Determination of Common Counterions and Impurity Anions in Pharmaceuticals Using a Capillary High Pressure Ion Chromatography System with Suppressed Conductivity and Charge Detection
Determination of Common Counterions and Impurity Anions in Pharmaceuticals Using a Capillary HPIC System with Suppressed Conductivity and Charge Detection
Recently, identification and quantification of ions in early stage drug development has gained increasing attention, because the APIs maybe contaminated with different counter ions from synthesis steps, and because selecting the counter ion to enhance APIs’ solubility and stability is becoming a key step in formulation development. This presentation demonstrates the identification and quantification of 22 commonly found anions in pharmaceuticals in a single run using a high-pressure capillary IC system (HPIC) with 4-μm particle ion –exchange column, and CD-QD dual detectors.
Introduction to High Performance Liquid Chromatography-HPLCRoyan Institute
This presentation is a simple explain of HPLC which introduce this method easily. You can use this PPTx File to present in your class and seminars as well. I prepare this file to present in Tabriz University of Medical Sciences when I was a MSc Medical Nanotechnology student. It will be useful for you too.
Join the experts as they discuss the use of accelerated solvent extraction and QuEChERS techniques for the extraction of pesticide residues from a diverse range of food samples. Tips and tricks for improving the extraction efficiency will be covered, along with selection criteria for each technique by sample type, assisting analysts in modifying existing methods or developing new methods to tackle their analytical challenges
LCMS is hyphenated technique. During Analytical method development analyst has to face many problems like Carry over ,matrix effect, adduct formation etc. For development of reproducible and robust analytical method “Troubleshooting is very essential”.
Introduction to High Performance Liquid Chromatography-HPLCRoyan Institute
This presentation is a simple explain of HPLC which introduce this method easily. You can use this PPTx File to present in your class and seminars as well. I prepare this file to present in Tabriz University of Medical Sciences when I was a MSc Medical Nanotechnology student. It will be useful for you too.
Join the experts as they discuss the use of accelerated solvent extraction and QuEChERS techniques for the extraction of pesticide residues from a diverse range of food samples. Tips and tricks for improving the extraction efficiency will be covered, along with selection criteria for each technique by sample type, assisting analysts in modifying existing methods or developing new methods to tackle their analytical challenges
LCMS is hyphenated technique. During Analytical method development analyst has to face many problems like Carry over ,matrix effect, adduct formation etc. For development of reproducible and robust analytical method “Troubleshooting is very essential”.
Stationary Phase and Mobile Phase Selection for Liquid Chromatography
The presentation focuses on how to choose the appropriate mode of separation, the correct column and highlights the importance of the correct mobile phase. This approach will be applied to a wide selection of compound types ranging from proteins, peptides, glycans to small pharmaceutical molecules and their metabolites. It will also look at specific application areas for monoclonal antibody analysis, namely: titer, aggregation, charge and oxidation variant. Platform methods for biologics characterization are also discussed.
1.Orthogonal” methods for analysis are needed in order to increase the probability that a primary assay has provided the separation (and recognition) of all peaks of interest.
2.A standardized procedure is described for the development of an “orthogonal” RP-LC separation , assuming that a primary RP-LC method for a given sample already exists.
3.An average change in resolution Rs > 3 for all adjacent peaks in the chromatogram seems likely (but not certain) to provide sufficient “orthogonality” to allow the recognition of any peaks in the “orthogonal” method that may have been overlapped and hidden in the primary method.
4.It has been demonstrated that HILIC provides different selectivity than RP-HPLC and is a useful tool for orthogonal method development.
5.Packed column SFC may provide higher separation efficiency and faster analyses with less consumption of organic solvent. SFC also offers chromatographic separation selectivity that is often similar to that of normal phase LC.
6.Results indicate that the CE method compares well with HPLC and can be used for the determination of carvedilol enantiomers in human serum. Although limits of quantitation are lower with HPLC, the CE assay offers the advantage of faster analysis times and low consumption of solvents
Monitoring and maintaining water purity are important to the power and electronics industries. In the both of these industries, impurities must be minimized and monitored to prevent corrosion or scaling, and degradation in demineralization processes. Learn about the analysis of ppb concentrations of ionic contaminants in high purity water using two easy methods: a direct large volume injection and concentration of a large volume injection, using electrolytically generated hydroxide eluents on a Reagent-Free™ Ion Chromatography system (RFIC™).
Stationary Phase and Mobile Phase Selection for Liquid Chromatography
The presentation focuses on how to choose the appropriate mode of separation, the correct column and highlights the importance of the correct mobile phase. This approach will be applied to a wide selection of compound types ranging from proteins, peptides, glycans to small pharmaceutical molecules and their metabolites. It will also look at specific application areas for monoclonal antibody analysis, namely: titer, aggregation, charge and oxidation variant. Platform methods for biologics characterization are also discussed.
1.Orthogonal” methods for analysis are needed in order to increase the probability that a primary assay has provided the separation (and recognition) of all peaks of interest.
2.A standardized procedure is described for the development of an “orthogonal” RP-LC separation , assuming that a primary RP-LC method for a given sample already exists.
3.An average change in resolution Rs > 3 for all adjacent peaks in the chromatogram seems likely (but not certain) to provide sufficient “orthogonality” to allow the recognition of any peaks in the “orthogonal” method that may have been overlapped and hidden in the primary method.
