unspecific monooxygenase | 9038-14-6

• 分子结构分类: 氧化还原酶 - 作用于配对供体，掺入或还原分子氧 - 以还原型黄素或黄素蛋白作为一个供体，另一个供体含一个氧原子
• 英文名称: unspecific monooxygenase
• 英文别名: microsomal monooxygenase；xenobiotic monooxygenase；aryl-4-monooxygenase；aryl hydrocarbon hydroxylase；microsomal P-450；flavoprotein-linked monooxygenase；flavoprotein monooxygenase；substrate,reduced-flavoprotein:oxygen oxidoreductase (RH-hydroxylating or -epoxidizing)；recombinant human CYP₂D₆
• CAS: 9038-14-6；62213-32-5

反应信息

• 作为试剂：
  描述：

  他莫昔芬 在 D-葡萄糖-6-磷酸 、 unspecific monooxygenase 、 nicotinamide adenine dinucleotide phosphate 、 magnesium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 生成 4-羟基三苯氧胺
  参考文献：
  名称：

  Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method development for screening of potential tamoxifen-drug/herb interaction via in vitro cytochrome P450 inhibition assay

  摘要：

  Screening for potential drug-drug interaction (DDI) or herb-drug interaction (HDI) using in vitro cytochrome P450 inhibition (IVCI) assays requires robust analytical methods with high sensitivity and reproducibility. Utilization of liquid chromatography-mass spectrometry (LC-MS) for analyte quantification is often hampered by the presence of non-volatile IVCI sample buffer constituents that often results in ion suppression. In this study, to enable screening of drug interactions involving tamoxifen (TAM) metabolism using IVCI-LC-MS/MS, a liquid-liquid extraction (LLE) method was developed and optimized for sample clean-up. Utilization of chloroform as extraction solvent and adjustment of sample pH to 11 was found to result in satisfactory recovery ( > 70%) and low ion suppression ( < 19%). A LC-MS/MS method was subsequently developed and validated for simultaneous quantification of major TAM metabolites, such as N-desmethyltamoxifen (NDT), endoxifen (EDF) and 4-hydroxytamoxifen (HTF) to enable IVCI sample analysis. Satisfactory separation of E-/Z-isomers of endoxifen with peak resolution (Rs) of 1.9 was achieved. Accuracy and precision of the method was verified within the linear range of 0-50 ng/mL for NDT, 0-25 ng/mL for HTF and 0-25 ng/mL for EDF (E/Z isomers). Inhibitory potency (IC50, K-i and mode of inhibition) of known CYP inhibitors and Strobilanthes crispus extract was then evaluated using the validated method. In summary, the results demonstrated applicability of the developed LLE and validated LC-MS/MS method for in vitro screening of DDI and HDI involving TAM metabolism.

  DOI：

  10.1016/j.jchromb.2020.122148