Rapid structure identification of nineteen metabolites of ondansetron in human urine using LC/MSn
Mingyu Duan1,2, Li Qin1, Dafang Zhong3
1Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China.
Abstract:
Ondansetron, a 5-hydroxytryptamine type 3 (5-HT3 ) receptor antagonist, is regarded as an excellent candidate to treat chemotherapy- and radiotherapy-induced nausea and vomiting. To better understand the metabolic profiles of ondansetron in human urine, the metabolites were analyzed using liquid chromatography/mass spectrometry (LC/MSn ). Urine samples were collected after oral administration of 8 mg ondansetron to healthy volunteers. Then samples were treated by solid-phase extraction and detected with LC/MSn . Besides ondansetron, in human urine, a total of 19 metabolites including 13 new metabolites were detected and identified via comparing the retention time and product ion spectra with those of reference standards isolated and characterized. The results showed that ondansetron was metabolized via hydroxylation, glucuronidation, sulfation and minor N-demethylation in human. LC/MSn was demonstrated to be useful and sensitive in the metabolic study of ondansetron.
Insights
Ondansetron, a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, is metabolized in humans via hydroxylation, glucuronidation, sulfation, and N-demethylation. Liquid chromatography/mass spectrometry identified 19 metabolites in urine, including 13 new ones.
Area of Science:
- Pharmacology and Toxicology
- Analytical Chemistry
- Metabolomics
Background:
- Ondansetron is a key antiemetic for managing nausea and vomiting induced by chemotherapy and radiotherapy.
- Understanding ondansetron's metabolic pathways in humans is crucial for optimizing its therapeutic use and safety profile.
Purpose of the Study:
- To comprehensively analyze the metabolic profile of ondansetron in human urine.
- To identify and characterize novel metabolites of ondansetron.
- To evaluate the utility of liquid chromatography/tandem mass spectrometry (LC/MSn) in ondansetron metabolic studies.
Main Methods:
- Urine samples were collected from healthy volunteers following oral administration of 8 mg ondansetron.
- Solid-phase extraction was employed for sample preparation.
- Liquid chromatography/tandem mass spectrometry (LC/MSn) was used for metabolite detection and identification.
Main Results:
- Ondansetron and a total of 19 metabolites were detected in human urine.
- Thirteen novel metabolites of ondansetron were identified.
- Metabolism occurred primarily through hydroxylation, glucuronidation, and sulfation, with minor N-demethylation.
Conclusions:
- Ondansetron undergoes extensive metabolism in humans, primarily via Phase II conjugation pathways.
- LC/MSn is a sensitive and effective technique for the detailed metabolic profiling of ondansetron.
- The identification of new metabolites provides a more complete understanding of ondansetron's pharmacokinetic and pharmacodynamic properties.
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