<h3>Too much interfering matrix? Discover how to streamline your daily LC-MS analysis with turbulent flow chromatography.</h3>Sample preparation is a critical step in liquid chromatography-mass spectrometry (LC-MS) analysis to achieve quantitative accuracy and precision. Directly injecting crude samples into your instrument without prior cleanup to remove interfering compounds can clog the flow path, damage your detector, and negatively impact your analyses through a “matrix effect.”<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Automated_LC_MS_Sample_Cleanup_Using_Turbulent_Flow_Chromatography_c7647c2c50.jpg" alt="Thermo Fisher Scientific: Automated LC-MS Sample Cleanup Using Turbulent Flow Chromatography." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Automated_LC_MS_Sample_Cleanup_Using_Turbulent_Flow_Chromatography_c7647c2c50.jpg 245w," sizes="100vw" width="1024" height="512">Common approaches to clean up samples and suppress the matrix effect include simple dilution and centrifugation to extensive extraction techniques. The common scope of all these procedures is to minimize the possible contamination of your LC-MS system but, more importantly, to reduce to a minimum the interference of unrelated sample components on the detection and quantification of your analytes of interest.A point to note is the preparation method you choose often depends on the complexity of your sample. For instance, samples for clinical research applications or toxicology tend to have high levels of interfering matrix and require a more sophisticated clean-up approach.&nbsp; Let’s dive into what a matrix effect is, the impacts on your LC-MS data, and an effective method called turbulent flow chromatography you can use to clean complex samples.1<h3 id="h-what-exactly-is-matrix-effect">What exactly is matrix effect?</h3>Any chemical entity in your sample capable of coeluting or interacting with analytes of interest can generate matrix effect, ultimately impacting the integrity of your data.Interfering matrix compounds come from endogenous and exogenous sources, but biological samples like blood or serum, and food and environmental extracts inherently have higher levels of interfering compounds.Some examples of interfering matrix compounds include ion-suppressing salts, proteins, lipids, compounds capable of ion-pairing interactions, and polymers.<h3 id="h-how-does-matrix-effect-impact-your-lc-ms-data">How does matrix effect impact your LC-MS data?</h3>Because matrix compounds interfere with the detection and quantitation of your target analytes, the effects ultimately lead to an under- or overestimation in analyte quantification.In the case of LC-MS, the matrix effect triggers ion suppression2, which happens when compounds from the sample matrix inhibit charge transfer from the ion source to your target analytes – a prime example is electrospray ionization, where the detection relies on efficient charge transfer to analytes.Analytes and matrix components will naturally compete for the available charge from the MS ion source. And when compounds of your sample matrix are present in higher concentrations than your analytes, these unwanted molecules can capture more of the charge, leaving fewer ions available for charge transfer to your analytes.Hence suppression of charge transfer to your analytes leads to poor accuracy and limits of detection and quantitation.<h3 id="h-sample-preparation-methods-to-remove-interfering-matrix">Sample preparation methods to remove interfering matrix</h3>Using the example of ion suppression, you can see how eliminating the competition for charge transfer between matrix components and analytes through proper sample cleaning is essential to developing a method with quantitative accuracy.Solid-Phase Extraction (SPE) and Liquid-Liquid Extraction (LLE) are techniques used to clean samples before LC-MS analysis. 3,4<ul><li>In SPE, a liquid sample is loaded onto a column packed with a solid adsorbent material. The analytes of interest are retained on the adsorbent material while unwanted matrix components are washed away. The retained analytes are then eluted using a solvent. This approach is typically developed on a specific panel of target analytes.</li><li>LLE is based on the differential solubility of analytes between two immiscible solvents; once a partition equilibrium is reached, the enriched solvent is separated and, usually, evaporated to dryness and reconstituted in a solvent compatible with LC-MS.</li></ul>Regardless of the <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/chromatography/chromatography-learning-center/chromatography-consumables/sample-prep.html">sample preparation</a> approach you decide to use, these manual procedures are imprecise, time-consuming, and labor-intensive—even a quick and easy cleanup is subject to human errors like improper pipetting or sample mix-up.<h3 id="h-automated-online-sample-cleanup-for-efficient-sample-preparations">Automated online sample cleanup for efficient sample preparations</h3>To overcome the bottlenecks and risks of manual approaches, automated sample cleanup is gaining popularity, thanks to much less human intervention combined with better speed and analytical reproducibility.Online SPE&nbsp;is an improvement over manual ones, where the extraction process integrates directly with your LC system. The sample is automatically injected onto an extraction cartridge, cleanup occurs, and your extracted sample transfers directly to the MS instrument (flow injection analysis) or to an analytical column for further separation and detection.Turbulent flow chromatography (TurboFlow) is a more advanced online sample cleanup approach combining the aspects of the chemical affinity of SPE with size exclusion chromatography (SEC).5<h3 id="h-how-does-turbulent-flow-chromatography-work">How does turbulent flow chromatography work?