| 1. |
- Josefsson, Martin
(författare)
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Studies on the enantioselective disposition of amlodipine : A challenge in bioanalysis
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To study the disposition of the enantiomers of the calcium channel blocker amlodipine in human plasma, an enantioselective high performance liquid chromatographic (HPLC) assay was developed. Several HPLC techniques such as chiral ion-pair forming, chiral derivatisation and direct separation on chiral columns were evaluated. A robust assay withhigh sensitivity for amlodipine's enantiomers, suitable for large scale analysis of plasma samples, was established by combining enantiomeric separation on Chiral-AGP i.e., an alfa1 acid glycoprotein material, with achiral HPLC using electrochemical detection, in a coupledcolumn system. The enantiomeric separation on the AGP material was evaluated andoptimised by performing chemometric i.e., multivariate analysis. Enantioselective pharmacokinetics, in healthy human subjects, after a single oral dose of amlodipine (Norvasc®) was shown. The pharmacologically active (S)-enantiomer was found in higher plasma concentrations than the (R)-enantiomer in all subjects, but the individual SIR ratios ranged from about 50:50 to 70:30. Comparable inter-individual differences in amlodipine concentration SIR ratio was found in patients during long-term treatment with Norvasc®. However, the changes over time, in the individual subjects, were low and were not significantly influenced if the dose was increased. A difference in systemic blood clearance of the two enantiomers is the most likely cause of the observed difference in pharmacokinetic behavior. At present, however, it cannot be discerned whether this is caused by differences in protein-binding or in intrinsic clearance of the unbound drug. Administration together with grapefruit juice was found to increase the amlodipine plasma concentrations in healthy volunteers without markedly change the plasma concentration SIR ratio. A nonstereoselective inhibition of the first-pass metabolism is proposed. Even though the effects seen were small the clinical significance of this food/drug interaction cannot be totally neglected since there are considerable differences seen between individuals.
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| 2. |
- Abrahamsson, Katarina, 1957, et al.
(författare)
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Organic bromine compounds produced in sea ice in Antarctic winter
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- During polar springtime, active bromine drives ozone, a greenhouse gas, to near-zero levels. Bromine production and emission in the polar regions have so far been assumed to require sunlight. Here, we report measurements of bromocarbons in sea ice, snow, and air during the Antarctic winter that reveal an unexpected new source of organic bromine to the atmosphere during periods of no sunlight. The results show that Antarctic winter sea ice provides 10 times more bromocarbons to the atmosphere than Southern Ocean waters, and substantially more than summer sea ice. The inclusion of these measurements in a global climate model indicates that the emitted bromocarbons will disperse throughout the troposphere in the southern hemisphere and through photochemical degradation to bromine atoms, contribute similar to 10% to the tropospheric reactive bromine budget. Combined together, our results suggest that winter sea ice could potentially be an important source of atmospheric bromine with implications for atmospheric chemistry and climate at a hemispheric scale.
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| 3. |
- Abujrais, Sandy, et al.
(författare)
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A sensitive method detecting trace levels of levonorgestrel using LC-HRMS
- 2019
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Ingår i: Contraception. - : Elsevier BV. - 0010-7824 .- 1879-0518. ; 100:3, s. 247-249
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop a high resolution mass spectrometry (HRMS) method to quantify levonorgestrel (LNG) in serum. Study design: Levonorgestrel was extracted using solid phase extraction and measured using liquid chromatography (LC) HRMS. Results: Low limit of quantification (LLOQ) was 25 pg/mL and low limit of detection (LLOD) was 12.5 pg/mL. Precision and accuracy bias were <10%. LNG in serum samples from Mirena® users ranged between 37 to 219 pg/mL (n=12). In eight out of 22 patients with suspected intrauterine device (IUD) expulsion LNG was detected (26–1272 pg/mL). Conclusion: A sensitive, fast and simple LC-HRMS method was developed to detect trace levels of LNG. © 2019 Elsevier Inc.
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| 4. |
- Ahnoff, Martin, et al.