4.It has been demonstrated that HILIC provides different selectivity than RP-HPLC and is a useful tool for orthogonal method development.
5.Packed column SFC may provide higher separation efficiency and faster analyses with less consumption of organic solvent. SFC also offers chromatographic separation selectivity that is often similar to that of normal phase LC.
6.Results indicate that the CE method compares well with HPLC and can be used for the determination of carvedilol enantiomers in human serum. Although limits of quantitation are lower with HPLC, the CE assay offers the advantage of faster analysis times and low consumption of solvents
Monitoring and maintaining water purity are important to the power and electronics industries. In the both of these industries, impurities must be minimized and monitored to prevent corrosion or scaling, and degradation in demineralization processes. Learn about the analysis of ppb concentrations of ionic contaminants in high purity water using two easy methods: a direct large volume injection and concentration of a large volume injection, using electrolytically generated hydroxide eluents on a Reagent-Free™ Ion Chromatography system (RFIC™).
Similar to Determination of Common Counterions and Impurity Anions in Pharmaceuticals Using a Capillary High Pressure Ion Chromatography System with Suppressed Conductivity and Charge Detection
Analysis of Cations in Hydraulic Fracturing Flowback Water from the Marcellus Shale Using Ion Chromatography
This presentation describes the determination of cations in hydraulic fracturing flowback water using ion chromatography. In this work, sodium was most abundant, followed by calcium, strontium, magnesium, potassium, barium, ammonium, and then lithium, respectively. The quantity of scale-forming ions, such as calcium, strontium, and barium, is particularly informative because it can be used to determine the amount of anti-scaling agent in fracturing fluid mix that will maximize hydrocarbon recovery.
Adequacy and Efficacy of Treatment Plant Treating Electronics Industry Wastewater with the parameters : BOD, COD, TSS, TDS, Heavy Metals, Nitrogen and Phosphate.
Determination of Carbohydrates in Various Matrices by Capillary High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAE-PAD)
This presentation describes the combined advantages of a reagent-free capillary format Ion Chromatography (IC) to determine monosaccharides and disaccharides in various applications, from low concentrations in synthetic urine samples to high concentrations in beverage samples. In a reagent-free IC system, the hydroxide eluent is electrolytically generated inline to deliver accurate and precise concentrations for isocratic or gradient separations by only adding deionized water. Eluent generation eliminates carbonate contamination and errors from manual preparation. A capillary scale system with µL/min flow rates can run 24/7, always on and always ready for samples.
Analysis of Disinfection Byproducts by Ion Chromatography
In this presentation, the use of ion chromatography for the determination of bromate, chlorate and haloacetic acids for compliance monitoring according to various ISO standards (15061, 11206, 10304-4, 23631) and U.S. EPA Method 557 will be discussed. Examples will include IC methods using electrolytically generated hydroxide eluents on an RFIC™ system.
The importance of clean drinking water is recognized worldwide. In the U.S., the Environmental Protection Agency (EPA) has established Maximum Contamination Limits (MCL) for monitoring toxic contaminants that may cause adverse health effects. Other ions, such as chloride and sulfate are monitored for aesthetic characteristics under the U.S. National Secondary Drinking Water Standards guidelines. Similar regulations for clean drinking water have been implemented in other industrialized countries. Ion Chromatography (IC) methods have been approved for compliance monitoring including U.S. EPA 300.0 in 1993. Learn about using ion chromatography for the determination of inorganic anions, perchlorate and chromate for compliance monitoring according to U.S. EPA Methods 300.0, 314 and 218.6.
This webinar will provide pesticides residue analysts with valuable information on the development and optimization of chromatographic separations and mass spectrometry methods for the analysis of pesticide residues in food. The expert speakers will share their knowledge in understanding the critical aspects of the method, assisting analysts in optimizing their methods for the most challenging analyses.
This webinar will provide pesticides residue analysts with valuable information on the development and optimization of gas chromatographic separations and mass spectrometry methods for the analysis of pesticide residues in food. The expert speakers will share their knowledge in understanding the critical points of the method, assisting analysts in modifying existing methods, and understanding instrumental and software technologies with the goal of improving laboratory productivity and reducing the overall cost per sample. The results of experiments for both screening and quantification workflows, using the latest technology, will be presented.
Wastewater is produced by multiple sources, including chemical manufacturing, power generation, petroleum product extraction, and private residences. Specific industries can use knowledge of around the analytes present in wastewater to make decisions on reuse, treatment, or whether disposal is the most cost effective option. Prior to any discharge into ground or surface waters, the level of specific analytes must be determined to ensure that they do not exceed regulated limits. If these limits are being exceeded, treatment will be required. Ion Chromatography (IC) is the primary technique used for measuring the concentration of ions in wastewater and numerous methods have been developed that meet regulatory requirements. Learn about IC methods that enable accurate, consistent, and rapid measurement of both anions, such as chloride, sulfate, and bromate, and cations, such as sodium and magnesium.