</h3>TurboFlow separates low molecular weight molecules from high molecular weight matrix components using a specialized sample extraction column on LC systems (Figure 2).Here’s a detailed look at how TurboFlow works:<ol><li>Your sample is directly injected into a <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/order/catalog/product/CH-952434">TurboFlow column</a> (typically large &gt; 50 µm particle size with macropores).</li><li>The sample flows through the column at high linear velocities, creating turbulence to enhance the interaction between the sample components and the stationary phase.</li><li>Low molecular weight molecules diffuse into the pores faster than high molecular weight components and quickly flush to waste. Only the small molecules with an affinity for the particle chemistry bind to the internal pore surfaces.</li><li>A change in mobile phase composition elutes the small molecules bound by the TurboFlow column for further separation and detection.</li></ol><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Automated_LC_MS_Sample_Cleanup_Using_Turbulent_Flow_Chromatography_3_a261253a52.jpeg" alt="Thermo Fisher Scientific: Figure 1. Illustration showing how turbulent flow chromatography works." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Automated_LC_MS_Sample_Cleanup_Using_Turbulent_Flow_Chromatography_3_a261253a52.jpeg 245w," sizes="100vw" width="1024" height="512"><h3 id="h-benefits-of-turbulent-flow-chromatography-for-sample-preparation-over-spe">Benefits of turbulent flow chromatography for sample preparation over SPE</h3>While both TurboFlow and online SPE streamline and automate the sample preparation process, TurboFlow has key differences and advantages to consider (Figure 2).<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Automated_LC_MS_Sample_Cleanup_Using_Turbulent_Flow_Chromatography_4_221b9dda9b.jpg" alt="Thermo Fisher Scientific: Figure 2. TurboFlow vs. SPE for sample cleanup." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Automated_LC_MS_Sample_Cleanup_Using_Turbulent_Flow_Chromatography_4_221b9dda9b.jpg 245w," sizes="100vw" width="700" height="410"><ol><li>TurboFlow provides a cleaner sample compared to SPE<ul><li>The more efficient dual mode of action (chemical affinity plus SEC)</li><li>The elution performed by a strong solvent plug potentially reduces the transfer of residual matrix components to your MS</li></ul></li><li>A cleaner sample means<ul><li>Reduced ion suppression, leading to increased sensitivity</li><li>Less mass spectrometer contamination</li><li>Extended analytical column lifespan</li><li>Faster analytical gradients</li></ul></li></ol>Moreover, the opportunity to modulate the strength of the mobile phase reaching the analytical column allows for better analyte focusing on the head of the column, significantly improving your chromatography.<h3 id="h-streamline-your-daily-lc-ms-analysis-with-turboflow-technology">Streamline your daily LC-MS analysis with TurboFlow technology</h3><div style="grid-template-columns:auto 60%;"><div>Automated sample cleanup using <a target="_blank" rel="noreferrer noopener" aria-label="online TurboFlow technology - open in a new tab" data-uw-rm-ext-link="" uw-rm-external-link-id="https://assets.thermofisher.com/tfs-assets/cmd/brochures/br-74120-lc-ms-transcend-uhplc-systems-br74120-en.pdf$onlineturboflowtechnology"><a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/brochures/br-74120-lc-ms-transcend-uhplc-systems-br74120-en.pdf">online TurboFlow technology</a></a> is a rapid and efficient sample preparation approach that considerably improves method accuracy, reliability, and sensitivity. Adopting this technology can even enhance the competitiveness of your laboratory by allowing faster results, lower costs per sample, and improved reproducibility and MS sensitivity.<figure class="image"><img style="aspect-ratio:700/410;" src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Automated_LC_MS_Sample_Cleanup_Using_Turbulent_Flow_Chromatography_2_0a20492c6a.jpg" alt="Thermo Fisher Scientific: Figure 3. Transcend TLX TurboFlow UHPLC System." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Automated_LC_MS_Sample_Cleanup_Using_Turbulent_Flow_Chromatography_2_0a20492c6a.jpg 245w," sizes="100vw" width="700" height="410"></figure><blockquote><a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/chromatography/liquid-chromatography-lc/hplc-uhplc-systems/transcend-turboflow-tlx-systems.html">Learn how TurboFlow can ease your lab’s daily LC-MS analysis of complex matrices today</a>.</blockquote><article aria-label="Automated LC-MS Sample Cleanup Using Turbulent Flow Chromatography"><div><blockquote>Visit us on <a target="_blank" rel="noreferrer noopener" aria-label="LinkedIn: - open in a new tab" data-uw-rm-ext-link="" uw-rm-external-link-id="https://www.linkedin.com/showcase/72003132/admin/dashboard/$linkedin:"><a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a></a> #TurbulentflowChromatography #lcms #IonSuppression</blockquote></div></article><section><blockquote><h4>Dan Kalu Appulage</h4>Dr. Dan Kalu Appulage is a Product Management Specialist in the HPCS business unit at Thermo Fisher Scientific. He holds a Ph.D. in Analytical Chemistry, an M.A., and B.S. in Chemistry. His professional background includes expertise in product management, LCMS method development, and teaching. Dan is passionate about education and loves sharing his knowledge and experiences with others. Outside of work, Dan enjoys playing volleyball and traveling with his family.</blockquote></section></div></div>

Automated LC-MS Sample Cleanup Using Turbulent Flow Chromatography

