AI Article Synopsis
- A systematic metabolite profiling approach is essential for detecting and characterizing drug metabolites, and this study focuses on flibanserin (FLB), the first of its kind to explore its metabolic fate.
- Advanced techniques like in silico analysis and high-resolution mass spectrometry were used to identify and elucidate 14 new metabolites from FLB through in vitro and in vivo studies involving liver microsomes and biological samples from rats.
- The research also examined metabolic pathways and potential toxicity of the metabolites, confirming findings using software tools like Pro Tox-II.
Article Abstract
A systematic metabolite profiling approach has paramount importance in detecting, identifying, and characterizing drug metabolites. Till date, there is no report published on the comprehensive metabolic fate of flibanserin (FLB). In this study, the structure of entire potential metabolites of FLB has been elucidated by execution of in silico tool and high resolution mass spectrometry based metabolite profiling strategy employing data-dependent and data-independent approaches. In vitro metabolism profile was investigated after incubating FLB with liver microsomes (rat and human) and S9 fractions in presence of their respective co-factors. In vivo metabolites were identified from rat plasma, urine, feces, and brain tissue samples. An efficient extraction technique was developed that made it possible to identify the metabolites generated even in extremely low concentrations. Extraction was carried out by precipitating protein and thereafter solid-phase extraction to enrich their concentration in the sample before analysis. Fourteen new metabolites have been identified and characterized. Most of the metabolites of FLB were generated due to hydrolysis and oxidation followed by glucuronide, sulfate, and methyl conjugation. Additionally, a spiking study was employed to confirm the presence of N-oxide metabolite in human liver S9 fraction and rat urine samples. Moreover, we have established the probable biotransformation pathway of FLB and successfully analyzed the toxicity potential of the metabolites using Pro Tox-II software.
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| http://dx.doi.org/10.1016/j.jchromb.2021.123011 | DOI Listing |
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