(författare)
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Matrix effect explained by unexpected formation of peptide in acidified plasma
- 2015
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Ingår i: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199. ; 7:3, s. 295-306
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Peak distortion and strong signal enhancement was observed when applying a bioanalytical method based on mixed-mode SPE, hydrophilic interaction chromatography and ESI-MS to acidified rabbit plasma samples. Results: High-resolution ESI-MS and N-terminal peptide sequencing revealed a peptide NFQNAL, which was confirmed by H/D exchange ESI-MS. Conclusion: The peptide causing the observed matrix effect was formed by enzymatic degradation of serum albumin at pH 3. Degradation required both acidification and presence of other plasma constituents in addition to albumin to take place. The degree of signal enhancement correlated to the level of NFQNAL in the ion source as measured by MS, with a maximal enhancement factor of 3 at intermediate levels of NFQNAL. The interference was eliminated by changing to another type of hydrophilic interaction chromatography column.
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| 5. |
- Ahnoff, Martin, et al.
(författare)
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Thermal inactivation of enzymes and pathogens in biosamples for MS analysis
- 2015
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Ingår i: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199. ; 7:15, s. 1885-1899
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Tidskriftsartikel (refereegranskat)abstract
- Protein denaturation is the common basis for enzyme inactivation and inactivation of pathogens, necessary for preservation and safe handling of biosamples for downstream analysis. While heat-stabilization technology has been used in proteomic and peptidomic research since its introduction in 2009, the advantages of using the technique for simultaneous pathogen inactivation have only recently been addressed. The time required for enzyme inactivation by heat (approximate to 1 min) is short compared with chemical treatments, and inactivation is irreversible in contrast to freezing. Heat stabilization thus facilitates mass spectrometric studies of biomolecules with a fast conversion rate, and expands the chemical space of potential biomarkers to include more short-lived entities, such as phosphorylated proteins, in tissue samples as well as whole-blood (dried blood sample) samples.
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| 6. |
- Blessborn, D., et al.
(författare)
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Heat stabilization of blood spot samples for determination of metabolically unstable drug compounds
- 2013
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Ingår i: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199. ; 5:1, s. 31-39
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sample stability is critical for accurate analysis of drug compounds in biosamples. The use of additives to eradicate the enzymatic activity causing loss of these analytes has its limitations. Results: A novel technique for sample stabilization by rapid, high-temperature heating was used. The stability of six commercial drugs in blood and blood spots was investigated under various conditions with or without heat stabilization at 95 degrees C. Oseltamivir, cefotaxime and ribavirin were successfully stabilized by heating whereas significant losses were seen in unheated samples. Amodiaquine was stable with and without heating. Artemether and dihydroartemisinin were found to be very heat sensitive and began to decompose even at 60 degrees C. Conclusion: Heat stabilization is a viable technique to maintain analytes in blood spot samples, without the use of chemical additives, by stopping the enzymatic activity that causes sample degradation.
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| 7. |
- Granfors, Anna, 1978, et al.
(författare)
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Organic iodine in Antarctic sea ice: a comparison between winter in the Weddell Sea and summer in the Amundsen Sea
- 2014
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Ingår i: Journal of Geophysical Research - Biogeosciences. - 0148-0227 .- 2156-2202. ; 119:12, s. 2276-2291
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have recognized sea ice as a source of reactive iodine to the Antarctic boundary layer. Volatile iodinated compounds (iodocarbons) are released from sea ice, and they have been suggested to contribute to the formation of iodine oxide (IO), which takes part in tropospheric ozone destruction in the polar spring. We measured iodocarbons (CH3I, CH2ClI, CH2BrI and CH2I2) in sea ice, snow, brine and air during two expeditions to Antarctica, OSO 10/11 to the Amundsen Sea during austral summer, and ANT XXIX/6 to the Weddell Sea in austral winter. These are the first reported measurements of iodocarbons from the Antarctic winter. Iodocarbons were enriched in sea ice in relation to seawater in both summer and winter. During summer the positive relationship to Chl a biomass indicated a biological origin. We suggest that CH3I is formed biotically in sea ice during both summer and winter. For CH2ClI, CH2BrI and CH2I2 an additional abiotic source at the snow-ice interface in winter is suggested . Elevated air concentrations of CH3I and CH2ClI during winter indicate that they are enriched in lower troposphere and may take part in formation of IO at polar sunrise.
