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- Svan, Alfred, et al.
(författare)
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Identification of transformation products from -blocking agents formed in wetland microcosms using LC-Q-ToF
- 2016
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Ingår i: Journal of Mass Spectrometry. - : Wiley. - 1076-5174 .- 1096-9888. ; 51:3, s. 207-218
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Svan, Alfred, 1986-, et al.
(författare)
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Matrix effects: Do they differ between SFC/ESI-MS and LC/ESI-MS
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction (120 ord)Supercritical fluid chromatography (SFC) is increasingly used in many fields following the new generation of instruments available on the market, often combined with electrospray ionization mass spectrometry (ESI/MS). New methods are developed and validated, often for samples of complex matrices. Thus, measurements of the matrix effects are sometimes included. Comparisons between SFC/ESI/MS and LC/ESI/MS have previously been performed, often focusing on e.g. sensitivity and separation. However, a systematic and qualitative investigation of the matrix effects achieved using same ion source and mass spectrometer, but different types of chromatography, i.e. SFC or LC, is so far lacking. Methods (120 ord)Effluent wastewater was collected and 100.0 ml was extracted using a generic SPE method (Oasis MCX), evaporated and redissolved in 1.0 ml of water:ACN (1:1). A 10 min gradient was developed for each technique, separating eight compounds chosen for being low molecular weight drugs with varying hydrophobicity and proteolytic properties. The mixture of compounds was then added to the ESI make-up solvent (MeOH) for the SFC/ESI/MS method. The extracted wastewater was injected without added compounds, and the SRM channel for each compound was monitored using tandem quadrupole MS (Quattro Micro, Waters®). The same interface and settings were used for LC, but an infusion of compounds was performed through a post-column syringe pump since no make-up flow was used. Preliminary data – Limit 300 wordsThe retention times for the eight model compounds were evenly spread over the chromatographic time scale for both chromatographic methods. When applying the continuous compound infusion through the make-up solution (SFC/ESI/MS) or through a syringe pump (LC/ESI/MS), a stable signal was observed for all compounds. Injection of the extracted wastewater affected the signal in comparison with the blank. The difference in the signal profiles were however larger between LC and SFC than between blank and extracted wastewater. The two separation techniques also gave different levels of noise and variations in the SRM-channels for the different compounds, and occurred at differently time points during the gradients for both the techniques. In summary, the matrix effects seem to affect the detection differently depending on what chromatographic technique that is used. With increased knowledge about this, it could help future method development to minimize the matrix effects. Novel aspect – Limit 20 wordsThe first systematic comparison between SFC and LC in terms of matrix effects for ESI-MS/MS using qualitative methods (infusion).
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- Svan, Alfred, et al.
(författare)
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Rapid chiral separation of atenolol, metoprolol, propranolol and the zwitterionic metoprolol acid using supercritical fluid chromatography-tandem mass spectrometry - Application to wetland microcosms
- 2015
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1409, s. 251-258
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Tidskriftsartikel (refereegranskat)abstract
- A method for enantiomeric separation of the three beta-blocking agents atenolol, metoprolol, propranolol and the zwitterionic metoprolol acid, a major metabolite of both metoprolol and in environmental matrices also atenolol, has been developed. By use of supercritical fluid chromatography and the polysaccharide-based Chiralpak (R) IB-3, all four compounds were simultaneously enantiomerically separated (R-s >1.5) within 8 min. Detection was performed using tandem mass spectrometry, and to avoid isobaric interference between the co-eluting metoprolol and metoprolol acid, the achiral column Acquity (R) UPC2 BEH 2-EP was attached ahead of to the chiral column. Carbon dioxide with 18% methanol containing 0.5% (v/v) of the additives trifluoroacetic acid and ammonia in a 2:1 molar ratio were used as mobile phase. A post column make-up flow (0.3 mL/min) of methanol containing 0.1% (v/v) formic acid was used to enhance the positive electrospray ionization. Detection was carried out using a triple quadrupole mass spectrometer operating in the selected reaction monitoring mode, using one transition per analyte and internal standard. The method was successfully applied for monitoring the enantiomeric fraction change over time in a laboratory scale wetland degradation study. It showed good precision, recovery, sensitivity and low effect of the sample matrix.
