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Identification of transformation products from -blocking agents formed in wetland microcosms using LC-Q-ToF
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, SE-75189 Uppsala, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Med Prod Agcy, Box 26, SE-75103 Uppsala, Sweden..
Univ Calif Berkeley, Dept Civil & Environm Engn, Berkeley, CA 94720 USA..
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2016 (English)In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 51, no 3, p. 207-218Article in journal (Refereed) Published
Resource type
Text
Abstract [en]

Identification of degradation products from trace organic compounds, which may retain the biological activity of the parent compound, is an important step in understanding the long-term effects of these compounds on the environment. Constructed wetlands have been successfully utilized to remove contaminants from wastewater effluent, including pharmacologically active compounds. However, relatively little is known about the transformation products formed during wetland treatment. In this study, three different wetland microcosm treatments were used to determine the biotransformation products of the -adrenoreceptor antagonists atenolol, metoprolol and propranolol. LC/ESI-Q-ToF run in the MSE and MS/MS modes was used to identify and characterize the degradation products through the accurate masses of precursor and product ions. The results were compared with those of a reference standard when available. Several compounds not previously described as biotransformation products produced in wetlands were identified, including propranolol-O-sulfate, 1-naphthol and the human metabolite N-deaminated metoprolol. Transformation pathways were significantly affected by microcosm conditions and differed between compounds, despite the compounds' structural similarities. Altogether, a diverse range of transformation products in wetland microcosms were identified and elucidated using high resolving MS. This work shows that transformation products are not always easily predicted, nor formed via the same pathways even for structurally similar compounds.

Place, publisher, year, edition, pages
2016. Vol. 51, no 3, p. 207-218
Keyword [en]
HRMS, wetland microcosms, transformation products, identification, LC-QToF, metoprolol, atenolol, propranolol
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-283784DOI: 10.1002/jms.3737ISI: 000372280300003PubMedID: 26956388OAI: oai:DiVA.org:uu-283784DiVA, id: diva2:919623
Available from: 2016-04-14 Created: 2016-04-14 Last updated: 2018-03-15Bibliographically approved
In thesis
1. Determination of the Environmental Fate of Drug Substances and the Matrix Effects of Complex Samples in SFC/ESI-MS
Open this publication in new window or tab >>Determination of the Environmental Fate of Drug Substances and the Matrix Effects of Complex Samples in SFC/ESI-MS
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Awareness of the potential problems caused by drug compounds in the environment has increased over the last decade, both among researchers and with the public. This thesis describes the development of analytical methods and their application to wetlands constructed for purification of wastewater from e.g. drug compounds. Different wetlands were investigated using microcosm-models, to determine their biodegradation. An enantioselective and sensitive SFC/ESI-QqQ method was developed and validated for the enantiomeric separation of atenolol, metoprolol, propranolol and metoprolol acid. It was applied measuring the enantiomeric fraction of the compounds in three different microcosm-models. The same microcosms were also used to investigate the transformation products formed in these wetlands. In this work, LC/ESI-QToF was used to identify the transformation products using standard references, the original compounds or analogs, comparing their accurate mass and product ions. One not previously observed major transformation product identified from propranolol were 1-naphthol. Several minor transformation products were also identified, showing how diverse the formation might be in wetlands.

A second part compares the matrix effect of ESI/MS using SFC and reversed phase LC, utilizing general screening methods for drug compounds in plasma, horse urine and influent/effluent wastewater. These matrices are known to suffer from matrix effects when using the ESI-source, and if SFC would suffer less than LC it could be a great benefit. The matrix profiles showed that this is likely not the case: although SFC was affected by different interferences then LC. One example is the formation of clusters causing major ion suppression. This unique SFC-phenomenon was investigated further, showing that metal ions were separated and eluted at different retention times, forming clusters in the ion source between metal ions and the organic modifier and/or make-up solvent.

In conclusion, the first part of this thesis describes analytical methods for determination of drug compounds in the environment, using LC and SFC, connected to both high and low resolving MS. The second part focuses on fundamental analytical chemistry, comparing the matrix effects of SFC/ESI-MS with LC/ESI-MS, and investigates the cluster phenomena observed for samples containing alkali ions and an organic modifier in the mobile phase in SFC/ESI-MS.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 44
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 252
Keyword
SFC-MS, matrix effect, ion cluster, Supercritical fluid chromatography; ESI, chiral separation, transformation products, LC-QToF, wetland microcosms
National Category
Analytical Chemistry
Research subject
Analytical Pharmaceutical Chemistry
Identifiers
urn:nbn:se:uu:diva-346164 (URN)978-91-513-0281-2 (ISBN)
Public defence
2018-05-09, B42, BMC, Husargatan 3, Uppsala, 09:15 (English)
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Supervisors
Available from: 2018-04-17 Created: 2018-03-15 Last updated: 2018-04-17

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Svan, AlfredHedeland, MikaelArvidsson, TorbjörnPettersson, Curt E.

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