Determination of tamoxifen and metabolites in serum by capillary electrophoresis using a nonaqueous buffer system

被引:37
作者
Sanders, JM
Burka, LT
Shelby, MD
Newbold, RR
Cunningham, ML
机构
来源
JOURNAL OF CHROMATOGRAPHY B | 1997年 / 695卷 / 01期
关键词
tamoxifen; N-desmethyltamoxifen; 4-hydroxytamoxifen;
D O I
10.1016/S0378-4347(97)00099-6
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Tamoxifen (TAM), an antiestrogen, is widely used to treat hormone-dependent breast cancer in post-menopausal women. TAM may be used as a chemopreventive agent in women of child-bearing age; however, few data exist describing potential TAM-induced fetal toxicity. In support of the National Toxicology Program's characterization of reproductive and developmental effects of TAM, this work describes an analytical technique utilizing capillary electrophoresis (CE) for the detection of circulating levels of TAM, N-desmethyltamoxifen (DMT), and 4-hydroxytamoxifen (4-HT) in maternal rodent serum. Greater than 90% of H-3-labeled TAM was extractable from serum using 98:2 hexane-isoamyl alcohol. Optimum separation of TAM, DMT, and 4-HT was obtained on a 57 cmX50 mu m capillary using a nonaqueous buffer system of 1:1 methanol-acetonitrile containing 50 mM ammonium acetate and 1% acetic acid. 4-Dimethylaminopyridine was used as internal standard. Temperature and voltage were optimized at 40 degrees C and 15 kV, respectively. The limit of detection of TAM by UV detection at 214 nm was approximately 800 amol. TAM and DMT were confirmed in serum of female rats 4 h following a single oral dose of 120 mg/kg. Transplacental exposure of TAM to fetal tissue will be evaluated using this technique.
引用
收藏
页码:181 / 185
页数:5
相关论文
共 14 条
  • [1] BENSON LM, 1993, J HIGH RES CHROMATOG, V16, P324
  • [2] PEROXIDASE ACTIVATION OF TAMOXIFEN AND TOREMIFENE RESULTING IN DNA-DAMAGE AND COVALENTLY BOUND PROTEIN ADDUCTS
    DAVIES, AM
    MARTIN, EA
    JONES, RM
    LIM, CK
    SMITH, LL
    WHITE, INH
    [J]. CARCINOGENESIS, 1995, 16 (03) : 539 - 545
  • [3] HORMONAL CHEMOPREVENTION OF CANCER IN WOMEN
    HENDERSON, BE
    ROSS, RK
    PIKE, MC
    [J]. SCIENCE, 1993, 259 (5095) : 633 - 638
  • [4] JORDAN VC, 1995, P SOC EXP BIOL MED, V208, P144
  • [5] TAMOXIFEN AND THE INDUCTION OF CANCER
    KING, CM
    [J]. CARCINOGENESIS, 1995, 16 (07) : 1449 - 1454
  • [6] HORMONAL THERAPY OF BREAST-CANCER - NEW APPROACHES AND CONCEPTS
    LEGHA, SS
    DAVIS, HL
    MUGGIA, FM
    [J]. ANNALS OF INTERNAL MEDICINE, 1978, 88 (01) : 69 - 77
  • [7] A COMPARATIVE-STUDY OF TAMOXIFEN METABOLISM IN FEMALE RAT, MOUSE AND HUMAN LIVER-MICROSOMES
    LIM, CK
    YUAN, ZX
    LAMB, JH
    WHITE, INH
    DEMATTEIS, F
    SMITH, LL
    [J]. CARCINOGENESIS, 1994, 15 (04) : 589 - 593
  • [8] HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY OF TAMOXIFEN AND METABOLITES IN PLASMA AND TISSUES
    LIM, CK
    CHOW, LCL
    YUAN, ZX
    SMITH, LL
    [J]. BIOMEDICAL CHROMATOGRAPHY, 1993, 7 (06) : 311 - 314
  • [9] Moorthy B, 1996, CANCER RES, V56, P53
  • [10] SEPARATION OF TAMOXIFEN AND METABOLITES BY CAPILLARY ELECTROPHORESIS WITH NONAQUEOUS BUFFER SYSTEM
    NG, CL
    LEE, HK
    LI, SFY
    [J]. JOURNAL OF LIQUID CHROMATOGRAPHY, 1994, 17 (18): : 3847 - 3857