In the past, measuring the total amount of an element was sufficient. Unfortunately, the effects of an element extend far beyond its absolute amount. Different forms of an element can exhibit very different physicochemical properties, including varying toxicities. The process of separation and quantification of different chemical forms of an element, more specifically termed speciation analysis, can be utilized to determine an element’s various chemical forms. The number of environmental applications of elemental speciation analysis has increased significantly. For example, both the United States EPA and the European Union have specified maximum admissible chromium concentrations in their respective drinking water directives and are evaluating the inclusion of hexavalent chromium in certain legislation. Learn about the latest developments in chromatography technology for speciation analysis that offer data for a wide variety of applications, including chromium in drinking water and both arsenic and sulfur in environmental waters.
The slickwater stimulation of unconventional gas and oil shale plays creates flowback water with a composition that is unique to particular shale formations. Characteristically, these fluids contain high concentrations of salts (e.g., chloride, bromide) which are routinely determined using ion chromatography. This analysis typically requires sample preparation, including manual dilution, which can significantly increase the cost of analysis. Results presented will show highly reproducible determination of anions and cations from Marcellus Shale flowback water using inline conductivity to identify high salt samples and then automatically diluting them prior to injection, saving time and column life.
Third edition INNPT Nano Particles in wastewater treatment presentation 30 s...Medhat Gad
using Nano particles in wastewater treatment to remove TSS,BOD,COD and pathogenic bacteria
INNPT stands for Innovative Nadic Nano particles Technology
our INNPT products works as chemical precipitation agent, Adsorbent with a huge surface area and very high negative charges
Determination of Elemental Impurities – Challenges of a Screening MethodSGS
On Dec. 16, 2014 the ICH Working Group published the elemental impurities guideline into the current version step 4. The aim of this control strategy is to track impurities that may contaminate pharmaceutical products that are potentially contributed by several sources. Additionally, the guideline also focuses on final drug product quality. To ensure that all components & all needed production steps required for a pharmaceutical product demonstrate regulatory compliance, risk assessment will become a priority for every pharmaceutical manufacturer. This approach of testing & documentation can become a major challenge, especially in the consideration of various potential sources.
Implementing a Fully Single-Use, Integrated mAb Biosimilars Purification Plat...MilliporeSigma
Access the interactive recording here: https://bit.ly/2DONZaQ
Webinar summary:
1000L-scale implementation of fully connected, disposable, advanced DSP platform for next generation mAb production.
Within the biopharmaceutical industry, there is a significant shift toward higher productivity processes resulting in improved economics without compromising robustness. Therefore, integrated continuous production technologies are of greatest interest.
Next Generation Biopharmaceutical Downstream Process is a European-funded collaborative project that aims at implementing a fully integrated manufacturing platform for biosimilar mAb based on continuous chromatography, in combination with single-use disposable technologies for all unit operations of DSP on pilot/small production scale together with incorporation of advanced analytical tools.
In this webinar, you will see:
* new DSP purification template producing > 3.3 kg of mAb in 2.5 days in less than 30m²
* proof of concept for the mAb manufacturing of tomorrow
Implementing a Fully Single-Use, Integrated mAb Biosimilars Purification Plat...Merck Life Sciences
Access the interactive recording here: https://bit.ly/2DONZaQ
Webinar summary:
1000L-scale implementation of fully connected, disposable, advanced DSP platform for next generation mAb production.
Within the biopharmaceutical industry, there is a significant shift toward higher productivity processes resulting in improved economics without compromising robustness. Therefore, integrated continuous production technologies are of greatest interest.
Next Generation Biopharmaceutical Downstream Process is a European-funded collaborative project that aims at implementing a fully integrated manufacturing platform for biosimilar mAb based on continuous chromatography, in combination with single-use disposable technologies for all unit operations of DSP on pilot/small production scale together with incorporation of advanced analytical tools.
In this webinar, you will see:
* new DSP purification template producing > 3.3 kg of mAb in 2.5 days in less than 30m²
* proof of concept for the mAb manufacturing of tomorrow
Today’s analytical laboratory is faced with tight deadlines to produce results from testing environmental samples. Too often, solid-phase extraction (SPE) presents a bottleneck in the analytical testing process and may cause poor analyte recoveries and highly variable. Despite advances in analytical instrumentation, sample prep often relies on tedious, manual, and expensive techniques such as liquid-liquid extraction.
Sample preparation of environmental water samples can be automated, however.. Use of automated sample preparation addresses the many challenges that laboratories face when preparing samples and can help improve sample processing turnaround times.
