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🗞️👉Publication Note 💥 🌐With the involvement of experts from Swissmedic, an international working group of representatives of regulatory authorities compiled data and principles that led to the development of a model for the risk assessment of nitrosamines based on chemical structural characteristics. This was published in a scientific journal. 🔍The article describes the principles of the Carcinogenic Potency Categorisation Approach (CPCA) published at the end of 2023. The method makes it possible to standardise the definition of acceptable intakes (AI) for medicinal products, including complex chemical nitrosamine impurities, specifically nitrosamine drug substance-related impurities" (NDSRI). This speeds up safety assessments of nitrosamine impurities. 📝The open-access scientific publication also uses sample molecules to illustrate how the CPCA is used to determine acceptable intakes for nitrosamine impurities. This allows industry and manufacturing experts in particular to understand the classification into different risk classes. 💡Not least, understanding the method enables constructive participation in its further development. In conjunction with other measures, the approach should also help to reduce or avoid animal experiments to assess the carcinogenic potential of nitrosamine impurities.

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Source: Analytical chemistry This article presents a sensitive and comprehensive method for analyzing signaling lipids using targeted liquid chromatography-mass spectrometry (LC-MS/MS). The method overcomes challenges such as a wide dynamic range, isomeric and isobaric species, and unwanted interaction along the separation path. It allows for the monitoring of 388 lipids in a single run of only 20 minutes and has been successfully applied to analyze the human plasma signaling lipidome and investigate lipid signaling pathways during platelet activation. This method provides unprecedentedly comprehensive analysis and direct insight into signaling pathways.

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🔬💡 Enhancing Drug Solubility Predictions in Organic Solvent Mixtures Using Machine Learning 🧪🧬 Navigating the complexities of drug solubility in organic solvents is critical for pharmaceutical development. This study by Francesca Cenci, Samir Diab , Paola Ferrini , Catajina Harabajiu , Massimiliano Barolo, Fabrizio Bezzo and Pierantonio Facco introduces a sophisticated machine-learning approach to predict drug solubility in solvent mixtures, leveraging high-throughput experimentation to refine solubility estimates for drug-like molecules. 📊 Utilizing a unique blend of supervised machine learning and quantitative structure–property relationship (QSPR) methodologies, the research focuses on the solubility of active pharmaceutical ingredients (APIs) as influenced by solvent molecular descriptors, functional subgroups, and mixture compositions. Partial Least-Squares (PLS) regression is employed to manage regressors' correlation, enhancing the precision of solubility predictions. Key Insights: 🔎 Advanced Solubility Modeling: Adopts a novel machine-learning framework that treats APIs as unique entities, improving solubility prediction across different solvent compositions and temperatures. 🧮 High Precision: Achieves determination coefficients ≥ 0.90 for solubility predictions in single, binary, and ternary solvent mixtures. 🔄 Validation Success: Tests the model against nine literature datasets of organic solubility, showing superior performance compared to benchmark models 🔍 Reduced Error Metrics: Demonstrates a significant reduction in RMSE ratio compared to benchmark models, confirming the method's robustness and accuracy. 🧪 Industry Application: Provides a scalable solution to predict solubility in industrially relevant solvents, supporting more effective crystallization processes. 📚 Link to Publication: https://lnkd.in/duWn6GhS #DrugSolubility #MachineLearning #Pharmaceuticals #ChemicalEngineering #Innovation #PolyModelsHub

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🔬 New Research article Alert! published in #DrugDevIndPharm 🌟 Stability-indicating green HPLC method for fixed-dose tablets containing remogliflozin etabonate and teneligliptin: an AQbD approach🌟 This study presents the development of a stability-indicating RP-HPLC method for quantifying remogliflozin etabonate and teneligliptin in fixed-dose tablets using an analytical quality by design (AQbD) approach. The method employs a HyperClone BDS C18 column with a mobile phase of acetonitrile and phosphate buffer. Risk assessment, Plackett-Burman design, and central composite design were used to optimize the method. Validation per ICH Q2(R1) guidelines demonstrated the method's accuracy, precision, and robustness. Forced degradation studies confirmed the method's stability-indicating nature. The AGREE score of 0.65 supports its green applicability for routine quality control analysis. This AQbD-assisted method offers efficient separation, environmental friendliness, and a simple mobile phase combination for analyzing this new fixed-dose combination in pharmaceutical formulations. 📖 Read the full article here: https://lnkd.in/gh-diY4r #HPLC #AnalyticalQualityByDesign #PharmaceuticalAnalysis #GreenChemistry #MethodDevelopment #QualityControl #Diabetes #FixedDoseCombination #Chromatography #DrugAnalysis

