| 1. |
- Barclay, Victoria K. H., et al.
(author)
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Acidic transformation of nordiazepam can affect recovery estimate during trace analysis of diazepam and nordiazepam in environmental water samples by liquid chromatography-tandem mass spectrometry
- 2019
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In: Analytical and Bioanalytical Chemistry. - : SPRINGER HEIDELBERG. - 1618-2642 .- 1618-2650. ; 411:17, s. 3919-3928
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Journal article (peer-reviewed)abstract
- In this study, a special interest was focused on the stability of diazepam and nordiazepam in aqueous samples at acidic and neutral pH. The aim of the study was to isolate and illustrate one of the many possible sources of error that can be encountered when developing and validating analytical methods. This can be of particular importance when developing multi-analyte methods where there is limited time to scrutinize the behavior of each analyte. A method was developed for the analysis of the benzodiazepines diazepam and nordiazepam in treated wastewater. The samples were extracted by solid phase extraction, using SPEC C18AR cartridges, and analyzed by the use of liquid chromatography, with a C18 stationary phase, coupled to tandem mass spectrometry. Environmental water samples are often acidified during storage to reduce the microbial degradation of the target compounds and to preserve the sample. In some cases, the samples are acidified before extraction. In this study, it was found that a chemical equilibrium between nordiazepam and a transformation product could cause inaccurately high extraction recovery values when the samples were stored at low sample pH. The stability of nordiazepam was shown to be low at pH3. Within 12days, 20% of the initial concentration of nordiazepam was transformed. Interestingly, the transformed nordiazepam was shown to be regenerated and reformed to nordiazepam during sample handling. At a sample pH of 7, diazepam and nordiazepam were stable for 12days. It was concluded that great care must be taken when acidifying water samples containing nordiazepam during storage or extraction. The storage and the extraction should be conducted at neutral pH if no internal standard is used to compensate for degradation and conversion of nordiazepam. The developed method was validated in treated wastewater and applied for the quantification of diazepam and nordiazepam in treated wastewater samples.
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| 2. |
- Fransson, Anette E, et al.
(author)
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Hydrogen Inhalation Protects against Ototoxicity Induced by Intravenous Cisplatin in the Guinea Pig
- 2017
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In: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 11
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Journal article (peer-reviewed)abstract
- Introduction: Permanent hearing loss and tinnitus as side-effects from treatment with the anticancer drug cisplatin is a clinical problem. Ototoxicity may be reduced by co-administration of an otoprotective agent, but the results in humans have so far been modest.Aim: The present preclinical in vivo study aimed to explore the protective efficacy of hydrogen (H2) inhalation on ototoxicity induced by intravenous cisplatin.Materials and Methods: Albino guinea pigs were divided into four groups. The Cispt (n = 11) and Cispt+H2 (n = 11) groups were given intravenous cisplatin (8 mg/kg b.w., injection rate 0.2 ml/min). Immediately after, the Cispt+H2 group also received gaseous H2 (2% in air, 60 min). The H2 group (n = 5) received only H2 and the Control group (n = 7) received neither cisplatin nor H2. Ototoxicity was assessed by measuring frequency specific ABR thresholds before and 96 h after treatment, loss of inner (IHCs) and outer (OHCs) hair cells, and by performing densitometry-based immunohistochemistry analysis of cochlear synaptophysin, organic transporter 2 (OCT2), and copper transporter 1 (CTR1) at 12 and 7 mm from the round window. By utilizing metabolomics analysis of perilymph the change of metabolites in the perilymph was assessed.Results: Cisplatin induced electrophysiological threshold shifts, hair cell loss, and reduced synaptophysin immunoreactivity in the synapse area around the IHCs and OHCs. H2 inhalation mitigated all these effects. Cisplatin also reduced the OCT2 intensity in the inner and outer pillar cells and in the stria vascularis as well as the CTR1 intensity in the synapse area around the IHCs, the Deiters' cells, and the stria vascularis. H2 prevented the majority of these effects.Conclusion: H2 inhalation can reduce cisplatin-induced ototoxicity on functional, cellular, and subcellular levels. It is proposed that synaptopathy may serve as a marker for cisplatin ototoxicity. The effect of H2 on the antineoplastic activity of cisplatin needs to be further explored.
