Dataset Information

Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF.

ABSTRACT: Determination of the metabolism pathway of xenobiotics undergoing the hepatic pass is a crucial aspect in drug development since the presence of toxic biotransformation products may result in significant side effects during the therapy. In this study, the complete hepatic metabolism pathway of dapoxetine established according to the human liver microsome assay with the use of a high-resolution LC-MS system was described. Eleven biotransformation products of dapoxetine, including eight metabolites not reported in the literature so far, were detected and identified. N-dealkylation, hydroxylation, N-oxidation and dearylation were found to be the main metabolic reactions for the investigated xenobiotic. In silico analysis of toxicity revealed that the reaction of didesmethylation may contribute to the increased carcinogenic potential of dapoxetine metabolites. On the other hand, N-oxidation and aromatic hydroxylation biotransformation reactions possibly lead to the formation of mutagenic compounds.

SUBMITTER: Skibinski R

PROVIDER: S-EPMC8270242 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF.

Skibiński Robert R Trawiński Jakub J Gawlik Maciej M

Molecules (Basel, Switzerland) 20210622 13

Determination of the metabolism pathway of xenobiotics undergoing the hepatic pass is a crucial aspect in drug development since the presence of toxic biotransformation products may result in significant side effects during the therapy. In this study, the complete hepatic metabolism pathway of dapoxetine established according to the human liver microsome assay with the use of a high-resolution LC-MS system was described. Eleven biotransformation products of dapoxetine, including eight metabolite ...[more]

PMID: 34206424

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Project description:Traditional Chinese medicines (TCM)/herbal medicines (HM) are too complicated to comprehensively investigate their quality consistency effectively with a single detection technique. Hence, finding an effective, rapid, and comprehensive quality control (QC) method is of great importance for guaranteeing the safety and efficacy of TCM/HM in clinical applications. In our current research, a novel strategy of multi-wavelength fusion HPLC fingerprints and ultraviolet (UV) spectroscopic fingerprinting was proposed and successfully applied to monitor the quality consistency of compound liquorice tablets (CLT). The quality grades of 35 CLT samples from two manufacturers were successfully discriminated and evaluated by the averaged linear quantified fingerprint method (ALQFM) from a qualitative and quantitative perspective. The results showed that the UV spectroscopic fingerprints agreed well with the multi-wavelength fusion HPLC fingerprints. In addition, ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-Q-TOF-MS) was applied to investigate the chemical constituents in CLT samples, providing an important chemical structural foundation for further QC and bioactivity studies. Additionally, a simple flow injection analysis (FIA) was developed to investigate the antioxidant capacity in CLT, which was based on the scavenging of 2,2-diphenyl-1-picrylhydrazyl radicals by antioxidants. Furthermore, the fingerprint-efficacy relationship between high-performance liquid chromatography (HPLC) fingerprints and the antioxidant activities of CLT samples was established utilizing orthogonal projection to latent structures (OPLS). In conclusion, this study indicated that integrating UHPLC-ESI-Q-TOF-MS/MS, UV spectroscopic fingerprints, and multi-wavelength fusion HPLC fingerprints coupled with the antioxidant activities reported could give important clues for further pharmacological and clinical studies of CLT. Meanwhile, it provides a practical strategy for the rapid screening and identifying of TCM/HM quality consistency.

Dataset Information

Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF.

Publications

Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF.

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