<h3>Part 4: Going beyond 4D to improve analytical performance for targeted quantitative analysis</h3>This is the fourth in a multi-part blog series highlighting the key attributes and impressive benefits of the Thermo Scientific Stellar mass spectrometer—the first-of-its-kind instrument designed and optimized for highly multiplexed targeted quantitation, ideally suited for discovery verification. By delivering robust analytical methods and dramatically improved turnaround time, this solution helps labs boost capacity and differentiate themselves to generate more revenue. For additional background, see blog <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5077">Part 1</a>, <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5086">Part 2 </a>and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5416">Part 3</a> here and stay tuned for more blogs on our website.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Why_You_Need_a_Verification_Class_Mass_Spectrometer_Going_Beyond_4d_to_Improve_Analytical_Performance_for_Targeted_Quantitative_Analysis_125258804e.jpg" alt="Thermo Fisher Scientific: Why You Need a Verification-Class Mass Spectrometer: Going Beyond 4d to Improve Analytical Performance for Targeted Quantitative Analysis." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Why_You_Need_a_Verification_Class_Mass_Spectrometer_Going_Beyond_4d_to_Improve_Analytical_Performance_for_Targeted_Quantitative_Analysis_125258804e.jpg 245w," sizes="100vw" width="1200" height="600">Analytical specificity is one of the most critical requirements for successful targeted quantitative analysis. Assigning measured data to diagnostic product ions from the analyte of interest increases the confidence in resulting measurement determining the analyte expression level, copy number, or absolute amount in each sample, as well as across an entire study. Using empirically determined values for liquid chromatography (LC) and mass spectrometry (MS) provides specific information that collectively increases data processing. This orthogonal information comes in the form of 1) chromatographic retention times and peak shapes; 2) precursor m/z value; 3) MS/MS product ions; and 4) MS/MS product ion distribution profiles, which can be stored to form spectral libraries that are used to not only process LC-MSn data but build confident targeted data acquisition methods.<h3>4D parameter determination: Sufficient or not?</h3>Previous publications touted utilization of four-dimensional (4D) parameter determination to confidently create and process untargeted and targeted data. Using LC coupled to a trapped ion mobility QTOF (timsTOF) mass spectrometer, each analyte is annotated by four empirical measurements across all study samples: 1) measured retention time; 2) ion mobility as measured by its collision cross section (CCS); 3) precursor m/z value; and 4) presence of corresponding product ions. The assumption is that the orthogonal selectivity achieved by UHPLC separation and ion mobility resolution relative to the precursor isolation is sufficient to differentiate a specific analyte from co-eluting isobaric and isomeric ions and that resulting product ions are only attributed to the isolated precursor. <a target="_blank" rel="noopener noreferrer" href="https://arxiv.org/pdf/2111.03134">Adding CCS values can help accommodate for some variability</a> but requires more work by the researcher to accurately determine the variance associated with ion mobility. <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/1885960_lcms_179_lipidomics_short_gradient_ebook_rev_01_ed630faf92/1885960-lcms-179-lipidomics-short-gradient-ebook-rev-01.pdf">At no point are the product ion ratios used as an additional dimension for verification</a>.A smart addition: product ion ratio determination Product ion ratio determination, however, has been used as the gold standard for qualitative data analysis for SRM/MRM acquisition for decades. Despite quantitative methods on triple quadrupole mass spectrometers acquiring data for only two or three product ion transitions, the inclusion of the resulting product ion ratio is used to qualitatively verify that the signal measured per SRM transition is attributed to the analyte of interest. This concept has been included in the targeted quantitative studies performed using the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Thermo Scientific Stellar mass spectrometer (MS)</a>, significantly increasing analytical performance for a wide range of molecules.To increase the quantitative selectivity and specificity needed for confident data acquisition, the proposed solution combines the chromatographic separation capabilities of the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=40&amp;search=vanquish">Thermo Scientific Vanquish UHPLC system </a>with the innovative PRM acquisition on the Stellar mass spectrometer to go beyond data processing confidence.&nbsp; Additionally, the proposed method leverages intelligent data acquisition to perform RT alignment reducing the need to apply additional post-acquisition data processing steps.&nbsp; This blog covers the differentiation for each of these steps while presenting an important 5th dimension—extending PRM data analysis to the MS3 level.