Chromatography presentation goes with this free on-demand webinar. Link to webinar: https://event.on24.com/eventRegistration/EventLobbyServlet?target=registration.jsp&eventid=832348&sessionid=1&key=7401504685427A0804ABBD1F956E617C&partnerrefthermo=undefined&sourcepage=register
Selectivity is the KEY
Mixed-mode chromatography addresses unmet challenges in pharmaceutical analysis:
API and counter ion by RP/AEX/CEX trimodal columns (e.g. Acclaim Trinity P1 and P2)
Unique Charged Aerosol Detector for consistent response of analytes that are weak or non-chromophoric molecules
Unmatched performance for counter ion analysis by dedicated column technology, unique charged aerosol detection and established UltiMate 3000 technology
New IonCount complete solution for ease of use and quick methods development of new API and counter ion analysis
Easy operation by predefined eWorkflows, Thermo Scientific™ Dionex™ Chromeleon™ 7.2 Chromatography Data System, and viper connection tubing
Presentation Outline
• Challenges in pharmaceutical analysis
• Mixed-mode chromatography overview
• Mixed-mode chromatography for pharmaceutical analysis
• API and counter ions
• Thermo Scientific™ Dionex™ Corona™ Veo™ Charged Aerosol Detector
• Near universal, mass sensitive detector for routine Liquid Chromatography determinations of any non-volatile and many semi-volatile analytes
• Ion-Count Solutions
• Unmatched performance for counter ion analysis by dedicated column
technology, unique charged aerosol detection and established Thermo
Scientific™ Dionex™ Ultimate™ 3000 High Performance Liquid Chromatography technology
•Summary
Similar to Determination of Common Counterions and Impurity Anions in Pharmaceuticals Using a Capillary High Pressure Ion Chromatography System with Suppressed Conductivity and Charge Detection (20)
This webinar will provide pesticides residue analysts with valuable information on software method development and data processing for the analysis of pesticide residues in food for both LC–MS and GC–MS. Technical experts will review the latest in software advances to help with data interpretation and reporting.
This presentation will focus on the new USP Chapter <2232> on elemental contaminants in dietary supplements. In particular, it will discuss the permitted daily exposure (PDE) limits of the four heavy metals of toxicological concern defined in the chapter and the different options for measurement strategies to meet these limits. In addition it will give an overview of the new USP Chapter <233>, which describes the suggested sample preparation, instrumental techniques and validation protocols required to demonstrate compliance of the analytical procedure used.
In this webinar Dr. Bertrand Rochat of Faculté de Biologie et de Médecine of the Centre Hospitalier Universitraire Vaudois (CHUV) at Lausanne discusses the paradigm shift to high resolution mass spectrometry (HRMS) in clinical research for quantitative analyses (sensitivity, selectivity, etc.). Quantifications in high resolution full scan or MS/MS mode will be compared with triple quadrupole MS. He will present Quan/Qual analysis with a study on the fate of an anti-cancer agent in human: with over 40 metabolites being identified and quantified; as well as metabolomics data underscoring the versatility of high resolution Orbitrap MS.
Many factors impacting the measurement precision of ICP-OES and ICP-MS are still often neglected for everyday operation, however. Sample preparation is one of the factors that play a crucial role in the success of high-quality sample analysis. In this webinar, our experts will discuss sample preparation to: 1) improve analysis precision 2) make difficult samples easy to be analyzed 3) eliminate sample dilution to minimize error introduction.
For more information, please visit here: http://chrom.ms/CtRtKpw
The webinar is all about Ultra High Pressure Liquid Chromatography (UHPLC) performance and how new column technology can deliver the best separation power and be married with the best UHPLC system to ensure an outstanding result. It covers how chromatographers can ensure that even very complex and unfamiliar samples are assayed with the highest scrutiny possible? The webinar discusses how to get the most out of solid core column technology with the right UHPLC system. It covers the use of an extremely long column approach for ultra-high resolution assays and the outlines the importance of robustness and retention time stability.
In the pharmaceutical arena there is great interest in solid core technology, where there is a broad range of sample types as well as requirements throughout the process of developing new chemical entities. The presentation looks at how solid core technology can be readily adapted to cope with the challenges associated with the pharmaceutical sector, looking at various sample matrices and molecular entities, from small molecules to large biomolecules. The presentation gives an insight into how varying the solid core to porous layer allows the user to optimize separation performance by reducing extra band broadening. Data presented demonstrates how this technology is more robust than fully porous systems when analyzing biological extracts, routinely used in DMPK departments, resulting in longer column lifetimes.
Investigation into the design and application of solid core stationary phases has led to a better understanding of how the phases work and has resulted in their design aligned to the structure of the analytes being separated. The current range of columns available is discussed both in terms of selectivities, and also morphologies, allowing informed decisions to be made by the chromatographer. Using real life examples, coupled with advanced modeling, the effects of the particle size and morphology will be given for both small and large molecules, offering an insight into what the future holds for solid core products.
Over the past decade, the number of mAb candidates entering the clinical pipeline has grown significantly. In addition, the number of ADCs that use mAb specificity to carry drug payloads to target sites has increased. As a result, analytical characterization is in high demand.
This webinar discusses new innovations in sample preparation, column technology, UHPLC, and high resolution mass spectroscopy (HRMS) that allow the development of analytical methods with run times of less than 5 minutes for all routine methods.
Over the past decade, there have been a growing number of mAb candidates entering the clinical pipeline. This results in a large increase on the demand for analytical characterization. This seminar discusses advances in analytical method development with analytical run times below 10 minutes for all routine methods with intelligent, integrated chromatography workflows. Orbitrap technology has been established as the most powerful MS technology for protein characterization. How this can be incorporated into a complete workflow for bio-pharma analysis is also discussed.
Overview of webinar:
Rechargeable, manganese-based, lithium-ion batteries (LiBs) are environmentally friendly, have a good safety record, and can be made at a lower cost than other metal-based LiBs. However, they have a shorter lifetime. Much research has been spent on improving product safety, cycle life, and product performance, yet understanding fundamental processes and degradation mechanism in LiBs remains a challenge. Identifying breakdown products and understanding degradation processes can lead to enhancing battery performance, improvements in product safety, and insight into component failure mechanisms.
