possible conditions of storing and handling for each compound.
引用
收藏
页码:1211 / 1215
页数:5
相关论文
共 20 条
[1]   A ROLE FOR DIHYDROPYRIMIDINE DEHYDROGENASE AND THYMIDYLATE SYNTHASE IN TUMOR SENSITIVITY TO FLUOROURACIL [J].
BECK, A ;
ETIENNE, MC ;
CHERADAME, S ;
FISCHEL, JL ;
FORMENTO, P ;
RENEE, N ;
MILANO, G .
EUROPEAN JOURNAL OF CANCER, 1994, 30A (10) :1517-1522
[2]   Sensitive liquid chromatographic assay for the simultaneous determination of 5-fluorouracil and its prodrug, tegafur, in beagle dog plasma [J].
Chu, DF ;
Gu, JK ;
Liu, WH ;
Fawcett, JP ;
Dong, QG .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2003, 795 (02) :377-382
[3]   Phase I and pharmacokinetic study of the oral fluoropyrimidine S-1 on a once-daily-for-28-day schedule in patients with advanced malignancies [J].
Chu, QSC ;
Hammond, LA ;
Schwartz, G ;
Ochoa, L ;
Rha, SY ;
Denis, L ;
Molpus, K ;
Roedig, B ;
Letrent, SP ;
Damle, B ;
DeCillis, AP ;
Rowinsky, EK .
CLINICAL CANCER RESEARCH, 2004, 10 (15) :4913-4921
[4]  
Cohen SJ, 2002, CLIN CANCER RES, V8, P2116
[5]  
ELSAYED YM, 1983, CANCER RES, V43, P4039
[6]   METABOLIC-ACTIVATION OF FTORAFUR [R,S-1-(TETRAHYDRO-2-FURANYL)-5-FLUOROURACIL] - THE MICROSOMAL OXIDATIVE PATHWAY [J].
ELSAYED, YM ;
SADEE, W .
BIOCHEMICAL PHARMACOLOGY, 1982, 31 (18) :3006-3008
[7]  
HEGGIE GD, 1987, CANCER RES, V47, P2203
[8]  
Hirata K, 1999, CLIN CANCER RES, V5, P2000
[9]   Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor agent in animal model and in patients with impaired renal function [J].
Ikeda, M ;
Furukawa, H ;
Imamura, H ;
Shimizu, J ;
Ishida, H ;
Masutani, S ;
Tatsuta, M ;
Kawasaki, T ;
Satomi, T .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2002, 50 (01) :25-32
[10]   High-performance liquid chromatographic determination of 5-fluorouracil and its prodrugs, tegafur and 4-deoxy-5-fluorouracil, in rat plasma [J].
Jarugula, VR ;
Boudinot, FD .
JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS, 1996, 677 (01) :199-203