<h3>Dimension #1: Leveraging 1,500 bar UHPLC separation to drive orthogonal selectivity</h3>Using the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/398">Thermo Scientific Vanquish Neo</a> and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/744">Horizon UHPLC</a> systems, researchers can harness higher backpressure capabilities covering a wide range of flow rates from nanoflow to analytical flow rates—increasing peak capacity while driving higher utilization rates than HPLC systems with only 1,000 bar of backpressure. T<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=40&amp;search=vanquish">he Vanquish UHPLC systems</a> also deliver reproducible performance over the course of longer studies such as populational health.Going beyond the first dimension: Including the Adaptive RT routine enables LC mapping to assign true retention time values to each analyte with narrower retention time windows. The Adaptive RT routine works for small and large molecules, from single-cell to bulk analysis, and bridges method development between longer discovery gradients and faster targeted quantitation gradients without the need for spiked RT standards.&nbsp; The advantage is that the retention time alignment for the study is reliably performed during data acquisition, not processing.<h3>Dimension #2: Introduction of targeted analytes</h3>Following UHPLC separation and ionization, targeted analytes (precursors) are introduced into the MS and moved through the ion flight path to the detector. The quadrupole mass filter (termed isolating quadrupole or Q1) has an RF/DC offset to transmit a narrow m/z range centered on the target precursor m/z value. The mass range used for precursor ion filtering is ca. 1 to 2 Th depending on the mass spectrometer. Leveraging precursor isolation following chromatographic separation increases the target analyte selectivity relative to co-eluting compounds.Going beyond the second dimension: The Stellar mass spectrometer’s QR5 Plus quadrupole mass filter uses hyperbolic-surfaced quadrupole rods that improve ion transmission efficiency across a wider precursor m/z range. Unit resolution settings are 0.7 Th at the baseline—significantly better than other quadrupole mass spectrometers using 1.2 to 2 Th (almost 2-3x wider), which can compromise quantitative performance.<h3>Dimension #3: Acquiring PRM data from more product ions</h3>The<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149"> Stellar mass spectrometer </a>acquires PRM data which is comprised of full scan MS2 spectra per scan event relative to SRM/MRM acquisition. Acquiring data for many more product ions per unit time increases the specificity of the resulting measurement. It also enables post-acquisition data processing methods to determine specific product ions used for quantitation without having to update the experimental method and re-analyze samples.Going beyond the third dimension:&nbsp; The Stellar mass spectrometer combines the unique capabilities of dual ion packet management with ion accumulation outside of the ion trap to boost quantitative performance.&nbsp; Simultaneously managing two different ion packets enables longer accumulation times without significantly compromising the PRM acquisition rates which becomes imperative when performing quantitative measurements at the LOD and LOQ levels.<h3>Dimension #4: Leveraging the full scan MS2 spectrum and multiple product ions to evaluate the product ion ratios compared to a reference spectrum</h3>As mentioned above, ion ratio calculations are used in validated quantitative methods to ensure selectivity relative to the matrix or background interference per product ion.Going beyond the fourth dimension: What, where and how you perform ion accumulation differentiates the effectiveness of each mass spectrometer. The Stellar MS first filters for the targeted precursor m/z value, then accumulates product ions in an ion-routing multipole (as has been done on Thermo Scientific Orbitrap mass spectrometers for over a decade).&nbsp; Performing tandem MS in this order maximizes sensitivity for low-level product ions to maintain accurate ion ratio analysis. Finally, incorporating dynamic AGC automates the accumulation time regardless of precursor ion flux. (Reference: <a target="_blank" rel="noopener noreferrer" href="https://doi.org/10.1101/2024.06.04.597431">Plubell et al. BioRxiv</a>)<h3>Dimension #5: Addressing sensitivity disrupters</h3>Targeted quantitation for specific analytes using MS2 acquisition may have co-eluting isomeric/isobaric ions potentially disrupting quantitative sensitivity (signal-to-noise limitation).&nbsp; Two options to pursue would be modifying LC gradients or increasing the tandem MS level to MS3. Elongating the LC gradient decreases sample throughput yet still may not remove all background interferences. The Stellar MS, on the other hand, can implement MS3 acquisition with exceptionally fast acquisition speeds (up to 40 Hz) to maintain target capacity and the number of data points per LC peak.Going beyond the fifth dimension:&nbsp;In addition to the unique MS3 acquisition speed, the Stellar MS implements dynamic AGC to maximize spectral quality across a wider dynamic range, as well as the ability to perform either HCD or CID at each MSn level. Finally, introduction of Adaptive RT to confidently manage scheduled retention time windows ensures tMS3 methods can succeed for increased target capacity using faster LC gradients.<blockquote>For more information, explore the <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/mass-spectrometry/liquid-chromatography-mass-spectrometry-lc-ms/lc-ms-systems/orbitrap-lc-ms/stellar-mass-spectrometer.html">Stellar mass spectrometer</a> and <a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/brochures/eb-003672-lsms-stellar-2024-year-in-review-eb003672-na-en.pdf">download our new 2024 year in review ebook</a>.Visit us on <a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a> #StellarMassSpectrometer #Vanquish #UHPLC</blockquote><section><blockquote><h5>Dr. Scott Peterman</h5><div>Scott Peterman, Ph.D., is Senior Product Marketing Manager for Life Science Mass Spectrometry of the Chromatography and Mass Spectrometry Division of Thermo Fisher Scientific.</div></blockquote></section>