Analysis of Anions and Cations in Produced Water from Hydraulic Fracturing Using Ion Chromatography
This presentation describes the use of ion chromatography (IC) to determine anions and cations in produced water from three different hydraulic fracturing sites. Considerable variation in ion concentration was found, which was attributed to differences in the geology of the locations from which samples were obtained.
High-performance anion-exchange chromatography with pulsed amperometric detection is valuable for oligosaccharide analysis with the value derived from the high-resolution separation followed by sensitive detection of native oligosaccharides. In this presentation the application of HPAE-PAD to oligosaccharides released from glycoproteins is demonstrated.
Total workflow solutions that cater every budget, performance or throughput requirement for confirmatory dioxin analysis were discussed in the Thermo Scientific Lunch Seminar at the Dioxin 2014 conference. D. Hope, CEO & Owner Pacific Rim Laboratoris, presented about the economies of POPs analysis from the point of view of a leading laboratory using the very latest dioxin method kits. C. Cojocariu, Thermo Fisher Scientific, discussed recent changes in EU regulations which bring new opportunities for more labs to participate in dioxin analysis and about validating methods using Gas Chromatography triple quadrupole for PCDD/Fs with reference to the new EU Commission Regulation No. 709/2014.
Different forms of an element can exhibit very different physicochemical properties, including varying toxicities. The chromatography process of separation and quantification of different chemical forms of an element, more specifically termed speciation analysis, can be utilized to determine an element’s various chemical forms. The food safety industries have significantly increased their interest in understanding an element’s various chemical forms due to pending legislative pressures. Learn about the latest developments in speciation technology and offer proof data for a wide variety of applications, including arsenic species in apple juice and rice syrup and iodine species in milk.
Modern business drivers are continually pushing to reduce the time it takes to get a product or service to market, reduce the risk and cost associated with that, and to improve quality.
In laboratories, delivering an analytical result that’s ‘right first time’ (RFT) is the answer. There is no reprocessing data or re-running injections and no out of specification (OOS) results or reporting/calculation errors.
Using chromatography data system tools for RFT analysis automatically gives high quality of results and confidence in results, lower cost of analysis, improved lab efficiency, and faster release to market and return on investment (ROI).
More from Chromatography & Mass Spectrometry Solutions (17)
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
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Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...
Determination of Common Counterions and Impurity Anions in Pharmaceuticals Using a Capillary High Pressure Ion Chromatography System with Suppressed Conductivity and Charge Detection
1. 1
Determination of Common Counterions
and Impurity Anions in
Pharmaceuticals Using a Capillary HPIC
System with Suppressed Conductivity
and Charge Detection
Hua Yang
Application Chemist
Thermo Fisher Scientific
The world leader in serving science
2. Outline
2
• Why ion analysis is important for the pharmaceutical
industry?
• The instrument used for the ion analysis: Why HPIC, capillary
and two detectors?
• Method of identified and quantified 22 anions in a single run
and its application
3. Drug Development is Lengthy and Costly
3
Drug R&D
~6 Years
~ 7 Years
1-2 Years
Drug discovery
~10,000 Compounds
Pre-clinical
~250
Clinical trials
~5
FDA review
<2
$1-5 billion and ~15 years to develop a new drug
4. Why is Ion Analysis Needed?
Fact: More than 50% of all pharmaceutical active ingredients
(APIs) are administered as salts
4
• Late stage: Compliance with FDA regulations
• Pharmaceutical products must be tested fro composition to verify their
identity, strength, quality, and purity
• Early stage: Development and selection of the best
formulation for late stage drug development
• Raw material quality control (counterion identity, stoichiometry
confirmation)
• Counterion screening to improve API properties such as solubility,
stability, and processiblity
5. Capillary HPIC System with Dual Detectors
Deionized water
18 MΩ-cm resistivity
Anion Trap Column
5
Data
Management
Waste
H20
Pump*
EGC*
CR-ATC*
Degas
Module*
ACES CRD
* High-pressure module up to 5000 psi
ASTC*
Non-Metallic Pump
Eluent Generator
Cartridge
Continuously-
Regenerated
Anion Trap Column
Auto sampler
Electrolytic
Eluent
Suppressor
Columns
Injection Valve
with internal
sample loop
Conductivity
Detector (CD)
Carbonate
Removal
Device
Charge
Detector (QD)
6. Why HPIC?
6
• Remember UHPLC?
