Flibanserin (FLB) is the first FDA approved drug showed to have significant activity against sexual desire disorder of premenopausal and postmenopausal women. Unfortunately, FLB is used as an adulterant in dietary supplement products as a performance enhancer in sports. Identification of FLB and its metabolites in the biological samples requires an authenticated analytical technique. The aim of this study was to identify N-oxide metabolite of FLB in microsomal and S9 human liver enzyme fractions, rat urine and feces. There are several N-oxide reported as genotoxic impurity or reactive metabolites based on position of N-oxide in piperazine ring. This study also describes the strategy to utilize degradation chemistry for isolation of N-oxide and its step-wise characterization. An LC-MS method has been developed and employed for identifying the N-oxide metabolite of FLB. The targeted N-oxide metabolite in the extracted ion chromatogram of the in vitro and in vivo samples has been confirmed by analyzing the changes in observed mass at m/z 407.1693. Major distinguished abundant ions at m/z 243.1104, 190.0974, 161.0705, 119.0601 confirmed the structure of the metabolite. This study will help to understand the oxidative potential of FLB in toxicokinetic study. The developed method can be useful to identify FLB or its N-oxide metabolite in dope testing in future. This is the first time to report a strategy to utilize degradation chemistry for N-oxide metabolite characterization. In this study, isolated N-oxidative degradation product was used to confirm N-oxide metabolite which was characterized by LC-MS through H/D exchange and structure was ensured by NMR spectroscopy (1H, COSY).

中文翻译：

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使用UHPLC-Q-TOF-MS / MS，H / D交换和NMR技术将大鼠尿液和粪便中的应激降解和代谢物谱合并以表征氟班色林的氧化​​代谢产物。

Flibanserin（FLB）是首个获得FDA批准的药物，对绝经前和绝经后妇女的性欲障碍具有显着活性。不幸的是，FLB在膳食补充剂产品中用作掺假品，作为运动中的性能增强剂。鉴定生物样品中的FLB及其代谢物需要经过验证的分析技术。这项研究的目的是鉴定微粒体和S9人肝酶组分，大鼠尿液和粪便中FLB的N氧化物代谢产物。根据哌嗪环中N氧化物的位置，有几种N氧化物被报告为遗传毒性杂质或反应性代谢物。这项研究还描述了利用降解化学分离N-氧化物及其逐步表征的策略。已经开发出一种LC-MS方法，并将其用于鉴定FLB的N-氧化物代谢物。通过分析m / z 407.1693处观察到的质量变化，可以确定体外和体内样品的提取离子色谱图中的目标N-氧化物代谢物。m / z 243.1104、190.0974、161.0705、119.0601处的主要显着丰富离子证实了该代谢物的结构。这项研究将有助于了解毒代动力学研究中FLB的氧化潜力。将来开发的方法可用于在涂料测试中鉴定FLB或其N氧化物代谢产物。这是首次报告将降解化学用于N-氧化物代谢产物表征的策略。在这个研究中，