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Identification of metabolic pathways involved in the biotransformation of eslicarbazepine acetate using UPLC-MS/MS, human microsomal enzymes and in silico studies
Journal of King Saud University-Science ( IF 3.7 ) Pub Date : 2020-12-18 , DOI: 10.1016/j.jksus.2020.101281
Asif Husain , Farah Iram , Anees A. Siddiqui , Saeedah Musaed Almutairi , Osama B Mohammed , Shah Alam Khan , Syed Najmul Hejaz Azmi , Nafisur Rahman

In the last few decades, metabolite identification and detection have become an integral component of drug discovery process. The detection and depiction of an identified metabolite is significant for the development of safe and effective therapeutic agents as these metabolites may be pharmacologically active or toxic in nature. A (UPLC-MS/MS) method was developed for the quantification of eslicarbazepine acetate metabolite (M3), cis-10,11-dihydro-5H-dibenz[b,f]azepine-10,11-diol, in rat plasma. Eslicarbazepine acetate was extracted from rat plasma by precipitation technique using acetonitrile as a precipitating solvent. Chromatographic separation was accomplished using acetonitrile-0.01 M potassium dihydrogen phosphate (60:40, v/v) as mobile phase at a flow rate of 0.2 ml/min on Waters Acquity BEH 150 × 2.1 mm, 1.7 µm, C18 column at 30˚ C. The linearity of the calibration curve was 5–100 ng/ml for metabolite M3. The overall intra- and inter-day precision did not exceed 3%. In silico, in vitro and in vivo approaches have been used to facilitate the detection and depiction of eslicarbazepine acetate metabolites. MetabolExpert was used to predict the probable metabolites of the compounds. Metabolite of eslicarbazepine acetate was identified using human liver microsomes.



中文翻译:

涉及艾司利卡西平的生物转化代谢途径的鉴定乙酸盐使用UPLC-MS / MS,人类微粒体酶和在计算机芯片上的研究

在过去的几十年中,代谢物的鉴定和检测已成为药物发现过程不可或缺的组成部分。鉴定出的代谢物的检测和描绘对于开发安全有效的治疗剂具有重要意义,因为这些代谢物在本质上可能具有药理活性或毒性。建立了一种(UPLC-MS / MS)方法来定量测定埃司卡西平乙酸代谢物(M3)顺式-10,11-dihydro-5 H-dibenz [b,f] azepine-10,11-diol,在大鼠血浆中。以乙腈为沉淀溶剂,通过沉淀技术从大鼠血浆中提取乙酸依卡西平。使用乙腈-0.01 M磷酸二氢钾(60:40,v / v)作为流动相,以0.2 ml / min的流速在Waters Acquity BEH 150×2.1 mm,1.7 µm,C18色谱柱上于30°C进行色谱分离C.代谢物M3的校准曲线线性为5–100 ng / ml。日内和日间的整体精度不超过3%。在计算机上体外体内已经使用多种方法来促进对埃斯卡西平乙酸酯代谢物的检测和描绘。MetabolExpert用于预测化合物的可能代谢产物。使用人肝微粒体鉴定了醋酸依西卡西平的代谢物。

更新日期:2020-12-29
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