| 1. |
- Amini, Nahid, et al.
(författare)
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Feasibility of an on-line restricted access material/liquidchromatography/tandem mass spectrometry method in the rapid and sensitive determination of organophosphorustriesters in human blood plasma
- 2003
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Ingår i: Journal of chromatography. B. - 1570-0232 .- 1873-376X. ; 795:2, s. 245-256
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Tidskriftsartikel (refereegranskat)abstract
- A rapid on-line solid phase extraction/liquid chromatography/tandem mass spectrometry (SPE/LC/MS/MS) method usingrestricted access material (RAM) was developed for the simultaneous determination of eight organophosphorus triesters inuntreated human blood plasma. In a process involving column-switching techniques, the analytes were enriched on the RAMcolumn, separated using a C-18 analytical column and detected with LC/MS. Tandem mass spectrometrywas used to characterizeand quantify the analytes. To elucidate the fragmentation pathway of a number of the analytes, MS3 experiments using an iontrap mass spectrometer were performed. The matrix effects associated with using APCI and ESI interfaces were investigated.The recoveries obtained were in the range 60–92% (R.S.D. < 6%), with estimated detection limits between 0.2 and 1.8 ng/mlof plasma, and the total analysis time was 27 min.
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| 2. |
- Amini, Nahid, 1973-
(författare)
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Novel Solid Phase Extraction and Mass Spectrometry Approaches to Multicomponent Analyses in Complex Matrices
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Analysis of compounds present in complex matrices is always a challenge, which can be partly overcome by applying various sample preparation techniques prior to detection. Ideally, the extraction techniques should be as selective as possible, to minimize the concentration of interfering substances. In addition, results can be improved by efficient chromatographic separation of the sample components. The elimination of interfering substances is especially important when utilizing mass spectrometry (MS) as a detection technique since they influence the ionization yields. It is also important to optimize ionization methods in order to minimize detection limits.In the work this thesis is based upon, selective solid phase extraction (SPE) materials, a restricted access material (RAM) and graphitized carbon black (GCB) were employed for clean up and/or pre-concentration of analytes in plasma, urine and agricultural drainage water prior to liquid chromatography/mass spectrometry (LC/MS). Two SPE formats, in which GCB was incorporated in µ-traps and disks, were developed for cleaning up small and large volume samples, respectively. In addition, techniques based on use of sub-2 µm C18 particles at elevated temperatures and a linear ion trap (LIT) mass spectrometer were developed to improve the efficiency of LC separation and sensitivity of detection of 6-formylindolo[3,2-b]carbazole (FICZ) metabolites in human urine.It was also found that GCB can serve not only as a SPE sorbent, but also as a valuable surface for surface-assisted laser desorption ionization (SALDI) of small molecules. The dual functionality of GCB was utilized in a combined screening-identification/quantification procedure for fast elimination of negative samples. This may be particularly useful when processing large numbers of samples. SALDI analyses of small molecules was further investigated and improved by employing two kinds of new surfaces: oxidized GCB nanoparticles and silicon nitride.
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| 3. |
- Amini, Nahid, et al.
(författare)
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SALDI-MS Signal Enhancement Using Oxidized Graphitized Carbon Black Nanoparticles
- 2009
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Ingår i: Journal of the American Society for Mass Spectrometry. - : American Chemical Society (ACS). - 1044-0305 .- 1879-1123. ; 20:6, s. 1207-1213
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Tidskriftsartikel (refereegranskat)abstract
- The signal intensity of low-molecular-weight compounds analyzed using surface-assisted laserdesorption/ionization time-of-flight mass spectrometry (SALDI-TOF-MS) was significantlyenhanced when oxidized graphitized carbon black (GCB) particles were used as the desorption/ionization surface. The surface of oxidized GCB contains more carboxylic acid groupsthan non-oxidized GCB. Carboxylic acid groups enhance the efficiency of the ionizationprocess and the desorption of more hydrophobic compounds. A common pharmaceuticalcompound, propranolol, was successfully extracted from Baltic Sea blue mussels and quantifiedusing oxidized GCB as the SALDI surface, whereas deuterated propranolol was used asthe internal standard. The calibration curve showed a wide linear dynamic range of response(0.1–20 g/mL) and good reproducibility (RSD 10%). It was not possible to detectpropranolol in Baltic Sea blue mussels when non-oxidized GCB was used as the SALDI surface.
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| 4. |
- Amini, Nahid, et al.
