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利用气液色谱法和高效液相色谱法对人及实验动物中美芬妥因的羟基化和去甲基化代谢物进行分析。

Analysis of hydroxylated and demethylated metabolites of mephenytoin in man and laboratory animals using gas-liquid chromatography and high-performance liquid chromatography.

作者信息

Küpfer A, James R, Carr K, Branch R

出版信息

J Chromatogr. 1982 Oct 8;232(1):93-100. doi: 10.1016/s0378-4347(00)86011-9.

DOI:10.1016/s0378-4347(00)86011-9
PMID:7142342
Abstract

Separation of urinary mephenytoin metabolites was evaluated under various gas-liquid chromatographic (GLC) and high-performance liquid chromatographic (HPLC) conditions. A simple and rapid alkylation procedure is described for GLC-using a nitrogen sensitive thermionic detector. The in situ formation of sodium methinylsulfinylmethide is used as base for the perpropylation of hydantoins and their metabolites. Normal-and reversed-phase HPLC of the underivatized compounds was performed using four different types of stationary phases. None of the GLC systems separated all the six hydantoin compounds tested, whereas, normal-and reversed-phase HPLC were able to obtain a complete separation of these compounds. The major metabolites of mephenytoin were 5-phenyl-5-ethylhydantoin, 3-methyl-5-(4-hydroxyphenyl)-5-ethylhydantoin and 5-(4-hydroxyphenyl)-5-ethylhydantoin in man, rat, mouse, rabbit, and guinea pig. 3-Methyl-5-phenyl-5-(2-hydroxyethyl)-hydantoin and 3-methyl-5-(3-hydroxyphenyl)-5-ethylhydantoin are major metabolites in the dog.

摘要

在各种气液色谱(GLC)和高效液相色谱(HPLC)条件下,对尿中美芬妥因代谢物的分离进行了评估。描述了一种简单快速的烷基化方法,用于使用氮敏感热离子检测器的GLC分析。次甲基亚磺酰甲基钠的原位形成被用作乙内酰脲及其代谢物丙基化的碱。使用四种不同类型的固定相,对未衍生化的化合物进行了正相和反相HPLC分析。所有测试的GLC系统均未分离出所有六种乙内酰脲化合物,而正相和反相HPLC能够完全分离这些化合物。在人、大鼠、小鼠、兔和豚鼠中,美芬妥因的主要代谢物为5-苯基-5-乙基乙内酰脲、3-甲基-5-(4-羟基苯基)-5-乙基乙内酰脲和5-(4-羟基苯基)-5-乙基乙内酰脲。3-甲基-5-苯基-5-(2-羟乙基)-乙内酰脲和3-甲基-5-(3-羟基苯基)-5-乙基乙内酰脲是犬体内的主要代谢物。

相似文献

1
Analysis of hydroxylated and demethylated metabolites of mephenytoin in man and laboratory animals using gas-liquid chromatography and high-performance liquid chromatography.利用气液色谱法和高效液相色谱法对人及实验动物中美芬妥因的羟基化和去甲基化代谢物进行分析。
J Chromatogr. 1982 Oct 8;232(1):93-100. doi: 10.1016/s0378-4347(00)86011-9.
2
Assay of mephenytoin metabolism in human liver microsomes by high-performance liquid chromatography.
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3
Stereoselectivity of the arene epoxide pathway of mephenytoin hydroxylation in man.
Epilepsia. 1984 Feb;25(1):1-7. doi: 10.1111/j.1528-1157.1984.tb04148.x.
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A major pathway of mephenytoin metabolism in man. Aromatic hydroxylation to p-hydroxymephenytoin.
Drug Metab Dispos. 1980 Jan-Feb;8(1):1-4.
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Mephenytoin hydroxylation deficiency: kinetics after repeated doses.美芬妥因羟化缺乏症:重复给药后的动力学
Clin Pharmacol Ther. 1984 Jan;35(1):33-9. doi: 10.1038/clpt.1984.5.
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Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man.美芬妥英的药物遗传学:人类一种新的药物羟基化多态性
Eur J Clin Pharmacol. 1984;26(6):753-9. doi: 10.1007/BF00541938.
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Stereochemical aspects of the metabolism of 5-ethyl-5-phenylhydantoin (Nirvanol) in the dog.
Drug Metab Dispos. 1981 Sep-Oct;9(5):393-401.
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Stereoselectivity of differential routes of drug metabolism: the fate of the enantiomers of [14C]mephenytoin in the dog.
J Pharmacol Exp Ther. 1979 May;209(2):190-5.
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Characterization of mephenytoin metabolites in human urine by gas chromatography and mass spectrometry.
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Stereoselective mephobarbital hydroxylation cosegregates with mephenytoin hydroxylation.立体选择性美索比妥羟基化与美芬妥因羟基化共分离。
Clin Pharmacol Ther. 1985 Oct;38(4):414-8. doi: 10.1038/clpt.1985.196.

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