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Accelerator Mass Spectrometry (accelerator + mass_spectrometry)
Selected AbstractsPhytochemical Research Using Accelerator Mass SpectrometryNUTRITION REVIEWS, Issue 10 2004Le T. Vuong PhD Vegetables and fruits provide an array of microchemicals in the form of vitamins and secondary metabolites (phytochemicals) that may lower the risk of chronic disease. Tracing these phytochemicals at physiologic concentrations has been hindered by a lack of quantitative sensitivity for chemically equivalent tracers that could be used safely in healthy people. Accelerator mass spectrometry is a relatively new technique that provides the necessary sensitivity (in attomoles) and measurement precision (<3%) towards 14Clabeled phytochemicals for detailed kinetic studies in humans at dietary levels. [source] Accelerator mass spectrometry offers new opportunities for microdosing of peptide and protein pharmaceuticalsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 10 2010Mehran Salehpour Accelerator Mass Spectrometry (AMS) is an ultra-sensitive analytical method which has been instrumental in developing microdosing as a strategic tool in early drug development. Considerable data is available for AMS microdosing using typical pharmaceutical drugs with a molecular weight of a few hundred Daltons. The so-called biopharmaceuticals such as proteins offer interesting possibilities as drug candidates; however, experimental data for protein microdosing and AMS is scarce. The analysis of proteins in conjunction with early drug development and microdosing is overviewed and three case studies are presented on the topic. In the first case study AMS experimental data is presented, for the measured concentration of orally administered recombinant insulin in the blood stream of laboratory rabbits. Case study 2 concerns minimum sample size requirements. AMS samples normally require about 1,mg of carbon (10,µL of blood) which makes AMS analysis unsuitable in some applications due to the limited availability of samples such as human biopsies or DNA from specific cells. Experimental results are presented where the sample size requirements have been reduced by about two orders of magnitude. The third case study concerns low concentration studies. It is generally accepted that protein pharmaceuticals may be potentially more hazardous than smaller molecules because of immunological reactions. Therefore, future first-in-man microdosing studies might require even lower exposure concentrations than is feasible today, in order to increase the safety margin. This issue is discussed based on the current available analytical capabilities. Copyright © 2010 John Wiley & Sons, Ltd. [source] Issues and opportunities in accelerator mass spectrometry for stable isotopesMASS SPECTROMETRY REVIEWS, Issue 5 2008Sam Matteson Abstract Accelerator mass spectrometry (AMS) has developed in the last 30 years many notable applications to the spectrometry of radioisotopes, particularly in radiocarbon dating. The instrumentation science of trace element AMS (TEAMS) that analyzes stable isotopes, also called Accelerator SIMS or MegaSIMS, while unique in many features, has also shared in many of these significant advances and has pushed TEAMS sensitivity to concentration levels surpassing many competing mass spectroscopic technologies. This review examines recent instrumentation developments, the capabilities of the new instrumentation and discernable trends for future development. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 27: 470,484, 2008 [source] Phytochemical Research Using Accelerator Mass SpectrometryNUTRITION REVIEWS, Issue 10 2004Le T. Vuong PhD Vegetables and fruits provide an array of microchemicals in the form of vitamins and secondary metabolites (phytochemicals) that may lower the risk of chronic disease. Tracing these phytochemicals at physiologic concentrations has been hindered by a lack of quantitative sensitivity for chemically equivalent tracers that could be used safely in healthy people. Accelerator mass spectrometry is a relatively new technique that provides the necessary sensitivity (in attomoles) and measurement precision (<3%) towards 14Clabeled phytochemicals for detailed kinetic studies in humans at dietary levels. [source] Accelerator mass spectrometry offers new opportunities for microdosing of peptide and protein pharmaceuticalsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 10 2010Mehran Salehpour Accelerator Mass Spectrometry (AMS) is an ultra-sensitive analytical method which has been instrumental in developing microdosing as a strategic tool in early drug development. Considerable data is available for AMS microdosing using typical pharmaceutical drugs with a molecular weight of a few hundred Daltons. The so-called biopharmaceuticals such as proteins offer interesting possibilities as drug candidates; however, experimental data for protein microdosing and AMS is scarce. The analysis of proteins in conjunction with early drug development and microdosing is overviewed and three case studies are presented on the topic. In the first case study AMS experimental data is presented, for the measured concentration of orally administered recombinant