• As the particle size decreases from 8 μm to 4 μm, the column
efficiency doubles
• This drop in particle size increases the column pressure by
4x
• Like HPLC, IC is moving towards smaller particle column
technology
• HPIC instrumentation can now handle the pressure of these
smaller particle columns, even at higher flow rates
7. HPIC Theory
7
Influence of the particle diameter on pressure and efficiency
100
0
0 2 4 6 8 10
Linear Velocity u [mm/s]
1200
1000
Column pressure [bar]
800
600
400
200
0
0 2 4 6 8 10
Linear Velocity u [mm/s]
10 μm particles
5 μm particles
3 μm particles
2 μm particles
Optimal flow rate for
maximum separation
efficiency/resolution
Theoretical Plate Height [μm]
Faster flows for faster separations generate higher pressure
Smaller particles for higher efficiency generate higher pressure
8. 8
High Efficiency Dionex IonPac 4 μm Particle IC Columns
Ion-exchange columns with 4 μm particle-size
Benefits
• Smaller particles provide better performance
• Faster run times with higher flow rates using 150 mm
columns
• Better resolution with standard flow rates using 250 mm
columns
High resolution using the
Dionex IonPac AS11-HC-4μm
column
Fast run using the
5.5
μS
Thermo Scientific™ Dionex™
IonPac™ AS18-4μm column
10
1 0 40
Minutes
μS
0 3
-0.5
5
μS
0
Minutes 0 40
Minutes
Applications
• Anions in environmental
waters
• Organic acids in foods and
beverages
• Amines in chemical process
solutions
High resolution using the
Dionex IonPac CS19-4μm
column
Improved resolution finds more ions in a single run
9. The Dimension of Scale
9
Parameter Analytical IC Capillary IC
Column diameter 4 mm 0.4 mm
Flow rate 1.0 mL/min 10 μL/min
Injection volume 25 μL 0.4 μL
Eluent consumption 43.2 L/month 0.432 L/month
EGC Lifetime
(@75 mmol/L)
28 days 18 months
EG Current (50 mM KOH) 80.4 mA 0.804 mA
K+ Consumption/Year
26.3 Moles (50 mM
KOH)
0.263 Moles (50
mM KOH)
H2O Consumption/Year 525.6 L 5.25 L
10. The Dimension of Scale – The Concentration Factor
10
Overlay of chromatograms with 4 mm, 2 mm, and 0.4 mm
columns – all with equal injection volume (0.4 μL)
16
-2
1
Sodium
Lithium
Ammonium
Potassium
Magnesium Calcium
16
-2
Sodium
Lithium
Ammonium
Sodium
Potassium
0 2 4 6 8 10 12 14
16
-20
Capillary IC with 0.4 μL injection volume
Conductivity [μS]
Retention time [min]
Microbore IC with 0.4 μL injection volume
Standardbore IC with 0.4 μL injection volume
Potassium
Magnesium Calcium
Lithium
Ammonium
Magnesium Calcium
11. Why Capillary?
• Capillary IC separates ions at mL/min flow rates on 0.4 mm
ID columns with 0.4 μL sample injection
• Lower consumption of eluent (5.2 L water/year)
• Long life time of consumable parts (EGC/18 months)
• Higher mass sensitivity and less sample needed
• Better results and lower cost of ownership
System can be always on and always ready for your samples
11
12. Capillary IC Dionex IC Cube Module and Dual
CD/QD Detectors
12
Guard and Separation Columns
4-Port Injection Valve
Analysis with confidence
Thermo Scientific
Dionex CRD 180
Carbonate Removal
Device
Thermo Scientific™
Dionex™ ACES™ Anion
Capillary Electrolytic
Suppressor
Conductivity Detector
(CD)
Cap IC Degas
Charge Detector (QD)
13. Suppressed Conductivity Detection
13
Time
F -
Cl - SO
2-
4
F - Cl - SO4
2-
Time
μS
μS
Without suppression
With suppression
Eluent (KOH)
Sample F-, Cl-, SO4
2-
Ion-Exchange
Separation Column
Anion Electrolytically
Regenerated
Suppressor
in H2O
KF, KCI, K2SO4
in KOH
Injection valve
Counter ions
HF, HCI, H2SO4
19. Ion Identification and Quantification by CD and QD
A
μA μS
QD
-1 -2
4
19
Column: Dionex IonPac AS11-HC-4μm, 0.4 mm i.d.
Instrument: Dionex ICS-5000+ HPIC system
Eluent Source: Dionex EGC-KOH capillary cartridge
Gradient: 1.52 mM KOH (05 min); 28 mM (58 min),
86 mM (826 min), 1670 mM (2632 min),
70 mM (3238 min)
Flow Rate: 0.0150 mL/min
Inj. Volume: 0.40 μL
Column Temp.: 30 ºC
IC Cube Temp.: 15 ºC
Detection: CD: Suppressed Conductivity Detector
QD: Charge Detector, 6V
Suppressor: Dionex ACES 300 suppressor,
AutoSuppression, recycle mode
Samples A and B are two mixtures each with
three anions
Peak Ret. (Min) Concentration (mg/L)
CD QD Diff. (%)
A (Pass) 1. Acetate 6.08 15.1 15.6 3
2. Chloride 11.86 2.9 2.9 0
3. Tartrate 22.86 12.9 13.2 2
B (Fail) 1. Acetate 6.08 24.0 20.4 15
2. Chloride 11.86 2.9 2.9 0
3. Tartrate 22.86 10.2 11.5 13
Retention time suggests both A and B can be mixtures of
Acetate, Chloride and Tartrate. With <5% acceptance criteria ,
mixture A passes and confirmed as the mixture; mixture B fails.
14
QD
0 5 10 15 20 25
Min
4
-1
CD
B
1
3
1
3
2
14
-2
μA
μS
CD
2
20. Chloride in an Allergy Drug Tablet
9
20
Column: Dionex IonPac AS11-HC-4μm, 0.4 mm i.d.
Instrument: Dionex ICS-5000+ HPIC system
Eluent Source: Dionex EGC-KOH capillary cartridge
Gradient: 1.52 mM KOH (05 min); 2-8 mM (58 min),
816 mM (826 min), 16 70 mM (2632 min),
70 mM (3238 min).
