Dose-response technique combined with stable isotope tracing for drug metabolite profiling by using high-resolution mass spectrometry
Background: Mass spectrometry metabolomics-based data-processing approaches have been developed for drug metabolite profiling. However, existing approaches cannot be used to comprehensively identify drug metabolites with high efficacy.Methods: Herein, we propose a two-stage data-processing approach...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1293540/full |
| _version_ | 1797392947333824512 |
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| author | I-Shou Lin Chia-Ying Anderin Chuang Chia-Lung Shih |
| author_facet | I-Shou Lin Chia-Ying Anderin Chuang Chia-Lung Shih |
| author_sort | I-Shou Lin |
| collection | DOAJ |
| description | Background: Mass spectrometry metabolomics-based data-processing approaches have been developed for drug metabolite profiling. However, existing approaches cannot be used to comprehensively identify drug metabolites with high efficacy.Methods: Herein, we propose a two-stage data-processing approach for effective and comprehensive drug metabolite identification. The approach combines dose-response experiments with stable isotope tracing (SIT). Rosiglitazone (ROS), commonly used to treat type 2 diabetes, was employed as a model drug.Results: In the first stage of data processing, 1,071 features exhibited a dose-response relationship among 22,597 features investigated. In the second stage, these 1,071 features were screened for isotope pairs, and 200 features with isotope pairs were identified. In time-course experiments, a large proportion of the identified features (69.5%: 137 out of 200 features) were confirmed to be possible ROS metabolites. We compared the validated features identified using our approach with those identified using a previously reported approach [the mass defect filter (MDF) combined with SIT] and discovered that most of the validated features (37 out of 42) identified using the MDF-SIT combination were also successfully identified using our approach. Of the 143 validated features identified by both approaches, 74 had a proposed structure of an ROS-structure-related metabolite; the other 34 features that contained a specific fragment of ROS metabolites were considered possible ROS metabolites. Interestingly, numerous ROS-structure-related metabolites were identified in this study, most of which were novel.Conclusion: The results reveal that the proposed approach can effectively and comprehensively identify ROS metabolites. |
| first_indexed | 2024-03-08T23:56:02Z |
| format | Article |
| id | doaj.art-aaa478af3107461395100d666f80ea4b |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T23:56:02Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-aaa478af3107461395100d666f80ea4b2023-12-13T05:19:31ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-12-011410.3389/fphar.2023.12935401293540Dose-response technique combined with stable isotope tracing for drug metabolite profiling by using high-resolution mass spectrometryI-Shou Lin0Chia-Ying Anderin Chuang1Chia-Lung Shih2Department of Anesthesiology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi City, TaiwanResearch Center for Environmental Changes, Academia Sinica, Taipei, TaiwanClinical Research Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi City, TaiwanBackground: Mass spectrometry metabolomics-based data-processing approaches have been developed for drug metabolite profiling. However, existing approaches cannot be used to comprehensively identify drug metabolites with high efficacy.Methods: Herein, we propose a two-stage data-processing approach for effective and comprehensive drug metabolite identification. The approach combines dose-response experiments with stable isotope tracing (SIT). Rosiglitazone (ROS), commonly used to treat type 2 diabetes, was employed as a model drug.Results: In the first stage of data processing, 1,071 features exhibited a dose-response relationship among 22,597 features investigated. In the second stage, these 1,071 features were screened for isotope pairs, and 200 features with isotope pairs were identified. In time-course experiments, a large proportion of the identified features (69.5%: 137 out of 200 features) were confirmed to be possible ROS metabolites. We compared the validated features identified using our approach with those identified using a previously reported approach [the mass defect filter (MDF) combined with SIT] and discovered that most of the validated features (37 out of 42) identified using the MDF-SIT combination were also successfully identified using our approach. Of the 143 validated features identified by both approaches, 74 had a proposed structure of an ROS-structure-related metabolite; the other 34 features that contained a specific fragment of ROS metabolites were considered possible ROS metabolites. Interestingly, numerous ROS-structure-related metabolites were identified in this study, most of which were novel.Conclusion: The results reveal that the proposed approach can effectively and comprehensively identify ROS metabolites.https://www.frontiersin.org/articles/10.3389/fphar.2023.1293540/fulldose-response relationshipmetabolomicstime-course experimentrosiglitazonestable isotope tracing |
| spellingShingle | I-Shou Lin Chia-Ying Anderin Chuang Chia-Lung Shih Dose-response technique combined with stable isotope tracing for drug metabolite profiling by using high-resolution mass spectrometry Frontiers in Pharmacology dose-response relationship metabolomics time-course experiment rosiglitazone stable isotope tracing |
| title | Dose-response technique combined with stable isotope tracing for drug metabolite profiling by using high-resolution mass spectrometry |
| title_full | Dose-response technique combined with stable isotope tracing for drug metabolite profiling by using high-resolution mass spectrometry |
| title_fullStr | Dose-response technique combined with stable isotope tracing for drug metabolite profiling by using high-resolution mass spectrometry |
| title_full_unstemmed | Dose-response technique combined with stable isotope tracing for drug metabolite profiling by using high-resolution mass spectrometry |
| title_short | Dose-response technique combined with stable isotope tracing for drug metabolite profiling by using high-resolution mass spectrometry |
| title_sort | dose response technique combined with stable isotope tracing for drug metabolite profiling by using high resolution mass spectrometry |
| topic | dose-response relationship metabolomics time-course experiment rosiglitazone stable isotope tracing |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1293540/full |
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