insulin in the blood stream of laboratory rabbits. Case study 2 concerns minimum sample size requirements. AMS samples normally require about 1,mg of carbon (10,µL of blood) which makes AMS analysis unsuitable in some applications due to the limited availability of samples such as human biopsies or DNA from specific cells. Experimental results are presented where the sample size requirements have been reduced by about two orders of magnitude. The third case study concerns low concentration studies. It is generally accepted that protein pharmaceuticals may be potentially more hazardous than smaller molecules because of immunological reactions. Therefore, future first-in-man microdosing studies might require even lower exposure concentrations than is feasible today, in order to increase the safety margin. This issue is discussed based on the current available analytical capabilities. Copyright © 2010 John Wiley & Sons, Ltd. [source] Accelerating drug development: methodology to support first-in-man pharmacokinetic studies by the use of drug candidate microdosingDRUG DEVELOPMENT RESEARCH, Issue 1 2007Matthew A. McLean Abstract Microdosing of experimental therapeutics in humans offers a number of benefits to the drug development process. Microdosing, conducted under an exploratory Investigational New Drug (IND) application, entails administration of a sub-pharmacological dose of a new chemical entity (NCE) that allows for early evaluation of human pharmacokinetics. Such information can be pivotal for: (1) selecting a compound for full drug development from a small group of candidates; (2) defining the amount of material needed for early development; and (3) setting the initial Phase I dose regimen in humans. Appropriate safety studies must be conducted to support microdosing in humans, but the requirements are generally less extensive than those needed to support a traditional IND. To date, microdosing has not been broadly applied by the pharmaceutical industry due to concerns about analytical sensitivity and the possibility of non-linear pharmacokinetics at extremely low doses. The primary method for detecting analytes following microdosing until now has been accelerator mass spectrometry, which is expensive, not generally available, and requires test agents to be radiolabeled. Presented in this report is an example of pharmacokinetics analysis using LC/MS/MS following microdosing of an experimental agent in cynomolgus monkeys. The results show good linearity in plasma pharmacokinetics for oral doses of 10,mg/kg (therapeutic dose) and 0.0005,mg/kg (microdose) of the test agent. The results also demonstrate the feasibility of applying standard laboratory analytics to support microdosing in humans and raise the possibility of establishing an animal model to screen for compounds having non-linear pharmacokinetics at low dose levels. Drug Dev. Res. 68:14,22, 2007. © 2007 Wiley-Liss, Inc. [source] Improved automated extraction and separation procedure for soil lipid analysesEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 2 2004G. L. B. Wiesenberg Summary Analysis of soil lipids may contribute to an improved understanding of atmosphere to soil carbon fluxes, soil organic matter source differentiation and pollutant accumulation. Soil lipids, mostly originating from plants and microorganisms, have traditionally been analysed by non-automated extraction and separation methods, which produce several lipid fractions, operationally defined by polarity. Here we present a combination of fast, automated and reproducible techniques, adopted from organic geochemical studies, for preparative separation of individual soil lipid fractions with increasing polarity. These techniques involve commercially available instruments, including accelerated solvent extraction and a two-step automated medium-pressure liquid chromatography procedure. The method yields eight lipid fractions consisting of five fractions fully amenable to gas chromatography/mass spectrometry (GC/MS) (aliphatic hydrocarbons, aromatic hydrocarbons, ketones, alcohols, carboxylic acids), and three fractions of highly polar or high molecular weight compounds (bases, very long-chain wax esters (C40+), high polarity compounds) that were not measurable with GC/MS under standard conditions. We tested the method on five agricultural soils. Results show that (i) mass recoveries for the individual fractions are reproducible, (ii) within individual fractions compound distribution patterns are reproducible, as demonstrated for alkanes and carboxylic acids, and (iii) individual fractions represent distinct and clean compound classes, free of interfering substances detectable by GC/MS. Thus, automated separation can be a fast, effective and reproducible procedure for fractionation of complex mixtures of soil lipids into clean compound classes, directly suitable for a variety of molecular (e.g. GC/MS) and isotopic characterizations (e.g. gas chromatography coupled with isotope ratio monitoring mass spectrometry or accelerator mass spectrometry). [source] Pollen- and diatom based environmental history since the Last Glacial Maximum from the Andean core Fúquene-7, ColombiaJOURNAL OF QUATERNARY SCIENCE, Issue 1 2003Maria Isabel Vélez