Why You Need a Verification-Class Mass Spectrometer: Going Beyond 4d to Improve Analytical Performance for Targeted Quantitative Analysis

<h3>Smarter sample preparation for LC-MS: from simplicity to selectivity</h3>In any toxicology lab, sample preparation is more than a preliminary step—it’s the foundation for accuracy, reproducibility, and workflow efficiency. In a recent <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/webinar/3978">webinar</a>, we explored a range of sample preparation strategies—from minimal processing to highly selective techniques—with additional insights shared by Dr. William Clarke, PhD, MBA, DABCC, Professor of Pathology and Deputy Director of Quality and Regulatory Affairs at Johns Hopkins University School of Medicine. These discussions build on our latest white paper, “<a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/Reference-Materials/wp-000861-lsms-clinical-tox-explorer-toxicology-wp000861-na-en.pdf">Context matters: selecting LC-MS sample preparation methods for LC-MS/MS in clinical research and toxicology applications</a>“, authored by Prof. Alain Verstraete (University Hospital Ghent). The paper highlights commonly used LC-MS sample preparation methods and provides practical guidance to help laboratories select the most appropriate approach for their needs.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Sample_Preparation_Strategies_Demystified_Choosing_the_Right_Fit_for_Your_Toxicology_Workflow_5_722a357221.jpg" alt="Thermo Fisher Scientific: Sample Preparation Strategies Demystified: Choosing the Right Fit for Your Toxicology Workflow: Thermo Scientific SOLAμ SPE Plates—Explore SOLA." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Sample_Preparation_Strategies_Demystified_Choosing_the_Right_Fit_for_Your_Toxicology_Workflow_5_722a357221.jpg 245w," sizes="100vw" width="700" height="340"><h3>The power of simplicity: dilute-and-shoot and protein precipitation</h3>For relatively clean matrices like urine, a dilute-and-shoot approach can be effective. This method involves minimal handling and is low-cost but generally best suited for low-protein samples to avoid ion suppression or instrument issues. For samples rich in proteins, such as plasma, serum, or whole blood, protein precipitation (PPT) is a common and straightforward method. It uses organic solvents—often methanol—to denature and precipitate proteins. After incubation at low temperatures and centrifugation, the supernatant is collected and may be further diluted. Additives like zinc sulfate can be added to enhance protein precipitation or aid cell lysis. While PPT is less selective, it effectively reduces matrix complexity and is compatible with <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/forensics/forensic-toxicology/tox-explorer-collection-lc-ms.html">robust LC-MS instrumentation</a>. As a plug-and-play approach, the <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/forensics/forensic-toxicology/tox-explorer-collection-lc-ms.html">Thermo Scientific Tox Explorer</a> method, with over 2,000 compounds in its library, includes sample preparation recommendations for varying matrices, including dilute-and-shoot and protein precipitation.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Sample_Preparation_Strategies_Demystified_Choosing_the_Right_Fit_for_Your_Toxicology_Workflow_4_658266d072.jpg" alt="Thermo Fisher Scientific: Sample Preparation Strategies Demystified: Choosing the Right Fit for Your Toxicology Workflow: Tox Explorer compound library shown in mzVault." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Sample_Preparation_Strategies_Demystified_Choosing_the_Right_Fit_for_Your_Toxicology_Workflow_4_658266d072.jpg 245w," sizes="100vw" width="1024" height="480">Enhancing selectivity: Phospholipid Removal, Liquid-Liquid Extraction (LLE), Supported Liquid Extraction (SLE), and Solid-Phase Extraction (SPE)When higher selectivity and sensitivity are required, extraction-based methods are employed:<ul><li>Phospholipid Removal uses commercial solutions to reduce matrix components that can cause ion suppression. Though relatively simple, it requires some specialized materials and does not concentrate analytes.</li><li>Liquid-Liquid Extraction (LLE) separates analytes based on their solubility differences between aqueous biological fluids and immiscible organic solvents. This technique removes many matrix interferences but is labor-intensive and challenging to automate.</li><li>Supported Liquid Extraction (SLE)&nbsp;improves upon LLE by using a porous support to retain the aqueous phase, allowing nonpolar analytes to partition into an organic solvent, which can be collected more efficiently as flow-through. SLE offers cleaner extracts and better reproducibility, making it more compatible with higher-throughput workflows.</li><li>Solid-Phase Extraction (SPE) selectively retains analytes on sorbent phases based on chemical characteristics such as polarity or charge. Impurities are washed away, and analytes are eluted with strong organic solvents, often followed by drying and reconstitution. SPE improves consistency and reduces matrix effects, especially in complex samples or high-throughput environments. Various sorbents, including ion exchange types, can be selected, or even combined, depending on analyte chemistry.</li></ul><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Sample_Preparation_Strategies_Demystified_Choosing_the_Right_Fit_for_Your_Toxicology_Workflow_2_fee3c7bdd8.jpg" alt="Thermo Fisher Scientific: Sample Preparation Strategies Demystified: Choosing the Right Fit for Your Toxicology Workflow: Common sample preparation methods for LC-MS featured in table 1 of white paper 000861." