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Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
Identification of novel ondansetron metabolites using LC/MSn and NMR
Mingyu Duan1, Li Qin2, Dafang Zhong3
1School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China; Bioanalysis Center, Quarkman Pharmaceutical Technology Co., LTD, A1 Innovation Park, New and High-Tech Development Zone, Benxi, Liaoning 117020, China.
Abstract:
Ondansetron, a potent and highly sensitive 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, has been used for the treatment of chemotherapy- and radiotherapy-induced nausea and vomiting. The isolation and identification of ondansetron metabolites were investigated in our research. The feces and bile samples collected after oral administration of ondansetron were extracted and then isolated by semi-preparative HPLC. Then the pretreated samples were characterized by LC/MSn and NMR. In rats feces, a total of four metabolites were isolated and elucidated including 7-hydroxyl-ondansetron (M1), 8-hydroxyl-ondansetron (M2), 7-hydroxyl-N-desmethyl-ondansetron (M3), and 8-hydroxyl-N-desmethyl-ondansetron (M4). In addition, a kind of metabolite of phase II isolated in rats bile was characterized as N-desmethyl-ondansetron-7-O-β-D-glucuronide (M5). To our knowledge, three metabolites were reported for the first time. LC/MSn and NMR-based approach was proved to be useful for full structure elucidation of unknown metabolites. The systematic metabolites isolation and elucidation provided metabolite reference standards for metabolites detection of ondansetron.
Insights
Researchers identified five new ondansetron metabolites in rat feces and bile, including three previously unreported compounds. This study provides crucial metabolite standards for detecting ondansetron in biological samples.
Area of Science:
- Pharmacology and Toxicology
- Drug Metabolism and Pharmacokinetics
Background:
- Ondansetron is a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist used to manage chemotherapy- and radiotherapy-induced nausea and vomiting.
- Understanding ondansetron's metabolic pathways is crucial for optimizing its therapeutic use and assessing potential drug interactions.
Purpose of the Study:
- To isolate and identify the metabolites of ondansetron in rat biological samples (feces and bile).
- To characterize novel ondansetron metabolites using advanced analytical techniques.
- To establish metabolite reference standards for future detection and quantification studies.
Main Methods:
- Oral administration of ondansetron to rats, followed by collection of feces and bile samples.
- Extraction and isolation of metabolites using semi-preparative High-Performance Liquid Chromatography (HPLC).
- Structural elucidation of isolated metabolites employing Liquid Chromatography-Mass Spectrometry (LC/MSn) and Nuclear Magnetic Resonance (NMR) spectroscopy.
Main Results:
- Four phase I metabolites were identified in rat feces: 7-hydroxyl-ondansetron (M1), 8-hydroxyl-ondansetron (M2), 7-hydroxyl-N-desmethyl-ondansetron (M3), and 8-hydroxyl-N-desmethyl-ondansetron (M4).
- One phase II metabolite, N-desmethyl-ondansetron-7-O-β-D-glucuronide (M5), was identified in rat bile.
- Three of the identified metabolites (M1, M2, M3, M4, M5) represent novel findings, reported for the first time.
Conclusions:
- The study successfully isolated and elucidated five ondansetron metabolites in rats, expanding the known metabolic profile of the drug.
- The combined LC/MSn and NMR approach proved effective for comprehensive structural characterization of unknown drug metabolites.
- The generated metabolite standards are valuable for future research, enabling accurate detection and quantification of ondansetron metabolites in biological matrices.
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