Measurement of plasma uracil using gas chromatography-mass spectrometry in normal individuals and in patients receiving inhibitors of dihydropyrimidine dehydrogenase

被引:25
作者
Bi, DQ
Anderson, LW
Shapiro, J
Shapiro, A
Grem, JL
Takimoto, CH
机构
[1] NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci,Natl Naval Med Ctr, Bethesda, MD 20889 USA
[2] US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Rockville, MD 20850 USA
来源
JOURNAL OF CHROMATOGRAPHY B | 2000年 / 738卷 / 02期
关键词
uracil; eniluracil; dihydropyrimidine dehydrogenase;
D O I
10.1016/S0378-4347(99)00528-9
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A sensitive gas chromatographic-mass spectrometric method is described for reliably measuring endogenous uracil in 100 mu l of human plasma. Validation of this assay over a wide concentration range, 0.025 mu M to 250 mu M (0.0028 mu g/ml to 28 mu g/ml), allowed for the determination of plasma uracil in patients treated with agents such as eniluracil, an inhibitor of the pyrimidine catabolic enzyme, dihydropyrimidine dehydrogenase. Calibration standards were prepared in human plasma using the stable isotope, [N-15(2)]uracil, to avoid interference from endogenous uracil and 10 mu M 5-chlorouracil was added as the internal standard. Published by Elsevier Science B.V.
引用
收藏
页码:249 / 258
页数:10
相关论文
共 25 条
  • [1] Simultaneous gas chromatographic mass spectrophotometric determination of alpha-fluoro-beta-alanine and 5-flaorouracil in plasma
    Anderson, D
    Kerr, DJ
    Blesing, C
    Seymour, LW
    [J]. JOURNAL OF CHROMATOGRAPHY B, 1997, 688 (01): : 87 - 93
  • [2] GAS-CHROMATOGRAPHIC MASS-SPECTROMETRIC METHOD FOR ROUTINE MONITORING OF 5-FLUOROURACIL IN PLASMA OF PATIENTS RECEIVING LOW-LEVEL PROTRACTED INFUSIONS
    ANDERSON, LW
    PARKER, RJ
    COLLINS, JM
    AHLGREN, JD
    WILKINSON, D
    STRONG, JM
    [J]. JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1992, 581 (02): : 195 - 201
  • [3] 5-ETHYNYLURACIL (776C85) - A POTENT MODULATOR OF THE PHARMACOKINETICS AND ANTITUMOR EFFICACY OF 5-FLUOROURACIL
    BACCANARI, DP
    DAVIS, ST
    KNICK, VC
    SPECTOR, T
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (23) : 11064 - 11068
  • [4] Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase
    Baker, SD
    Khor, SP
    Adjei, AA
    Doucette, M
    Spector, T
    Donehower, RC
    Grochow, LB
    Sartorius, SE
    Noe, DA
    Hohneker, JA
    Rowinsky, EK
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (12) : 3085 - 3096
  • [5] ELEVATED URINE, BLOOD AND CEREBROSPINAL-FLUID LEVELS OF URACIL AND THYMINE IN A CHILD WITH DIHYDROTHYMINE DEHYDROGENASE-DEFICIENCY
    BAKKEREN, JAJM
    DEABREU, RA
    SENGERS, RCA
    GABREELS, FJM
    MAAS, JM
    RENIER, WO
    [J]. CLINICA CHIMICA ACTA, 1984, 140 (03) : 247 - 256
  • [6] BERGLUND G, 1979, CLIN CHEM, V25, P1325
  • [7] CAO S, 1995, CANCER RES, V55, P6227
  • [8] Chazal M, 1996, CLIN CANCER RES, V2, P507
  • [9] Sorivudine and 5-fluorouracil; a clinically significant drug-drug interaction due to inhibition of dihydropyrimidine dehydrogenase
    Diasio, RB
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1998, 46 (01) : 1 - 4
  • [10] Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer:: A potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage
    Gamelin, E
    Boissdron-Celle, M
    Guérin-Meyer, V
    Delva, R
    Lortholary, A
    Genevieve, F
    Larra, F
    Ifrah, N
    Robert, J
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (04) : 1105 - 1110