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Sample_Preparation_Strategies_Demystified_Choosing_the_Right_Fit_for_Your_Toxicology_Workflow_2_fee3c7bdd8.jpg 245w," sizes="100vw" width="1000" height="548"><h3>Unlocking efficiency: how automation is transforming sample preparation</h3>As labs face staffing shortages and increasing sample volumes, automation is becoming essential. Solutions from providers like Hamilton and Tecan help streamline sample preparation tasks, including pipetting, plate transfers, and offline SPE. This can dramatically reduce hands-on time and standardize processes. In the webinar, Dr. Clarke shares that one lab, for example, was able to cut total sample preparation time in half—from six hours to three—and reduce hands-on analyst time from three hours to just 10 minutes by using a Tecan platform with SPE plates. Each of the extraction methods discussed can be readily programmed onto these liquid handling robots. Still, automation brings new challenges—like programming robots, accounting for sample variability, managing liquid classes (e.g., whole blood vs. serum), and replicating the precision of skilled human pipetting, which remains difficult to fully automate and underscores the continued importance of human expertise<h3>Emerging trends: dried blood spots and microsampling</h3>Dried blood spots (DBS) and microsampling techniques promise minimally invasive collection and improved sample logistics. Fixed-volume devices with or without pre-punched filter cards can simplify automation and downstream analysis. However, challenges remain: hematocrit effects, uneven sample spread, storage issues, and potential for contamination or hemolysis.Capillary sampling from fingersticks may seem like a step toward decentralized testing, but it’s not without challenges—sample quality can be affected by peripheral blood differences or inconsistent collection techniques.To address some of these limitations, particularly the need for extensive sample prep for screening purposes, direct analysis methods are gaining traction. The <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/mass-spectrometry/liquid-chromatography-mass-spectrometry-lc-ms/lc-ms-accessories/verispray-paperspray-ion-source-mass-spectrometry.html">Thermo Scientific VeriSpray PaperSpray ion source</a> offers a direct MS-based ionization approach for analyzing dried samples, eliminating the need for time-consuming sample preparation and chromatographic separation. This can be especially useful for complex matrices like whole blood, which often require more intensive extraction to remove proteins.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Sample_Preparation_Strategies_Demystified_Choosing_the_Right_Fit_for_Your_Toxicology_Workflow_3_cb6f7e0282.jpg" alt="Thermo Fisher Scientific: Sample Preparation Strategies Demystified: Choosing the Right Fit for Your Toxicology Workflow: VeriSpray paper spray ionization is a rapid and user-friendly sample introduction technique that delivers samples directly to the mass spectrometer using electrospray ionization. The process is straightforward—just add the sample and solvent to the paper." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Sample_Preparation_Strategies_Demystified_Choosing_the_Right_Fit_for_Your_Toxicology_Workflow_3_cb6f7e0282.jpg 245w," sizes="100vw" width="1024" height="271"><h3>Final takeaway: clean samples, better results</h3>The overarching message: cleaner samples drive better assay performance. Whether you’re processing high-throughput toxicology screens or quantifying small molecules and peptides, aligning your sample preparation strategy with both analytical and operational goals is essential. From simple dilute-and-shoot methods to advanced approaches or fully automated workflows, thoughtful preparation can enhance instrument uptime, improve assay accuracy, and reduce long-term operational costs. A recent technical note—linked under the SPE section in the supporting documents below—demonstrates this effectively using a large urine drug panel. Solid-phase extraction plates improved both assay robustness and accuracy. By extracting just 200 µL of sample and minimizing solvent use, the workflow successfully reduced reagent costs and waste without sacrificing data quality. As mass spectrometry continues to expand into more complex and decentralized applications, laboratories that invest in fit-for-purpose sample prep strategies will be best positioned to deliver confident, high-quality results at scale. To support these efforts, Thermo Fisher Scientific offers a variety of aligned resources, including those discussed in the webinar and this blog:<ul><li>Dilute-and-shoot: See the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/tn_000794_lsms_tox_explorer_orbitrap_exploris_120_drugs_of_abuse_tn000794_na_en_3286411f97/tn-000794-lsms-tox-explorer-orbitrap-exploris-120-drugs-of-abuse-tn000794-na-en.pdf">Thermo Scientific Tox Explorer method for Orbitrap-based screening of 120 drugs of abuse</a> and <a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/Reference-Materials/wp-000861-lsms-clinical-tox-explorer-toxicology-wp000861-na-en.pdf">this white paper highlighting the comparison of sample prep methods.</a></li><li>Protein Precipitation: <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/tn_73168_lc_ms_drugs_of_abuse_tn73168_en_6ff028434e/tn-73168-lc-ms-drugs-of-abuse-tn73168-en.pdf">Quantification of 78 drugs of abuse in human blood by liquid chromatography – HRAM Orbitrap mass spectrometry for clinical research</a>.</li><li>Solid phase extraction (SPE): Learn more through our tox drugs of abuse <a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/Technical-Notes/tn-002363-clinical-lc-ms-homestead-tn002363-na-en.pdf">Thermo Scientific Orbitrap Exploris 120 MS</a> and <a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/Technical-Notes/tn-002606-lsms-clinical-toxicology-doa-tn002606-na-en.pdf">Thermo Scientific TSQ Quantis Plus MS method for clinical toxicology</a> technical notes.