Flow Rate: 0.0150 mL/min
Inj. Volume: 0.40 μL
Column Temp.: 30 °C
IC Cube Temp.: 15 °C
Detection: CD: Suppressed Conductivity Detector
Suppressor: Dionex ACES 300 suppressor,
AutoSuppression, recycle mode
Samples A: One tablet dissolved in 1000 mL water
B: 5-fold dilution of A by water
C: Water blank
Peaks Ret. Concentration
(Min) (mg/L)
A B C
1. Acetate 6.08 0.26 na
2. Chloride 11.86 8.50 1.70 na
3. Nitrite 13.20 0.11 na
4. Nitrate 19.97 0.18 na
5. Carbonate
6. Sulfate 26.01 0.05 na
μS
A
0 10 20 30
Minutes
-1
B
C
2
1 3 4 5 6
21. CD vs. QD Detections for an Allergy Drug Tablet
1 2
21
Column: Dionex IonPac AS11-HC-4μm, 0.4 mm i.d.
Instrument: Dionex ICS-5000+ HPIC system
Eluent Source: Dionex EGC-KOH capillary cartridge
Gradient: 1.52 mM KOH (05 min); 2-8 mM (58 min),
8-16 mM (826 min), 16 70 mM (2632 min),
70 mM (3238 min).
Flow Rate: 0.0150 mL/min
Inj. Volume: 0.40 μL
Column Temp.: 30 °C
IC Cube Temp.: 15 °C
Detection: CD: Suppressed Conductivity Detector
QD: Charge Detector, 6V
Suppressor: Dionex ACES 300 suppressor,
AutoSuppression, recycle mode
Samples One tablet dissolved in 1000 mL water
Peaks Ret. Concentration
(Min) (mg/L)
CD QD
1. Acetate 6.08 0.3 0.4
2. Chloride 11.86 8.5 8.5
3. Nitrite 13.20 0.1
4. Nitrate 19.97 0.2 <LOQ
5. Carbonate (from eluent)
6. Sulfate 26.01 0.1 0.1
7. Unknown 12.70
μS
CD
0 10 20 30
Minutes
0
0
7
6
5
1
QD
3
4
2
22. CD Calibration Curve of Chloride from 0.1 to 500 mg/L
22
0 200 400 600
Chloride (mg/L)
200
Area (μS*min)
0
r2 = 0.9999 %RSD = 2.08
LOQ = 0.004 mg/L
28. Conclusions
• IC is better suited for ionic analytes analysis. IC separates
and directly detects ionic analytes, even without UV
chromophores.
• Using an HPIC system with suppressed conductivity and
charge detectors:
• 22 common pharmaceutical anions were separated in a single analytical
28
run using a Dionex IonPac AS11HC-4μm capillary column
• Multiple counterions in drug products were easily identified and
quantified with confidence
It’s an exciting time to be in Ion Chromatography. The flexibility and versatility of the hardware and the separation tools continues to grow at a phenomenal rate.
Drug development is lengthy and costly process. It screens from about 10,000 compounds down to 1 to 2. It cost billions and take about15 years to develop a new drug. A typical drug development process includes 4 stages, they are drug discovery, pre-clinical, clinical trial, and FDA review. The clinical trial is most expensive in this process. Therefore, all companies do their best identifying the right compound and right formulation before clinical trial. It is essential and most important step.
A high-pressure capillary Ion chromatography system (HPIC) with suppressed conductivity detector (CD) and charge (QD) dual detectors was used.
And Dionex IonPac AS11-HC-4µm is selected for the study.
Many patented technologies included in this system make it a powerful and ease-of-use tool for pharmaceutical application
HPIC +Cap: Always ready
RFIC (EG): Just add water, No mobile phase preparation
Dionex IonPac AS11-HC-4µm capillary column: resolve a large number of inorganic anions and organic acids in a single run using a hydroxide gradient
Dual Detection: Analysis with confidence
UHPLC began the trend toward higher pressures for what reason? People wanted to run faster and save mobile phase.
Remember the Van Deemter Equation?
As the particle size decreases from 8µm to 4µm, column efficiency doubles
This drop in particle size increases the column pressure by 4x
Like HPLC, IC is moving toward smaller particle column technology
HPIC Instrumentation can now handle the pressure of these smaller particle columns, but also higher flow rates.
According to the van Deemter curve, the lower the H value, the higher the separation efficiency. Smaller particle sizes give low H values, ideal for fast separations on short columns.
Third, Dionex IonPac AS11-HC-4µm capillary column was selected for this study because its high-capacity and high-efficiency. This column was specifically designed to resolve a large number of inorganic anions and organic acids in a single run using a hydroxide gradient. It is perfect for analysis of many pharmaceutical interested anions simultaneously.
Remember the Van Deemter Equation?
As the particle size decreases from 8µm to 4µm, column efficiency doubles
This drop in particle size increases the column pressure by 4x
Like HPLC, IC is moving toward smaller particle column technology
HPIC Instrumentation can now handle the pressure of these smaller particle columns, but also higher flow rates.
According to the van Deemter curve, the lower the H value, the higher the separation efficiency. Smaller particle sizes give low H values, ideal for fast separations on short columns.