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| 8. |
- Marciani, L., et al.
(författare)
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Alginate and HM-pectin in sports-drink give rise to intra-gastric gelation in vivo
- 2019
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Ingår i: Food & Function. - : Royal Society of Chemistry. - 2042-6496 .- 2042-650X. ; 10:12, s. 7892-7899
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Tidskriftsartikel (refereegranskat)abstract
- The addition of gelling polysaccharides to sport-drinks may provide improved tolerability of drinks with high concentration of digestible carbohydrates (CHO), otherwise known to increase the risk of gastro-intestinal complaints among athletes under prolonged exercise. The physico-chemical properties of a drink containing 14 wt% of digestible CHO (0.7:1 fructose and maltodextrin-ratio), 0.2 wt% of HM-pectin/alginate and 0.06 wt%. sodium chloride were examined under in vitro gastric conditions using rheology and large deformation testing. The in vivo gelling behaviour of the drink was studied using magnetic resonance imaging of subjects at rest together with blood glucose measurements. The in vivo results confirm gelation of the test drink, with no gel remaining in the stomach at 60 min and blood glucose values were similar to control. The physico-chemical characterisation of the acidified test drink confirms the formation of a weak gel through which low Mw CHO can diffuse.
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| 9. |
- Nerentorp, Michelle, 1986, et al.
(författare)
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Antarctic winter mercury and ozone depletion events over sea ice
- 2016
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 129, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- During atmospheric mercury and ozone depletion events in the springtime in polar regions gaseous elemental mercury and ozone undergo rapid declines. Mercury is quicldy transformed into oxidation products, which are subsequently removed by deposition. Here we show that such events also occur during Antarctic winter over sea ice areas, leading to additional deposition of mercury. Over four months in the Weddell Sea we measured gaseous elemental, oxidized, and particulate-bound mercury, as well as ozone in the troposphere and total and elemental mercury concentrations in snow, demonstrating a series of depletion and deposition events between July and September. The winter depletions in July were characterized by stronger correlations between mercury and ozone and larger formation of particulate-bound mercury in air compared to later spring events. It appears that light at large solar zenith angles is sufficient to initiate the photolytic formation of halogen radicals. We also propose a dark mechanism that could explain observed events in air masses coming from dark regions. Br-2 that could be the main actor in dark conditions was possibly formed in high concentrations in the marine boundary layer in the dark. These high concentrations may also have caused the formation of high concentrations of CHBr3 and CH2I2 in the top layers of the Antarctic sea ice observed during winter. These new findings show that the extent of depletion events is larger than previously believed and that winter depletions result in additional deposition of mercury that could be transferred to marine and terrestrial ecosystems.
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| 10. |
- Nilsson, Lars B., et al.
(författare)
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Capillary microsampling in the regulatory environment : validation and use of bioanalytical capillary microsampling methods
- 2013
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Ingår i: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199. ; 5:6, s. 731-738
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Tidskriftsartikel (refereegranskat)abstract
- Capillary microsampling (CMS) has recently been introduced as a response to the demands for more ethical use of lab. animals according to the 3R principles. In CMS, an exact vol. of the blood, plasma or other biofluid is collected in a capillary from which it is washed out, resulting in a dild. sample that can be handled using the existing equipment in the bioanal. lab. CMS differs from traditional large vol. sampling as the microsample is dild. before further handling and anal., and reanal. is performed using the dild. sample. This has some implications for the validation and this report is an attempt to clarify how to validate and use CMS methods in a regulatory environment. CMS also shows some distinct new opportunities: labile analytes can be immediately stabilized at sample collection and the addn. of the internal std. to the whole sample can improve anal. performance. The experiences from 5 years use of CMS of plasma and blood for detn. of drug exposure in animal studies are reviewed.
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