(författare)
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Screening and Quantification of Pesticides in Water Using a Dual-Function Graphitized Carbon Black Disk
- 2010
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Ingår i: Analytical Chemistry. - : ACS. - 0003-2700 .- 1520-6882. ; 82:1, s. 290-296
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Tidskriftsartikel (refereegranskat)abstract
- A simple platform for combining solid phase extraction (SPE) and surface-assisted laser desorption ionization mass spectrometry (SALDI-MS) of extracted analytes, using disks prepared by embedding graphitized carbon black (GCB-4) particles in a network of polytetrafluoroethylene (PTFE), is presented. The system provides a convenient approach for rapid SALDI-MS screening of substances in aqueous samples, which can be followed by robust quantitative and/or structural analyses by liquid chromatography (LC)/MS/MS of positive samples. The extraction discs are easily transferred between gaskets where the sample extraction and desorption of selected samples is performed and the mass spectrometer. The SPE and SALDI properties of the new GCB-4 disc have been characterized for 15 pesticides with varying chemical properties, and the screening strategy has been applied to the analysis of pesticides in agricultural drainage water. Atrazine and atrazine-desethyl-2-hydroxy were detected in the sampled water by SALDI-MS screening and subsequently confirmed and quantified using LC/MS/MS.
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| 5. |
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| 6. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 7. |
- Rahman, Obaidur, et al.
(författare)
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Synthesis of ([C-11]carbonyl)raclopride and a comparison with ([C-11]methyl)raclopride in a monkey PET study
- 2015
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 42:11, s. 893-898
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The selective dopamine D-2 receptor antagonist raclopride is usually labeled with carbon-11 using [C-11]methyl iodide or [C-11]methyl triflate for use in the quantification of dopamine D-2 receptors in human brain. The aim of this work was to label raclopride at the carbonyl position using [C-11]carbon monoxide chemistry and to compare ([C-11]carbonyl)raclopride with ([C-11]methyl)raclopride in non-human primate (NHP) using PET with regard to quantitative outcome measurement, metabolism of the labeled tracers and protein binding. Methods: Palladium-mediated carbonylation using [C-11]carbon monoxide, 4,6-dichloro-2-iodo-3-methoxyphenol and (S)-(-)-2-aminomethyl-1-ethylpyrrolidine was applied in the synthesis of ([C-11]carbonyl)raclopride. The reaction was performed at atmospheric pressure using xantphos as supporting phosphine ligand and palladium (pi-cinnamyl) chloride dimer as the palladium source. ([C-11]Methyl)raclopride was prepared by a previously published method. In the PET study, two female cynomolgus monkeys were used under gas anesthesia of sevoflurane. A dynamic PET measurement was performed for 63 min with an HRRT PET camera after intravenous injection of ([C-11]carbonyl)raclopride and ([C-11]methyl)raclopride, respectively, during the same day. The order of injection of the two PET radioligands was changed between the two monkeys. The venous blood sample for measurement of protein binding was taken 3 min prior to the PET scan. Binding potential (BPND) of the putamen and caudate was calculated with SRTM using the cerebellum as a reference region. Results: The target compound ([C-11]carbonyl)raclopride was obtained with 50 +/- 5% decay corrected radiochemical yield and 95% radiochemical purity. The trapping efficiency (TE) of [C-11]carbon monoxide was 65 +/- 5% and the specific radioactivity of the final product was 34 +/- 1 GBq/mu mol after a 50 min of synthesis time. The radiochemical yield of ([C-11]methyl)raclopride was in the same range as published previously i.e. 50-60% and specific radioactivity of those two batches which were used in the present PET study were 192 GBq/mu mol and 638 GBq/mu mol respectively after a synthesis time of 32 min. In monkey PET studies, the percentage difference of BPND in putamen was <3% and that in caudate was <9% for the two radioligands. The plasma protein binding was 86.2 +/- 0.3% and 85.7 +/- 0.6% for ([C-11]carbonyl)raclopride and ([C-11]methyl)raclopride, respectively. The radiometabolite pattern was similar for both radioligands. Conclusion: Raclopride was C-11-labeled at the carbonyl position using a palladium-mediated [C-11]carbonylation reaction. A comparison between ([C-11]carbonyl)raclopride and ([C-11]merhyl)raclopride with regard to quantitative PET outcome measurements, metabolism of radioligands and protein binding in monkey was performed. The monkey PET study with ([C-11]carbonyl)raclopride showed similar results as for ([C-11]methyl)raclopride. The PET studies were performed on 2 subjects.
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| 8. |
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| 9. |
- Shariatgorji, Mohammadreza, et al.
(författare)
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Silicon nitride nanoparticles for surface-assisted laser desorption/ionization of small molecules
- 2009
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Ingår i: Journal of nanoparticle research. - : Springer Science and Business Media LLC. - 1388-0764 .- 1572-896X. ; 11:6, s. 1509-1512
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Tidskriftsartikel (refereegranskat)abstract
- Conventional matrix-assisted laser desorption/ionization mass spectrometry is limited to analyses of higher molecular weight compounds due to high background noise generated by the matrix in the lower mass region. Surface-assisted laser desorption/ionization (SALDI) mass spectrometry is an alternative solution to this problem. Nanoparticles, structured silicon surfaces and carbon allotropes are commonly used as SALDI surfaces. Here, for the first time, we demonstrate the application of silicon nitride nanoparticles as a suitable medium for laser desorption/ionization of small drug molecules.
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| 10. |
- Shariatgorji, Mohammadreza, 1974-, et al.