First, this system is HPIC with High-Pressure Pressure Modules and Capillary IC
The high pressure modules, which includes pump, ATC, EGC, degas modules, allows this all-PEEK flow path HPIC system operated up to 5000 psi. Capillary IC is ion-exchange separations ions at uL/min flow rates on 0.4 mm ID columns. With help of the high pressure modules, scientist can operate ion analysis 24/7 continuously using new 4 µm particle-size capillary columns.
The major advantages of Capillary IC.
IC on Demand:
This is the top customer value. Our customers find a lot of benefits in a true walk-up system, no waiting for equilibration, less calibration and quicker results.
Eluent Generation: Precise and accurate electrolytic inline eluent generation. Just Add Water
Higher mass sensitivity:
The ability to use less sample and still achieve high sensitivity. IC x IC
Lower cost of ownership:
Less eluent, less waste and longer life on EG cartridges.
Keep the system on, it is a always ready system for your samples.
Here is the picture of Dionex IC Cube™ for capillary IC.
The 4th, Dual detections by Suppressed Conductivity(CD) and Charge (QD) Detectors are also important technologies. This series detection help us analysis ions with confidence.
How these two detector works?
The electrolytic suppression technology converts highly conductive hydroxide-based eluents into pure water, reducing the baseline conductivity. While suppressing the eluent, it converts the analytes into their more conductive hydronium (acid) form, enhances their conductance, and increases their sensitivity.
It also eliminates sample carions.
Therefore, it minimizes noise while maximizing sensitivity of conductivity detection.
The Thermo Scientific(TM) Dionex(TM) Charge Detector (QD) is a new detector for ion chromatography. It responds to ionic species by drawing a current at a fixed potential. The Dionex Charge Detector detects ions in proportion to their charge and concentration.
Based on a different technology, the QD detector is an excellent orthogonal detector for the suppressed conductivity (CD) detector.
A high-pressure capillary Ion chromatography system (HPIC) with suppressed conductivity detector (CD) and charge (QD) dual detectors was used.
And Dionex IonPac AS11-HC-4µm is selected for the study.
Many patented technologies included in this system make it a powerful and ease-of-use tool for pharmaceutical application
HPIC +Cap: Always ready
RFIC (EG): Just add water, No mobile phase preparation
Dionex IonPac AS11-HC-4µm capillary column: resolve a large number of inorganic anions and organic acids in a single run using a hydroxide gradient
Dual Detection: Analysis with onfidence
26 most commonly found anions in pharmaceutical were included for this study. They included 23 counter ion and three impurity ions. Many of these ions cannot be analysis by conventional HPLC because they have no UV absorbance and is not retained by HPLC column.
Let’s look at some result,
Here is the chromatogram of 22 anions, which includes most commonly used counter ions and commonly seen impurity ions in pharmaceutical samples. These 22 ions are easily separated using the HPIC system in single run in less than 40 minutes.
With the 26 anions selected, the study shown coelution of 4 pair of ions at this chromatogram condition. Gluconate/Fluoride, Acetate/Glycolate, Succinate/Malate, and Tartrate/Malonate. Data is not shown here.
For each ion, its retention time, conductivity response and charge response are characteristic property for given concentration.
Combining conductivity detector (CD) with charge detector, the ions are identified and confirmed by their characteristic retention time and responses. The calculated sample concentration should agree with each other from CD and QD detector.
With help of QD, it is easy to identify which ion is in the sample.
For example:
The chromatograms from mix sample A and B are shown. They all have three peaks with same retention times. And the peak area are at the similar range of the mix standard just shown.
Based on retention time identification, the peaks could be identified as Acetate, Chloride and Tartrate. Based on a set acceptance criteria of 5% for the variance in the calculated amounts, which can be set by the customer to different levels, A were quantified and confirmed as a mixture of Acetate, Chloride and Tartrate, because the calculated amount of a given peak from CD and QD results were in agreement with each other and met the acceptance criteria requirement of < 5% based on this quantization.
However, sample B showed significant differences in calculated amounts for peak 1 and 3 suggesting either a possible coeluting peak at that location for peak 1 and 3 or possibly a different ionic species.
Acetate/Glycolate
Tartrate/Malonate
Here is a example of counter ion analysis of a allergy drug with counter ion as Chloride. HPIC give excellent result. It not only detect Chloride, but also other counter ions. It give us counter ions profile..
Based on a different technology, CD and QD detectors not only confirm each other, but also they can detect or quantify the ions the other detector can't.
Here is the Chloride calibration curve from CD detection. It is linear over the range 0.1to 500mg/L used in the experiment. The LOQ is 0.004 mg/L.
The result of Chloride from CD is agree with the label 100% for this drug tablet.
Here is another example. It is a Supplement Tablet with counter ion as Tartrate. Compare to allergy tablet, the supplement tablet contains more non reported counter ions.
Tartrate measurement is more challenge than Chloride because it is next to carbonate peak.
Here is chromatogram from CD and QD for undiluted sample.
The tartrate calibration is linear over the range to 50mf/L. The LOQ is 0.06 mg/L. The typical LOQ should be better than Tartrate for other organic acids.
The result shows that detected Tartrate less than the label value. It is not surprised because there are significant amount of Acetate, Formate, Chloride, Nitrite, and Nitrate in the tablet.