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| 3. |
- Haglind, Alfred, 1986-, et al.
(author)
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Major signal suppression from metal ion clusters in SFC/ESI-MS : Cause and Effects
- 2018
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In: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 1084, s. 96-105
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Pierre, Pernilla Videhult, et al.
(author)
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Cisplatin-induced metabolome changes in serum : an experimental approach to identify markers for ototoxicity
- 2017
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In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 137:10, s. 1024-1030
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Journal article (peer-reviewed)abstract
- BACKGROUND: Ototoxicity from treatment with the anticancer drug cisplatin remains a clinical problem. A wide range of intracellular targets of cisplatin has been found in vivo.AIM: To investigate cisplatin-induced change of the serum metabolite profile and its association with ototoxicity.MATERIAL AND METHODS: Guinea pigs (n = 14) were treated with cisplatin (8 mg/kg b.w., i.v.) 30 min after administration of the otoprotector candidate sodium thiosulfate (group STS; n = 7) or sodium chloride (group NaCl; n = 7). Ototoxicity was evaluated by ABR (3-30 kHz) before and 4 d after drug treatment, and by assessment of hair cell loss. A blood sample was drawn before and 4 d after drug treatment and the polar metabolome in serum was analyzed using LC-MS.RESULTS: Cisplatin-treatment caused significant threshold elevations and outer hair cell (OHC) loss in both groups. The ototoxicity was generally lower in group STS, but a significant difference was reached only at 30 kHz (p = .007). Cisplatin treatment altered the metabolite profile significantly and similarly in both groups. A significant inverse correlation was found between L-acetylcarnitine, N-acetylneuraminic acid, ceramide, and cysteinylserine and high frequency hearing loss in group NaCl. The implication of these correlations should be explored in targeted studies.
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| 5. |
- Stenholm, Åke, et al.
(author)
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Removal of diclofenac from a non-sterile aqueous system using Trametes versicolor with an emphasis on adsorption and biodegradation mechanisms
- 2019
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In: Environmental technology. - : Informa UK Limited. - 0959-3330 .- 1479-487X. ; 40:19, s. 2460-2472
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Journal article (peer-reviewed)abstract
- This paper describes the search for procedures through which the xenobiotic pollutant diclofenac can be removed from non-sterile aquatic systems. Specifically, adsorption to solid supports (carriers) in combination with biodegradation by non-immobilized and immobilized white rot fungus Trametes versicolor were investigated. Batch experiments using polyurethane foam (PUF)-carriers resulted in 99.9% diclofenac removal after 4 h, with monolayer adsorption of diclofenac to carrier and glass surfaces accounting for most of the diclofenac decrease. Enzymatic reactions contributed less, accounting for approximately < 0.5% of this decrease. In bioreactor experiments using PUF-carriers, an initial 100% removal was achieved with biodegradation contributing approximately 7%. In batch experiments that utilized polyethylene-carriers with negligible immobilization of Trametes versicolor, a 98% total diclofenac removal was achieved after one week, with a biodegradation contribution of approximately 14%. Five novel enzyme-catalyzed biodegradation products were tentatively identified in the batch-wise and bioreactor experiments using full scan ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry. Both reduction and oxidation products were found, with the contents estimated to be at µg L-1 concentration levels.
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| 6. |
- Svan, Alfred, et al.
(author)
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Identification of transformation products from -blocking agents formed in wetland microcosms using LC-Q-ToF
- 2016
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In: Journal of Mass Spectrometry. - : Wiley. - 1076-5174 .- 1096-9888. ; 51:3, s. 207-218
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Journal article (peer-reviewed)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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| 7. |
- Svan, Alfred, et al.
(author)
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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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In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1409, s. 251-258
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Journal article (peer-reviewed)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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