(författare)
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µ-trap for the SALDI-MS screening of organic compounds prior to LC/MS analysis
- 2008
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Ingår i: Analytical Chemistry. - : ACS. - 0003-2700 .- 1520-6882. ; 80:14, s. 5515-5523
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Tidskriftsartikel (refereegranskat)abstract
- A procedure for rapidly screening and quantitatively analyzing organic molecules is presented, in which a miniaturized solid-phase extraction (SPE) cartridge containing 0.6 mg of graphitized carbon black (the GCB-mu-trap) is used for sample pretreatment. Then surface-assisted laser desorption ionization dine-of-flight mass spectrometry (SALDI-TOF-MS) screening is followed by liquid chromatography/mass spectrometry (LC/MS) for robust quantitative analysis of samples containing analytes of interest. Liquid samples with volumes up to 100 mL were extracted using the GCB-mu-trap, and SALDI screening was performed by transferring a few particles of the GCB 4 sorbent from the mu-trap onto a stainless steel plate. Analytes were then simply ionized and desorbed by irradiating the GCB 4 particles without any further pretreatment. GCB 4 was found to be an excellent surface for the SALDI analysis of small molecules, providing spectra with very clean backgrounds. The small size of the cartridge (micropipet filter tip) results in enrichment of the analytes on a small surface area, affording low SALDI-TOF-MS detection limits. Furthermore, the removal of just a few particles from the p-trap does not significantly affect the subsequent quantitative determination. This approach offers considerable reductions in analytical costs by eliminating unnecessary SPE-LC/MS analyses.
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| 11. |
- Spacil, Zdenek, et al.
(författare)
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Matrix-less laser desorption/ionisation mass spectrometry of polyphenols in red wine
- 2009
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 23:12, s. 1834-1840
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Tidskriftsartikel (refereegranskat)abstract
- Matrix-assisted laser desorption/ionisation (MALDI) of small molecules is challenging and in most cases impossible due to interferences from matrix ions precluding analysis of molecules <300-500 Da. A common matrix such as ferulic acid belongs to an important class of compounds associated with antioxidant activity. If the shared phenolic structure is related to the propensity as an active MALDI matrix then it follows that direct laser desorption/ionisation should be possible for polyphenols. Indeed matrix-less laser desorption/ionisation mass spectrometry is achieved whereby the analyte functions as a matrix and was used to monitor low molecular weight compounds in wine samples. Sensitivity ranging from 0.12-87 pmol/spot was achieved for eight phenolic acids (4-coumaric, 4-hydroxybenzoic, caffeic, ferulic, gallic, protocatechuic, syringic, vanillic) and 0.02 pmol/spot for trans-resveratrol. Additionally, 4-coumaric, 4-hydroxybenzoic, caffeic, ferulic, gallic, syringic, vanillic acids and trans-resveratrol were identified in wine samples using accurate mass measurements consistent with reported profiles based on liquid chromatography (LC)/MS. Minimal sample pre-treatment make the technique potentially appropriate for fingerprinting, screening and quality control of wine samples. Copyright © 2009 John Wiley & Sons, Ltd.
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| 12. |
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| 13. |
- Wincent, Emma, et al.
(författare)
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The suggested physiologic aryl hydrocarbon receptor activator and cytochrome P4501 substrate 6-formylindolo[3,2-b]carbazole is present in humans
- 2009
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 284:5, s. 2690-2696
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Tidskriftsartikel (refereegranskat)abstract
- Dioxins and other polycyclic aromatic compounds formed during the combustion of waste and fossil fuels represent a risk to human health, as well as to the well being of our environment. Compounds of this nature exert carcinogenic and endocrine-disrupting effects in experimental animals by binding to the orphan aryl hydrocarbon receptor (AhR). Understanding the mechanism of action of these pollutants, as well as the physiological role(s) of the AhR, requires identification of the endogenous ligand(s) of this receptor. We reported earlier that activation of AhR by ultraviolet radiation is mediated by the chromophoric amino acid tryptophan (Trp), and we suggested that a new class of compounds derived from Trp, in particular 6-formylindolo[3,2-b]carbazole (FICZ), acts as natural high affinity ligands for this receptor. Here we describe seven new FICZ-derived indolo[3,2-b]carbazole-6-carboxylic acid metabolites and two sulfoconjugates, and we demonstrate the following. (i) FICZ is formed efficiently by photolysis of Trp upon exposure to visible light. (ii) FICZ is an exceptionally good substrate for cytochromes P450 (CYP) 1A1, 1A2, and 1B1, and its hydroxylated metabolites are remarkably good substrates for the sulfotransferases (SULTs) 1A1, 1A2, 1B1, and 1E1. Finally, (iii) sulfoconjugates of phenolic metabolites of FICZ are present in human urine. Our findings indicate that formylindolo[3,2-b]carbazols are the most potent naturally occurring activators of the AhR signaling pathway and may be the key substrates of the CYP1 and SULT1 families of enzymes. These conclusions contradict the widespread view that xenobiotic compounds are the major AhR ligands and CYP1 substrates.
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