Abstract The late Pleistocene,Holocene ecological and limnological history of Lake Fúquene (2580 m a.s.l.), in the Colombian Andes, is reconstructed on the basis of diatom, pollen and sediment analyses of the upper 7 m of the core Fúquene-7. Time control is provided by 11 accelerator mass spectrometry (AMS) 14C dates ranging from 19 670 ± 240 to 6040 ± 60 yr BP. In this paper we present the evolution of the lake and its surroundings. Glacial times were cold and dry, lake-levels were low and the area was surrounded by paramo and subparamo vegetation. Late-glacial conditions were warm and humid. The El Abra Stadial, a Younger Dryas equivalent, is reflected by a gap in the sedimentary record, a consequence of the cessation of deposition owing to a drop in lake-level. The early Holocene was warm and humid; at this time the lake reached its maximum extension and was surrounded by Andean forest. The onset of the drier climate prevailing today took place in the middle Holocene, a process that is reflected earlier in the diatom and sediment records than in the pollen records. In the late Holocene human activity reduced the forest and transformed the landscape. Climate patterns from the Late-glacial and throughout the Holocene, as represented in our record, are similar to other records from Colombia and northern South America (the Caribbean, Venezuela and Panama) and suggest that the changes in lake-level were the result of precipitation variations driven by latitudinal shifts of the Intertropical Convergence Zone. Copyright © 2003 John Wiley & Sons, Ltd. [source] Summary findings of the fourth international radiocarbon intercomparison (FIRI)(1998,2001)JOURNAL OF QUATERNARY SCIENCE, Issue 7 2002Elisabetta Boaretto Abstract Interlaboratory comparisons have been widely used in applied radiocarbon science. These are an important part of ongoing quality assurance (QA) programmes, which are vital to the appropriate interpretation of the evidence provided by the 14C record in Quaternary applications (including climate change and environmental reconstruction). International comparisons of laboratory performance are an essential component of the quality assurance process in radiocarbon dating. If the user community is to have confidence in radiocarbon results, it needs to be assured that laboratories world wide are producing measurements that are reliable and in accordance with ,good practice'. The findings from the most recent (completed in 2001) and extensive (more than 90 participating laboratories) radiocarbon intercomparison (FIRI) are reported here. This study was designed (i) to assess comparability, or otherwise, of the results from different laboratories and (ii) to quantify the extent and possible causes of any interlaboratory variation. The results demonstrate that there are no significant differences amongst the main measurement techniques (gas proportional counting, liquid scintillation counting and accelerator mass spectrometry (AMS)) but there is evidence of small laboratory offsets relative to known age samples for some laboratories. There is also evidence in some cases of underestimation of measurement precision. Approximately 10% of all results were classified as extreme (outliers) and these results were generated by 14% of the laboratories. Overall, the evidence supports the fact that radiocarbon laboratories are generally accurate and precise but that, notwithstanding internal QA procedures, some problems still occur, which can best be detected by participation in independent intercomparisons such as FIRI, where the results allow individual laboratories to assess their performance and to take remedial measures where necessary. The results from FIRI are significant in that they show a broad measure of agreement between measurements made in different laboratories on a wide range of materials and they also demonstrate no statistically significant difference between measurements made by radiometric or AMS techniques. Copyright © 2002 John Wiley & Sons, Ltd. [source] Issues and opportunities in accelerator mass spectrometry for stable isotopesMASS SPECTROMETRY REVIEWS, Issue 5 2008Sam Matteson Abstract Accelerator mass spectrometry (AMS) has developed in the last 30 years many notable applications to the spectrometry of radioisotopes, particularly in radiocarbon dating. The instrumentation science of trace element AMS (TEAMS) that analyzes stable isotopes, also called Accelerator SIMS or MegaSIMS, while unique in many features, has also shared in many of these significant advances and has pushed TEAMS sensitivity to concentration levels surpassing many competing mass spectroscopic technologies. This review examines recent instrumentation developments, the capabilities of the new instrumentation and discernable trends for future development. