A fast method for the analysis of ethosuximide and detection of proteins in huh-7 cell after cotreatment with ethosuximide and other drugs by mass spectrometry
| Autor: | Ying-Jung Wu, 吳盈蓉 |
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| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 Ethosuximide (3-ethyl-3-methylpyrrolidine-2,5-dione) is an antiepileptic drug with first select in the treatment of absence seizure. The mechanism by which ethosuximide blocks T-type calcium channels to prevent accepting calcium in thalamic neurons and gain the effect of anticonvulsant. Most of the patients keep taking ethosuximide to prevent seizure. When seizure duration, patients must monitor therapeutic drug of plasma concentration for regulating dose and gain the therapeutic concentration and reduce clinical hepatotoxicity. Previous studies have confirmed that ethosuximide has teratogenic effect, so it is important to develop a method for therapeutic drug monitoring of anticonvulsants for pregnancy. This study establishes a quick method for ethosuximide analysis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). This method also could be applied for the purpose of quality control in pharmaceutical factory. Additionally, patients who take ethosuximide long time to prevent the activity of seizure may also take other drugs in clinical treatment, such as cimetidine (inhibition of gastric acid), ketotifen (antihistamine), metformin (control blood sugar) and metronidazole (antibiotic). This study discusses the effects of ethosuximide co-treatment with these drugs by huh-7 cell line and profiling their protein expressions by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and bioinformatics to predict hepatotoxicity and other side effects. The fast method has been established and is applicable for ethosuximide monitoring in human plasma and quality control of pharmaceutical formulation. The results show that good precision and accuracy are obtained the relative standard deviation (RSD) and relative error (RE) were < 13%. In protein analysis, co-treatment with ethosuximide and cimetidine may produce liver cancer, liver fibrosis, hepatocellular carcinoma, nephritis predicted by bioinformatics. Thus, most of the attention in safety and toxicity was necessary. Furthermore, we find some repeated proteins that are associated with cancer and carcinoma and disorders of their normal physiological responses. Ultimately, drug-drug interaction studies and assessment of hepatotoxicity could provide useful information to help to prevent hepatotoxicity and avoid harmful side effects. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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