</li><li>Automation: See how oral fluid extraction is streamlined using automation in <a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/Technical-Notes/tn-003851-cl-lcms-stellar-oral-fluid-tn003851-na-en.pdf">this technical note featuring Thermo Scientific Stellar MS.</a></li><li>Dried sample workflows: Explore simplified prep using the Thermo Scientific VeriSpray PaperSpray Ion Source in <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/tn_73467_ps_ms_paperspray_tandem_ms_drugs_of_abuse_urine_tn73467_en_d81464d205/tn-73467-ps-ms-paperspray-tandem-ms-drugs-of-abuse-urine-tn73467-en.pdf">this technical note on urine drug analysis.</a></li></ul><blockquote>Visit us on&nbsp;<a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a>&nbsp;#SamplePreparation, #ForensicToxicology, #toxicology, #lcms</blockquote><blockquote><h4>Ema Ruzic</h4>Vertical Marketing Manager, Chromatography and Mass Spectrometry Division (CMD)</blockquote>

Sample Preparation Strategies Demystified: Choosing the Right Fit for Your Toxicology Workflow

Welcome back to our series on <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/cz/en/home/industrial/chromatography/chromatography-learning-center/liquid-chromatography-information/hplc-system-components/how-hplc-detectors-work/charged-aerosol-detection.html?erpType=Global_E1">Charged Aerosol Detection (CAD) in High-Performance Liquid Chromatography (HPLC).</a> In the first two episodes, we explored the fundamentals and benefits of CAD and compared it to other universal detectors like ELSD and MALS.&nbsp;<blockquote><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5390">Episode 1: The Benefits of Charged Aerosol Detection (CAD) in High-Performance Liquid Chromatography (HPLC)</a><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/6250">Episode 2: The Benefits of CAD Compared to Other Universal Detectors: ELSD and MALS</a></blockquote>In this episode, we will delve deeper into the inner workings of CAD, providing a detailed understanding of its operation and the technology behind it.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Understanding_How_Charged_Aerosol_Detection_CAD_Works_7e2b6c4dd6.jpg" alt="Thermo Fisher Scientific: Understanding How Charged Aerosol Detection (CAD) Works" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Understanding_How_Charged_Aerosol_Detection_CAD_Works_7e2b6c4dd6.jpg 245w," sizes="100vw" width="1200" height="600"><h3>The basics of CAD</h3>Charged Aerosol Detection (CAD) is a universal detection method used in HPLC that provides a consistent response for non-volatile and semi-volatile analytes. CAD operates by converting the liquid eluent from the HPLC column into charged aerosol particles, which are then detected to generate a signal proportional to the mass of the analyte. Let’s break down the process step by step.<h3>Step-by-step operation of CAD</h3><h4>1. Nebulization</h4>The first step in CAD is the nebulization of the liquid eluent from the HPLC column. The eluent is introduced into a nebulizer, where it is transformed into a fine aerosol. This is achieved by using a high-velocity gas stream (usually nitrogen) that shears the liquid into tiny droplets. The size of these droplets is typically in the micron range.<h5>Key components:</h5><ul><li>Nebulizer: Converts the liquid eluent into an aerosol.</li><li>Gas stream: Typically nitrogen, used to create the aerosol droplets.</li></ul>Detailed process: The liquid eluent enters the nebulizer, where it meets a high-velocity gas stream. This interaction causes the liquid to break up into small droplets, forming an aerosol. The efficiency of nebulization is crucial, as it determines the size and uniformity of the droplets, which can affect subsequent steps in the detection process.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Understanding_How_Charged_Aerosol_Detection_CAD_Works_3_74ffbd69fa.jpg" alt="Thermo Fisher Scientific: Understanding How Charged Aerosol Detection (CAD) Works" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Understanding_How_Charged_Aerosol_Detection_CAD_Works_3_74ffbd69fa.jpg 245w," sizes="100vw" width="1160" height="600"><h4>2. Evaporation</h4>After nebulization, the aerosol droplets enter a heated drift tube. In this tube, the solvent evaporates, leaving behind dried analyte particles. The temperature of the drift tube is carefully controlled to ensure complete evaporation of the solvent without decomposing the analyte.<h5>Key components:</h5><ul><li>Heated drift tube: Evaporates the solvent, leaving dried analyte particles.</li></ul>Detailed process: The aerosol droplets pass through the heated drift tube, where they are subjected to a controlled temperature. The solvent in the droplets evaporates, resulting in the formation of dried particles that contain the analyte. The drift tube’s temperature must be optimized to prevent the degradation of thermally sensitive analytes while ensuring complete solvent removal.<h4>3. Charging</h4>The dried analyte particles then pass through a corona discharge, where they are exposed to a high-voltage electrical field. This field imparts a charge to the particles. The corona discharge generates ions that attach to the analyte particles, effectively charging them.<h5>Key Components:</h5><ul><li>Corona discharge: Generates ions to charge the analyte particles.</li></ul>Detailed process: As the dried particles exit the drift tube, they enter the corona discharge region. Here, a high-voltage electrode ionizes the surrounding gas, creating a corona discharge. The ions generated in this discharge attach to the analyte particles, imparting a charge to them. This charging process is critical, as the strength of the signal detected later is proportional to the charge on the particles.