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Roles of the Chlorine and Methoxy Groups in Drug Discovery | https://lnkd.in/gpvXdSC9 Thu, Sep 26, 2024 8 AM PDT / 11 AM EDT / 5 PM CEST Small functional groups can greatly influence the interactions of a small-molecule ligand with the binding pocket of a protein or nucleic acid. Possible steps that a medicinal chemist could take to optimize a phenyl-containing hit molecule are summarized in the Topliss tree. The most important substituents that one encounters in this flowchart are chloro, methyl, and methoxy. Although the role of the methyl group has been highlighted in the literature and referred to as "magic methyl" to describe unexpectedly significant potency improvements, the roles of the chloro and methoxy groups in drugs has not been thoroughly explored. In this Flash Talk, Yoshihiro Ishihara will discuss the beneficial effects of chloro and methoxy substituents on intermolecular interactions, as well as the unique advantages and disadvantages of employing these substituents in drug discovery. Don’t miss this opportunity to learn about the groups often used in medicinal chemistry programs and engage with Yoshi in a Q&A session. Register here: https://lnkd.in/gpvXdSC9

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In a recent poster presentation from #WADC, we utilized the characteristics of the membrane absorbers, Sartobind® S and Phenyl, for aggregate and #payload clearance while polishing an #ADC in a single chromatographic run. The application of the tandem membrane chromatography system presented a novel and efficient purification scheme that was realized during ADC manufacturing. Access the poster here: https://lnkd.in/g5YWiTyw #CDMO #CRO #bioconjugation #drugdevelopment

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This most recent review primarily covers recent key advances in ADC history, clinical development status, molecule design, manufacturing processes, and quality control. The manufacturing process, especially the conjugation process, should be carefully developed, characterized, validated, and controlled throughout its lifecycle. The authors summarize the current challenges on ADC development and provide insightful perspectives. The corresponding author of this review article is Lan Wang who is the Head of Monoclonal Antibody Products at the Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control in China. She is also one of co-corresponding authors of another paper published in Antibody Therapeutics (2023 CiteScore: 8.7), the official journal of Chinese Antibody Society, published by Oxford University Press. The title of this paper is “Comparability strategy and demonstration for post-approval production cell line change of a bevacizumab biosimilar IBI305”. Open access to this paper at: https://lnkd.in/eNt287w9 #biologics #antibody #antibodies #antibodydiscovery #antibodytherapeutics #mab #mabs #cmc #bioprocess #biomanufacturing #processdevelopment #adc #adcs #antibodydrugconjugates #antibodydrugconjugate

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𝐓𝐡𝐞 𝐁𝐢𝐨𝐚𝐧𝐚𝐥𝐲𝐭𝐢𝐜𝐚𝐥 𝐓𝐞𝐬𝐭𝐢𝐧𝐠 𝐒𝐞𝐫𝐯𝐢𝐜𝐞𝐬 𝐌𝐚𝐫𝐤𝐞𝐭 𝐢𝐬 𝐁𝐨𝐨𝐦𝐢𝐧𝐠! The Global #Bioanalytical_Testing_Services_market is projected to grow at a CAGR of around 15.35% during the forecast period, 2023-28. The incessant need for Oral and Topical #Drugs due to a consistent surge in the diagnosis of diseases has resulted in their high production! This #growth is driven by factors like: 🔶𝐑𝐚𝐩𝐢𝐝 𝐝𝐢𝐚𝐠𝐧𝐨𝐬𝐭𝐢𝐜𝐬 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭: Earlier disease detection = more effective treatments. 🔶𝐑𝐢𝐬𝐢𝐧𝐠 𝐜𝐡𝐫𝐨𝐧𝐢𝐜 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬: Growing populations with conditions like diabetes and cancer require ongoing monitoring. 🔶𝐈𝐧𝐜𝐫𝐞𝐚𝐬𝐞𝐝 𝐝𝐫𝐮𝐠 𝐝𝐢𝐬𝐜𝐨𝐯𝐞𝐫𝐲: As pharmaceutical companies race to develop new drugs, bioanalytical testing becomes ever more crucial. 𝐆𝐞𝐭 𝐚 𝐂𝐨𝐦𝐩𝐥𝐢𝐦𝐞𝐧𝐭𝐚𝐫𝐲 𝐀𝐜𝐜𝐞𝐬𝐬 𝐭𝐨 𝐭𝐡𝐞 𝐅𝐨𝐫𝐞𝐜𝐚𝐬𝐭 𝐒𝐚𝐦𝐩𝐥𝐞 𝐑𝐞𝐩𝐨𝐫𝐭 (2024-30): https://lnkd.in/giy3mpSr 𝐊𝐞𝐲 𝐏𝐥𝐚𝐲𝐞𝐫𝐬- Charles River Laboratories, Medpace, ICON plc, WuXi Biologics, Eurofins Scientific, Syenos Health, SGS SA, Intertek, PPD Inc., Bioneeds India Pvt Ltd., CD BioSciences, Pace Analytical, BioAgilitix, Altasciences, Others #health #healthcare #heathcareindustry #bioanalyticaltesting #lifesciences #marketresearch #marketresearchreports #marketanalysis #marketgrowth #industryanalysis #industrygrowth #consulting #marknteladvisors 

