Abstract

To date, many analogies of sildenafil, tadarafil, and vadenafil, which are phosphodiesterase-5 (PDE5) inhibitor have been reported. On the other hand, a novel type of PDE5 inhibitor, thioquinapiperifil has not yet been evaluated. Therefore, in this study, liquid chromatography quadrupole time of flight mass spectrometry (LC-Q-TOF-MS) was conducted to determine the in vitro and in vivo metabolites of thioquinapiperifil. Metabolites in urine and feces samples of rats injected with thioquinapiperifil and in human liver microsomal extract were characterized to examine its possible metabolic pathways. Metabolized samples were extracted and precipitated using acetonitrile and subsequently injected into the LC-Q-TOF-MS system. Peaks of interest were analyzed via tandem-mass spectrometry to identify the metabolite structure. A total of 11, 5, and 7 metabolites were detected in human liver microsomal extract, rat urine, and rat feces, respectively. The mass error values of all TOF mass results were within 5 ppm, indicating high accuracy. These newly identified metabolites may be useful for evaluating the toxicology of thioquinapiperifil and this knowledge may be applied to related forensic cases.

摘要

迄今为止，已经报道了作为磷酸二酯酶 5 (PDE5) 抑制剂的西地那非、他达拉非和伐地那非的许多类似物。另一方面，一种新型的 PDE5 抑制剂硫喹哌培非尚未得到评估。因此，本研究采用液相色谱四极杆飞行时间质谱 (LC-Q-TOF-MS) 测定体外和体内硫喹哌利非的代谢物。对注射硫喹哌利非的大鼠的尿液和粪便样本和人肝微粒体提取物中的代谢物进行表征，以检查其可能的代谢途径。使用乙腈提取和沉淀代谢样品，随后注入 LC-Q-TOF-MS 系统。通过串联质谱分析感兴趣的峰以确定代谢物结构。在人肝微粒体提取物、大鼠尿液和大鼠粪便中分别检测到 11、5 和 7 种代谢物。所有 TOF 质量结果的质量误差值均在 5 ppm 以内，表明准确度很高。这些新发现的代谢物可能有助于评估硫喹哌培非的毒理学，这些知识可应用于相关的法医案件。