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 27: 470,484, 2008 [source] THE RADIOCARBON CHRONOLOGY OF KOPIA, AN EARLY GLASS MANUFACTURING CENTRE IN INDIAARCHAEOMETRY, Issue 5 2010A. K. KANUNGO Right from the time of the Painted Grey Ware (PGW) culture, dating to c. 1200,600 bce, more than 210 archaeological sites in India have provided evidence of glass, but there has been no attempt to date the glass-yielding layers by radiometric techniques. This has hampered the establishment of a chronology for the beginning and evolution of glass-making in India. The site of Kopia was excavated by the first author for three seasons from 2004 to 2006 to understand the history, development and technology of glass production in India. The excavation produced evidence of a long period of occupation, covering the Fine Grey Ware (FGW), Northern Black Polished Ware (NBP), Sunga,Kushana and Gupta periods. Twenty accelerator mass spectrometry (AMS) and radiocarbon dates, all derived from charcoal samples and processed independently by three laboratories, are available from the site. The dates range in their calibrated form on average from the ninth to the second century bce in locality I and from the second century bce to the second century ad in locality II. [source] 14C-dated fluctuations of the western flank of the Scandinavian Ice Sheet 45,25 kyr BP compared with Bølling,Younger Dryas fluctuations and Dansgaard,Oeschger events in GreenlandBOREAS, Issue 2 2010JAN MANGERUD Mangerud, J., Gulliksen, S. & Larsen, E. 2009: 14C-dated fluctuations of the western flank of the Scandinavian Ice Sheet 45,25 kyr BP compared with Bølling,Younger Dryas fluctuations and Dansgaard,Oeschger events in Greenland. Boreas, 10.1111/j.1502-3885.2009.00127.x. ISSN 0300-9483. We present 32 accelerator mass spectrometry (AMS) 14C dates obtained on well-preserved bones from caves in western Norway. The resulting ages of 34,28 14C kyr BP demonstrate that the coast was ice-free during the so-called Ålesund Interstadial. New AMS 14C dates on shells aged 41,38 14C kyr BP are evidence of an earlier (Austnes) ice-free period. The Ålesund Interstadial correlates with Greenland interstadials 8,7 and the Austnes Interstadial with Greenland interstadials 12,11. Between and after the two interstadials, the ice margin reached onto the continental shelf west of Norway. These events can be closely correlated with the Greenland ice core stratigraphy, partly based on identification of the Laschamp and Mono Lake palaeomagnetic excursions. We found that the pattern of the NGRIP ,18O curves for the two periods Greenland Interstadial (GI) 8 to Greenland Stadial (GS) 8 and GI 1,GS 1 (Bølling,Younger Dryas) were strikingly similar, which leads us to suggest that the underlying causes of these climate shifts could have been the same. We therefore discuss some aspects of glacial fluctuations during the Bølling,Younger Dryas in order to elucidate processes during Dansgaard,Oeschger events. [source] Holocene peat growth and decay dynamics in sub-arctic peat plateaus, west-central CanadaBOREAS, Issue 1 2009A. BRITTA K. SANNEL Peat and net carbon accumulation rates in two sub-arctic peat plateaus of west-central Canada have been studied through geochemical analyses and accelerator mass spectrometry (AMS) radiocarbon dating. The peatland sites started to develop around 6600,5900 cal. yr BP and the peat plateau stages are characterized by Sphagnum fuscum peat alternating with rootlet layers. The long-term peat and net carbon accumulation rates for both profiles are 0.30,0.31 mm/yr and 12.5,12.7 gC/m2yr, respectively. These values reflect very slow peat accumulation (0.04,0.09 mm/yr) and net carbon accumulation (3.7,5.2 gC/m2yr) in the top rootlet layers. Extensive AMS radiocarbon dating of one profile shows that accumulation rates are variable depending on peat plateau stage. Peat accumulation rates are up to six times higher and net carbon accumulation rates up to four times higher in S. fuscum than in rootlet stages. Local fires represented by charcoal remains in some of the rootlet layers result in very low accumulation rates. High C/N ratios throughout most of the peat profiles suggest low degrees of decomposition due to stable permafrost conditions. Hence, original peat accretion has remained largely unaltered, except in the initial stages of peatland development when permafrost was not yet present. [source] 10Be dating of Younger Dryas Salpausselkä I formation in FinlandBOREAS, Issue 4 2000SILVIO TSCHUDI Boulders of the Younger Dryas Salpausselkä I (Ss I) formation west of Lahti, southern Finland, were sampled for surface exposure dating. The 10Be concentrations, determined by accelerator mass spectrometry, yield minimum exposure ages of 11 930 ± 950, 11 220 ± 890, 11 050 ± 910 and 11 540 ± 990 years, using recently published production rates scaled for latitude and elevation. This includes a correction to the production rate resulting from postglacial uplift of the Fennoscandian lithosphere (i.e. changing elevation) during the time of exposure. The error-weighted mean exposure age of 11 420 ± 470 years of the analysed boulders agrees with previous varve dates of Ss I, which range from 11 680 to 11 430 calendar years BP. However, erosion has to be taken into account as a process affecting rock surfaces and therefore influencing exposure ages. Available information suggests an erosion rate of 5 mm/kyr, which increases the error-weighted mean exposure age to a value of 11 610 ± 470 years. Within the errors, the formation of Ss I in the Vesala area west of Lahti falls into the Younger Dryas time bracket, as defined by the GRIP and GISP 2 ice core (Greenland). [source] |