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Identifying unknown #metabolites, often referred to as the "dark metabolome”: This article introduces a new metabolomics platform that combines “chemical tagging” and “tandem mass spectrometry”, leading to the discovery and identification of three new homocysteine metabolites! https://lnkd.in/eCFgpXtE The authors are currently working to identify an additional four putative homocysteine metabolites, highlighting the potential of this approach to significantly expand our understanding of this important pathway. Julius Agongo, Scott Grady, Kevin Cho, Gary Patti, Benjamin Bythell, Christopher Arnatt. #metabolome #darkmetabolome #massspectrometry #MS #research #analyticalchemistry #HRAMMS #ecoli

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Lipid nanoparticles (#LNPs) are not just a trend... Recent advancements in targeted lipid nanoparticles (#tLNPs) have focused on improving the precision and efficacy of drug delivery systems. With their unique physicochemical properties, LNPs can be finely tuned to meet specific therapeutic needs, enhancing efficacy and targeting capabilities. Understanding these characteristics is essential for maximizing their potential. Here’s what makes LNPs so effective: 🔷 𝗦𝗵𝗮𝗽𝗲 & 𝗖𝗿𝘆𝘀𝘁𝗮𝗹𝗹𝗶𝗻𝗶𝘁𝘆: LNPs can vary in shape and crystallinity, influencing their stability and drug release profiles. Tailoring these properties is crucial for optimizing performance. 🧪 𝗖𝗼𝗺𝗽𝗼𝘀𝗶𝘁𝗶𝗼𝗻 & 𝗠𝗮𝘁𝗲𝗿𝗶𝗮𝗹: The choice of lipids and surfactants affects particle size and stability, playing a critical role in how well the nanoparticles deliver drugs. 📏 𝗦𝗶𝘇𝗲 & 𝗦𝗶𝘇𝗲 𝗗𝗶𝘀𝘁𝗿𝗶𝗯𝘂𝘁𝗶𝗼𝗻: Typically ranging from 50 to 1000 nm, achieving a uniform size distribution is essential for consistent therapeutic outcomes. 🔗 𝗔𝗴𝗴𝗿𝗲𝗴𝗮𝘁𝗶𝗼𝗻 𝗦𝘁𝗮𝘁𝗲: Preventing aggregation is vital for maintaining a stable colloidal state, often achieved by optimizing lipid and surfactant concentrations. ⚖️ 𝗖𝗼𝗻𝗰𝗲𝗻𝘁𝗿𝗮𝘁𝗶𝗼𝗻: The concentration of LNPs directly impacts their therapeutic efficacy and stability, necessitating precise formulation techniques. 🌟 𝗦𝘂𝗿𝗳𝗮𝗰𝗲 𝗙𝘂𝗻𝗰𝘁𝗶𝗼𝗻𝗮𝗹 𝗚𝗿𝗼𝘂𝗽𝘀 & 𝗟𝗶𝗴𝗮𝗻𝗱𝘀: These features enhance interactions with biological membranes, improving cellular uptake and targeted delivery. ⚡ 𝗦𝘂𝗿𝗳𝗮𝗰𝗲 𝗖𝗵𝗮𝗿𝗴𝗲: A slightly negative zeta potential helps maintain stability and reduce aggregation, which is crucial for effective delivery. 🛡️ 𝗣𝗲𝗴𝘆𝗹𝗮𝘁𝗶𝗼𝗻 & 𝗖𝗼𝗮𝘁𝗶𝗻𝗴𝘀: Surface modifications like PEGylation extend circulation time and enhance biocompatibility, ensuring patient safety. 🏗️ 𝗣𝗼𝗿𝗼𝘀𝗶𝘁𝘆 & 𝗦𝘂𝗿𝗳𝗮𝗰𝗲 𝗔𝗿𝗲𝗮: These characteristics are key for drug loading and controlled release kinetics; amorphous LNPs often exhibit higher porosity. ------------------------------------- By mastering these characteristics, we can design more effective LNP-based systems. What insights or experiences do you have with lipid nanoparticles? We’d love to hear your thoughts! 💬 #LipidNanoparticles #LNPs #DrugDelivery #BiopharmaInnovation #TechnoPharmaSphere

