Analytical Quality by Design-Compliant Development of a Cyclodextrin-Modified Micellar ElectroKinetic Chromatography Method for the Determination of Trimecaine and Its Impurities

In 2022, the International Council for Harmonisation released draft guidelines Q2(R2) and Q14, intending to specify the development and validation activities that should be carried out during the lifespan of an analytical technique addressed to assess the quality of medicinal products. In the present study, these recommendations were implemented in Capillary Electrophoresis method development for the quality control of a drug product containing trimecaine, by applying Analytical Quality by Design. According to the Analytical Target Profile, the procedure should be able to simultaneously quantify trimecaine and its four impurities, with specified analytical performances. The selected operative mode was Micellar ElectroKinetic Chromatography employing sodium dodecyl sulfate micelles supplemented with dimethyl-& beta;-cyclodextrin, in a phosphate-borate buffer. The Knowledge Space was investigated through a screening matrix encompassing the composition of the background electrolyte and the instrumental settings. The Critical Method Attributes were identified as analysis time, efficiency, and critical resolution values. Response Surface Methodology and Monte Carlo Simulations allowed the definition of the Method Operable Design Region: 21-26 mM phosphate-borate buffer pH 9.50-9.77; 65.0 mM sodium dodecyl sulfate; 0.25-1.29% v/v n-butanol; 21-26 mM dimethyl-& beta;-cyclodextrin; temperature, 22 & DEG;C; voltage, 23-29 kV. The method was validated and applied to ampoules drug products

LEGEND-1000 Preconceptual Design Report

We propose the construction of LEGEND-1000, the ton-scale Large Enriched Germanium Experiment for Neutrinoless $\beta \beta$ Decay. This international experiment is designed to answer one of the highest priority questions in fundamental physics. It consists of 1000 kg of Ge detectors enriched to more than 90% in the $^{76}$Ge isotope operated in a liquid argon active shield at a deep underground laboratory. By combining the lowest background levels with the best energy resolution in the field, LEGEND-1000 will perform a quasi-background-free search and can make an unambiguous discovery of neutrinoless double-beta decay with just a handful of counts at the decay $Q$ value. The experiment is designed to probe this decay with a 99.7%-CL discovery sensitivity in the $^{76}$Ge half-life of $1.3\times10^{28}$ years, corresponding to an effective Majorana mass upper limit in the range of 9-21 meV, to cover the inverted-ordering neutrino mass scale with 10 yr of live time

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Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Neutrinoless Double Beta Decay

This White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper

Neutrinoless Double Beta Decay

International audienceThis White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper

Neutrinoless Double Beta Decay

This White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper

Neutrinoless Double Beta Decay

This White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper

Neutrinoless Double Beta Decay

This White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper