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Major signal suppression from metal ion clusters in SFC/ESI-MS: Cause and Effects
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.ORCID iD: 0000-0002-1889-0668
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. National Veterinary Institute (SVA), Dept. of Chemistry, Environment and Feed Hygiene, Uppsala, Sweden.ORCID iD: 0000-0001-8962-2815
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Medical Products Agency, Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
2018 (English)In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 1084, p. 96-105Article in journal (Refereed) Published
Abstract [en]

The widening application area of SFC-MS with polar analytes and water-containing samples facilitates the use of quick and simple sample preparation techniques such as “dilute and shoot” and protein precipitation. This has also introduced new polar interfering components such as alkali metal ions naturally abundant in e.g. blood plasma and urine, which have shown to be retained using screening conditions in SFC/ESI-TOF-MS and causing areas of major ion suppression. Analytes co-eluting with these clusters will have a decreased signal intensity, which might have a major effect on both quantification and identification. When investigating the composition of the alkali metal clusters using accurate mass and isotopic pattern, it could be concluded that they were previously not described in the literature. Using NaCl and KCl standards and different chromatographic conditions, varying e.g. column and modifier, the clusters proved to be formed from the alkali metal ions in combination with the alcohol modifier and make-up solvent. Their compositions were [(XOCH3)n+X]+, [(XOH)n+X]+, [(X2CO3)n+X]+ and [(XOOCOCH3)n+X]+ for X= Na+ or K+ in ESI+. In ESI-, the clusters depended more on modifier, with [(XCl)n+Cl]- and [(XOCH3)n+OCH3]- mainly formed in pure methanol and [(XOOCH)n+OOCH]- when 20 mM NH4Fa was added.

To prevent the formation of the clusters by avoiding methanol as modifier might be difficult, as this is a widely used modifier providing good solubility when analyzing polar compounds in SFC. A sample preparation with e.g. LLE would remove the alkali ions, however also introducing a time consuming and discriminating step into the method. Since the alkali metal ions were retained and affected by chromatographic adjustments as e.g. mobile phase modifications, a way to avoid them could therefore be chromatographic tuning, when analyzing samples containing them.

Place, publisher, year, edition, pages
2018. Vol. 1084, p. 96-105
Keywords [en]
SFC-MS, matrix effect, alkali metal, ion cluster, Supercritical fluid chromatography, ESI
National Category
Analytical Chemistry
Research subject
Analytical Pharmaceutical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-345978DOI: 10.1016/j.jchromb.2018.03.024ISI: 000430524400012PubMedID: 29579734OAI: oai:DiVA.org:uu-345978DiVA, id: diva2:1190090
Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2018-06-26Bibliographically 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
Keywords
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)
Opponent
Supervisors
Available from: 2018-04-17 Created: 2018-03-15 Last updated: 2018-10-08

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Haglind, AlfredHedeland, MikaelArvidsson, TorbjörnPettersson, Curt E

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