Department of Chemistry, Forman Christian College, Lahore 54600, Pakistan.
Department of Pharmacology, University of Health Sciences, Khayaban-e-Jamia Punjab, Lahore 54600, Pakistan.
Molecules. 2024 Sep 6;29(17):4226. doi: 10.3390/molecules29174226.
This study aimed at the biotransformation of sumatriptan by , , and subsp. and the identification of the drug metabolites by liquid chromatography-mass spectrometry. The drug was incubated with the organisms in tryptic soya broth at 37 °C. The broth was filtered and subjected to liquid chromatography-mass spectrometry. The metabolites identified by the use of mass spectral (+ve ion mode) fragmentation patterns were (3-methylphenyl)methanethiol (), 1-(4-amino-3-ethylphenyl)-N-methylmethanesulfonamide ( subsp. ) and 1-{4-amino-3-[(1E)-3-(dimethylamino)prop-1-en-1-yl]phenyl}methanesulfinamide (, , , ). These metabolites exhibit high gastrointestinal absorption, no blood-brain barrier permeability (except (3-methylphenyl)methanethiol), a bioavailability score of 0.55 and no inhibitory effect on CYP2C19, CYP2C9, CYP2D6, CYP3A4 or cytochrome P450 1A2 (except (3-methylphenyl)methanethiol), as determined by SwissADME software ver. 2024. The metabolites appear to be more toxic than the parent drug, as suggested by their calculated median lethal dose values. All four organisms under investigation transformed sumatriptan to different chemical substances that were more toxic than the parent drug.
本研究旨在通过 和 亚种转化舒马曲坦，并通过液相色谱-质谱法鉴定药物代谢物。将药物与生物体在胰蛋白酶大豆肉汤中于 37°C 孵育。将肉汤过滤并进行液相色谱-质谱分析。通过使用质谱（+ 离子模式）碎片模式鉴定的代谢物为（3-甲基苯基）甲硫醇（）、1-（4-氨基-3-乙基苯基）-N-甲基甲磺酰胺（）和 1-{4-氨基-3-[(1E)-3-（二甲基氨基）丙-1-烯-1-基]苯基}甲磺酰胺（、、、）。这些代谢物表现出高胃肠道吸收、无血脑屏障通透性（除（3-甲基苯基）甲硫醇外）、生物利用度评分为 0.55 且对 CYP2C19、CYP2C9、CYP2D6、CYP3A4 或细胞色素 P450 1A2 无抑制作用（除（3-甲基苯基）甲硫醇外），这是由 SwissADME 软件 ver.2024 确定的。代谢物似乎比母体药物更具毒性，这从它们的计算中位致死剂量值可以看出。所有四种被研究的生物体都将舒马曲坦转化为比母体药物毒性更大的不同化学物质。