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- Svan, Alfred, 1986-, et al.
(författare)
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The differences in matrix effect between supercritical fluid chromatography and reversed phase liquid chromatography coupled to ESI/MS
- 2018
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Ingår i: Analytica Chimica Acta. - : ELSEVIER SCIENCE BV. - 0003-2670 .- 1873-4324. ; 1000, s. 163-171
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Tidskriftsartikel (refereegranskat)abstract
- For many sample matrices, matrix effects are a troublesome phenomenon using the electrospray ionization source. The increasing use of supercritical fluid chromatography with CO2 in combination with the electrospray ionization source for MS detection is therefore raising questions: is the matrix effect behaving differently using SFC in comparison with reversed phase LC? This was investigated using urine, plasma, influent-and effluent-wastewater as sample matrices. The matrix effect was evaluated using the post-extraction addition method and through post-column infusions. Matrix effect profiles generated from the post-column infusions in combination with time of flight-MS detection provided the most valuable information for the study. The combination of both qualitative and semi-quantitative information with the ability to use HRMS-data for identifying interfering compounds from the same experiment was very useful, and has to the authors' knowledge not been used this way before. The results showed that both LC and SFC are affected by matrix effects, however differently depending on sample matrix. Generally, both suppressions and enhancements were seen, with a higher amount of enhancements for LC, where 65% of all compounds and all sample matrices were enhanced, compared to only 7% for SFC. Several interferences were tentatively identified, with phospholipids, creatinine, and metal ion clusters as examples of important interferences, with different impact depending on chromatographic technique. SFC needs a different strategy for limiting matrix interferences, owing to its almost reverse retention order compared to RPLC.
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- Svan, Alfred, 1986-, et al.
(författare)
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The differences in matrix effects between supercritical fluid chromatography and reversed phase liquid chromatography coupled to ESI/MS analyzing blood plasma
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction The increasing popularity of supercritical fluid chromatography (SFC) in combination with electrospray ionization mass spectrometry (ESI/MS) within several fields calls for a deeper knowledge regarding this combination of techniques. The ESI source is known for its sensitivity regarding matrix effects, often a factor controlled during method development and validation using LC. The different chemistry and chromatographic selectivity of LC and SFC give potentially different impact on the ionization process in ESI; however, this an area still not well studied. Aim: To investigate how the matrix effects in ESI/MS differ for human plasma samples between SFC and reversed-phase LC, using generic screening conditions for both techniques, and a set of typical low molecular weight drug substances.Methods Pooled human plasma (500 µl) was precipitated using ice-cold acetonitrile (1000 µl). After mixing and centrifuging, 1200 µl of the supernatant were removed and evaporated at 40 ̊C. When dry, the samples were dissolved in 500µl water+0.1% FA (for LC) or acetonitrile:water 75:25 (for SFC). The samples were analyzed using SFC (Acquity UPC2, Waters®) and LC (Acquity UPLC, Waters®) and general screening conditions, using 10 min gradients. The same MS-system, a Q-ToF (Synapt G2-S, Waters®) acquiring in full scan mode, was used for detection with both separation techniques. The matrix effect was mainly evaluated using the Matrix Effect Profile, achieved from post-column compound infusions and injections of pretreated sample matrix and neat standards. From these data the average ME% was calculated for each data-point in the chromatogram, and through the full-scan mode using ToF, the compounds co-eluting with areas of suppression could be tentatively identified, suspected of creating the suppression. Results and discussion The Matrix Effect Profile-evaluation of the experiments, combining qualitative and quantitative information with the added ability to use HRMS-data to identify interfering compounds from the same experiments were most useful for our aim. Phospholipids, creatinine, polyethylene glycol and cluster formations are examples of important interferences co-eluting with areas of ion suppression, but with different impact depending on chromatographic technique. The results also showed several areas of enhancement using LC, an effect not seen using SFC.
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