ABSTRACT
Although Accelerator Mass Spectrometry (AMS) offers unparalleled sensitivity by investigating the fate of 14C-labeled compounds within the organism, its widespread use in ADME (absorption, distribution, metabolism, excretion) studies is limited. Conventional approaches based on Liquid Scintillation Counting (LSC) are still preferred, in particular because of complexity and costs associated with AMS measurements. Progress made over the last decade towards more compact AMS systems increased the interest in a combustion-based AMS approach allowing the analysis of samples in gaseous form. Thus, a novel gas Double Trap Interface (DTI) was designed, providing high sample throughput for the analysis of biomedical samples. DTI allows the coupling of an Elemental Analyzer (EA) for sample combustion to the hybrid ion source of a MICADAS (MIni CArbon DAting System) AMS system. The performance was evaluated in two studies through the analysis of more than 1000 samples from 14C-labeled biomatrices and fractions collected after liquid chromatography (LC). The covered activity ranged from 1 to 1000 mBq/g for labeled biomatrices and from 1 to 10000 mBq/g(C) for LC fractions. The implemented routine allows automated measurements requiring less than 5 min per sample (12-13 analyses per hour) without the need for sample conversion to graphite.
Subject(s)
Pharmaceutical Preparations , Pharmacokinetics , Carbon Radioisotopes , Gas Chromatography-Mass Spectrometry/methods , High-Throughput Screening Assays/instrumentation , High-Throughput Screening Assays/methods , Humans , Isotope Labeling/methods , Pharmaceutical Preparations/analysis , Pharmaceutical Preparations/metabolism , Scintillation Counting/methodsABSTRACT
Recently, it has been confirmed that extreme solar proton events can lead to significantly increased atmospheric production rates of cosmogenic radionuclides. Evidence of such events is recorded in annually resolved natural archives, such as tree rings [carbon-14 (14C)] and ice cores [beryllium-10 (10Be), chlorine-36 (36Cl)]. Here, we show evidence for an extreme solar event around 2,610 years B.P. (â¼660 BC) based on high-resolution 10Be data from two Greenland ice cores. Our conclusions are supported by modeled 14C production rates for the same period. Using existing 36Cl ice core data in conjunction with 10Be, we further show that this solar event was characterized by a very hard energy spectrum. These results indicate that the 2,610-years B.P. event was an order of magnitude stronger than any solar event recorded during the instrumental period and comparable with the solar proton event of AD 774/775, the largest solar event known to date. The results illustrate the importance of multiple ice core radionuclide measurements for the reliable identification of short-term production rate increases and the assessment of their origins.
ABSTRACT
AIM: Although regulatory guidances require human metabolism information of drug candidates early in the development process, the human mass balance study (or hADME study), is performed relatively late. hADME studies typically involve the administration of a 14C-radiolabelled drug where biological samples are measured by conventional scintillation counting analysis. Another approach is the administration of therapeutic doses containing a 14C-microtracer followed by accelerator mass spectrometry (AMS) analysis, enabling hADME studies completion much earlier. Consequently, there is an opportunity to change the current drug development paradigm. MATERIALS & METHODS: To evaluate the applicability of the MICADAS-cAMS method, we successfully performed: the validation of MICADAS-cAMS for radioactivity quantification in biomatrices and, a rat ADME study, where the conventional methodology was assessed against a microtracer MICADAS-cAMS approach. RESULTS & DISCUSSION: Combustion AMS (cAMS) technology is applicable to microtracer studies. A favorable opinion from EMA to complete the hADME in a Phase I setting was received, opening the possibilities to change drug development.
Subject(s)
Carbon Radioisotopes/blood , Carbon Radioisotopes/pharmacokinetics , Carbon Radioisotopes/urine , Pyridines/blood , Pyridines/pharmacokinetics , Pyridines/urine , Pyrimidines/blood , Pyrimidines/pharmacokinetics , Pyrimidines/urine , Animals , Carbon Radioisotopes/administration & dosage , Drug Discovery , Feces/chemistry , Humans , Male , Mass Spectrometry , Metabolome , Pyridines/administration & dosage , Pyrimidines/administration & dosage , Radioactive Tracers , Rats , Rats, Wistar , Scintillation Counting , Sensitivity and SpecificityABSTRACT
The problem of fraud continues to plague the wine industry, and detecting cases where the original bottle has been refilled with an inferior vintage is especially difficult. A novel noninvasive procedure presented here relies on radiocarbon dating the so-called angel's share: the trace amounts of ethanol and other gases that diffuse into and through the cork as bottled wine ages and matures. These are collected by applying a vacuum to the top of the bottle and cryo-trapping the extracted gas, leaving the liquid contents untouched. Vintage verification is therefore possible without exposing the liquid contents to the atmosphere, which may render a bottle costing tens of thousands of dollars worthless for later resale and consumption. The method also has a potential for stable isotope ratio as well as chemical analysis to find indications for fraud or spoilage of fine and rare wines as well as other liquids with cork stoppers.
ABSTRACT
The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (~3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.