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#CMI0324: Research & #Innovation World’s Most Comprehensive Protein Search Engine: Transforming Protein Discovery Processes for Industrial #Biocatalysis and Pharma #InnovationPitch: Interview with Johannes Kabisch (CSO), Joseph Heenan (CEO) and Aron Eiermann (CTO), Proteineer GmbH In the rapidly evolving field of #bioinformatics, the ability to access and analyze protein data is crucial for scientific advancement. While established tools have been instrumental in allowing researchers to find protein sequences, there are limitations, particularly when it comes to accessing novel data. Proteineer has developed a new search engine designed to bridge these gaps and provide a more comprehensive approach to protein discovery. CHEManager: What inspired you to create a new protein search engine? Johannes Kabisch: The realization that there are huge amounts of untapped sequence data besides the most commonly used Genbank. Our vision with Proteineer became to expand the accessibility for our customers to these already existing, yet very difficult to access data. Our search engine goes beyond just sequence similarity, we also use structural similarity and search through many data sources including short read archives thus including novel proteins that have not been previously discoverable. In short, with our approach we find far more #protein sequences than any other search engine. CMI: How many proteins do you typically find in a search? Joe Heenan: The number of proteins we identify depends on the search criteria, but it’s usually over 100,000 results. While this number seems large and unmanageable for testing, it is good to have more results to filter them for preferable properties. Once we find a protein, we predict its structure and various useful properties, such as thermostability, optimal operating temperatures, and expected expression levels in E. coli. We as well assess the structural similarity to the query protein and perform clustering. (...) CMI: What challenges did you face in developing and providing your services? Aron Eiermann: One of the major challenges was scaling our processes, which require really massive computational power, to be cost-effective for a larger customer base. This was solved by collaborating with the largest computational providers like OVH, Google, Amazon and NVIDIA. Another unexpected challenge was that the customers were overwhelmed by the amount of #sequencedata we could provide them, which was more than is readily testable in a lab. We have tackled this by developing a #software called GeneStore which allows our customers to use their expertise about their proteins to select a diverse panel they want to produce and characterize. (...) Read the full interview and more about Proteineer in our latest issue of CHEManager International: https://lnkd.in/ebD9dS7E

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𝗔 𝘁𝗵𝗲𝗿𝗺𝗼𝗱𝘆𝗻𝗮𝗺𝗶𝗰 𝗶𝗻𝘃𝗲𝘀𝘁𝗶𝗴𝗮𝘁𝗶𝗼𝗻 𝗶𝗻𝘁𝗼 𝗽𝗿𝗼𝘁𝗲𝗶𝗻–𝗲𝘅𝗰𝗶𝗽𝗶𝗲𝗻𝘁 𝗶𝗻𝘁𝗲𝗿𝗮𝗰𝘁𝗶𝗼𝗻𝘀 𝗶𝗻𝘃𝗼𝗹𝘃𝗶𝗻𝗴 𝗱𝗶𝗳𝗳𝗲𝗿𝗲𝗻𝘁 𝗴𝗿𝗮𝗱𝗲𝘀 𝗼𝗳 𝗽𝗼𝗹𝘆𝘀𝗼𝗿𝗯𝗮𝘁𝗲 𝟮𝟬 𝗮𝗻𝗱 𝟴𝟬 Developing stable biopharmaceutical formulations is of paramount importance and is typically achieved by incorporating surfactants as stabilising agents, such as polysorbate 20 and 80. However, little is known about the effect surfactant grade has on formulation stability. This study evaluates the effect of regular grade and Super-refined™ polysorbates 20 and 80 and their interaction with model proteins, namely β-lactoglobulin (β-Ig), human serum albumin (HSA) and immunoglobulin gamma (IgG), using isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). #excipient #polysorbates b Croda Pharma

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#AnalyticaMDPI Check the #Article 🧪Monitoring of a Broad Set of #Pharmaceuticals in #Wastewaters by High-Resolution Mass #Spectrometry and Evaluation of Heterogenous Catalytic Ozonation for Their Removal in a Pre-Industrial Level Unit ✍️by Anastasios Zouboulis et al. 🔗https://lnkd.in/gf3MyD4f

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#Inhibitors are important for the regulation of chemical processes in the body. Enzymes, proteins that speed up reactions, can be slowed or stopped by using inhibitors. This regulation allows different processes to be turned on or off when necessary. https://lnkd.in/gnMnMb2p

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