Publications by authors named "Katsuya Ofuji"

Article Synopsis
  • P-NMR is easier to analyze than H-NMR, making it simpler to identify target signals for quantitation.
  • The study presents a method for determining the purity of brigatinib (BR), an organophosphorus compound, using quantitative P-NMR (P-qNMR) across multiple labs.
  • Results showed that the purity of BR was 97.94 ± 0.69% with P-qNMR, closely matching the 97.26 ± 0.71% found using H-qNMR, suggesting P-qNMR is a viable alternative for measuring organophosphorus compounds.
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  • The study examines the effectiveness of phosphorus quantitative NMR (P-qNMR) for measuring the purity of the drug sofosbuvir (SOF), as it offers clearer signals compared to hydrogen quantitative NMR (H-qNMR).
  • Soxfabuvir's purity was found to be 100.63% via P-qNMR and 99.07% via H-qNMR using methanol-d, highlighting numerical discrepancies likely due to overlapping signals in H-qNMR.
  • When switching to dimethyl sulfoxide-d (DMSO-d) as a solvent, P-qNMR yielded a SOF purity of 99.10%, which aligns closely with H
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  • Visible particles (VPs) in liquid monoclonal antibody formulations, particularly those containing poloxamer 188 as a surfactant, can cause quality issues due to their formation from protein and silicone oil aggregations.
  • This study identifies that VPs predominantly form when antibody solutions adhere to PDMS-coated stoppers in upright vials, leading to protein-PDMS aggregates that are later desorbed into the solution.
  • The research evaluated various factors influencing VP formation, such as the stopper's adhesion, storage orientation, coating, vial material, and PX188's hydrophobicity, revealing that altering any of these factors can significantly impact VP development.
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Recently, quantitative NMR (qNMR), especially H-qNMR, has been widely used to determine the absolute quantitative value of organic molecules. We previously reported an optimal and reproducible sample preparation method for H-qNMR. In the present study, we focused on a P-qNMR absolute determination method.

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Article Synopsis
  • Quantitative NMR (qNMR) is used to establish the absolute quantitative value of standards for HPLC-based quantification, specifically for hygroscopic substances like saikosaponin a and indocyanine green (ICG).
  • The study highlights the impact of humidity on the purity determination of ICG, noting that non-controlled humidity resulted in higher variation (86.12 ± 2.70%) and residual ethanol in the samples.
  • Using a controlled humidity environment, the purity of ICG decreased variability (84.19 ± 0.47%), and employing a constant temperature and humidity box minimized variation further (82.26 ± 0.19%), suggesting its use for standard reference preparation in JP
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Article Synopsis
  • NMR spectroscopy is being used to precisely measure organic molecules, with Hydrogen nucleus quantification (H qNMR) emerging as the primary method for assessing chemical purity.
  • A collaborative study involving 13 labs was conducted to validate the H qNMR method, measuring the purity of three samples certified by conventional methods.
  • Results showed that H qNMR measurements matched reference values closely, demonstrating its reliability and accuracy comparable to traditional measurement techniques.
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The azaspiracids (AZAs) are a group of marine toxins implicated in several intoxications whose mechanism of action is unknown. These phycotoxins include the five compounds shown in : AZA-1 (1), AZA-2 (2), AZA-3 (3), AZA-4 (4), and AZA-5 (5). The aim of this work was to study the effects of the five naturally occurring azaspiracids (AZA-1 to -5, Fig.

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Article Synopsis
  • Azaspiracids (AZs) are a newly identified group of toxins found along the coast of Ireland, with various analogues such as AZ-1 through AZ-5 and AZ-6 to AZ-11, which can cause gastrointestinal and neurotoxic symptoms.
  • The study focuses on AZ-4's effect on cytosolic calcium concentration in human lymphocytes, revealing that while AZ-4 doesn't affect resting Ca2+ levels, it inhibits the rise in Ca2+ induced by thapsigargin (Tg) in a dose-dependent manner.
  • The impact of AZ-4 seems specific to plasma membrane Ca2+ channels, as it reduces Ca2+ influx without influencing internal Ca2+ release,
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Azaspiracids (AZs) are a new group of phycotoxins discovered in the Ireland coast that includes the isolated analogues: AZ-1, AZ-2, AZ-3, AZ-4, and AZ-5 and the recently described AZ-6-11. Toxic episodes of AZs show gastrointestinal illness as in diarrhetic shellfish poisoning, but neurotoxic symptoms are also observed in a mouse bioassay. Despite their great importance in human health, so far, its mechanism of action is largely unknown.

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This paper reports on potential cellular targets of azaspiracid-1 (AZ-1), a new phycotoxin that causes diarrhoeic and neurotoxic symptoms and whose mechanism of action is unknown. In excitable neuroblastoma cells, the systems studied were membrane potential, F-actin levels and mitochondrial membrane potential. AZ-1 does not modify mitochondrial activity but decreases F-actin concentration.

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Toxicological effects of orally administered azaspiracid (AZA), a new toxin isolated from mussels, were investigated. First, a total of 25 mice were administered AZA twice at 300-450 microg/kg doses and observed for recovery processes from severe injuries. Slow recoveries from injuries were revealed: erosion and shortened villi persisted in the stomach and small intestine for more than 3 months: edema, bleeding, and infiltration of cells in the alveolar wall of the lung for 56 days; fatty changes in the liver for 20 days; and necrosis of lymphocytes in the thymus and spleen for 10 days.

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