<h4>4. Detection</h4>The charged particles are then directed into a detector, typically an electrometer, which measures the quantity of charge. The signal produced by the electrometer is proportional to the amount of analyte present. This signal is then processed and displayed as a chromatogram, showing the concentration of the analyte over time.<h5>Key components:</h5><ul><li>Electrometer: Measures the charge on the analyte particles.</li><li>Data processor: Converts the measured charge into a readable signal.</li></ul>Detailed process: The charged particles flow into the electrometer, where the charge is measured. The electrometer converts the charge into an electrical signal, which is proportional to the quantity of analyte. This signal is then processed by data analysis software, which generates a chromatogram. The peaks in the chromatogram correspond to the concentration of the analyte at different time points, allowing for quantitative analysis.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Understanding_How_Charged_Aerosol_Detection_CAD_Works_2_363e6af2fa.jpg" alt="Thermo Fisher Scientific: Understanding How Charged Aerosol Detection (CAD) Works" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Understanding_How_Charged_Aerosol_Detection_CAD_Works_2_363e6af2fa.jpg 245w," sizes="100vw" width="960" height="540">You can find more information on why to choose <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/cz/en/home/industrial/chromatography/chromatography-learning-center/liquid-chromatography-information/hplc-system-components/how-hplc-detectors-work/charged-aerosol-detection.html">Charged Aerosol Detection for your HPLC analysis</a><h3>Conclusion</h3>Charged Aerosol Detection (CAD) is a powerful and versatile detection method in HPLC, offering consistent response, high sensitivity, robustness, and ease of use. By understanding the step-by-step operation of CAD, we can appreciate the technology’s ability to provide reliable and accurate detection across a wide range of analytes.As we continue our series on CAD, stay tuned for the next episode, where we will explore specific case studies and practical applications of CAD in various industries, demonstrating its real-world impact and benefits.Thank you for joining us in this deep dive into the workings of Charged Aerosol Detection. We hope this episode has provided you with a clearer understanding of CAD and its advantages in analytical chemistry.<blockquote>Visit us on LinkedIn: #CAD, #ChargedAerosolDetection #HPLCAuthor: Marcus KleeMarcus Klee is the Regional Marketing Manager for HPLC in EMEA at Thermo Fisher Scientific. He holds a Dipl.-Ing. in Chemical Engineering and has extensive experience in marketing, sales, and communications within the chemical and physical technology sectors.</blockquote>

Episode 3: Understanding How Charged Aerosol Detection (CAD) Works

Mineral oil hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH) have moved from niche laboratory concerns to central topics in food safety, regulatory policy, and analytical science.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_MOSH_MOAH_Analysis_Technology_Regulation_and_the_Road_Ahead_2_f79d1ed4ee.jpg" alt="Thermo Fisher Scientific: MOSH/MOAH Analysis - Technology, Regulation, and the Road Ahead" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_MOSH_MOAH_Analysis_Technology_Regulation_and_the_Road_Ahead_2_f79d1ed4ee.jpg 245w," sizes="100vw" width="1200" height="600">These compounds—originating from sources such as environmental pollution, lubricants, processing aids, and migration from packaging materials—can enter the food chain and accumulate in both raw ingredients and finished products.<ul><li>MOSH are saturated hydrocarbons, which can accumulate in human tissues but are generally considered of lower toxicological concern.</li><li>MOAH contain aromatic rings, including polycyclic structures; certain high-ring MOAH are suspected to have genotoxic and carcinogenic properties, making them a priority for regulatory control.</li></ul>Growing public awareness, coupled with scientific research and legislative pressure, is pushing the food industry toward more robust monitoring and testing.<h4>The evolving regulatory landscape</h4>For years, MOSH/MOAH testing lacked consistent rules across jurisdictions. Different countries and organizations used their own limits and methods, creating confusion for global supply chains. Over the last decade, several important steps have brought the field closer to harmonization:<h5>2017 – EN 16995 (CEN)</h5><ul><li>The first standardized method for quantifying MOSH and MOAH in foodstuffs using LC-GC-FID technology.</li></ul><h5>2023 – JRC Guidelines v2</h5><ul><li>Expanded scope to include food contact materials, with refinements in sample preparation and measurement.</li></ul><h5>2024 – ISO 20122:2024</h5><ul><li>A dedicated standard for fats and oils, integrating clean-up procedures alongside LC-GC-FID to improve accuracy.</li></ul><h5>Ongoing – EURL/ISO initiatives</h5><ul><li>Collaborative efforts including interlaboratory studies, method refinement, and the potential adoption of GC×GC–MS for enhanced selectivity and molecular insight.</li></ul>A major development still in progress is the EU’s draft regulation for maximum residue limits for MOAH. Expected after 2024, it could introduce strict, enforceable thresholds across the single market, forcing a step-change in testing capacity and method validation.<h4>Analytical challenges in MOSH/MOAH testing</h4>Although standardized methods exist, MOSH/MOAH analysis is not a straightforward “plug-and-play” process. Laboratories face several persistent challenges:<h5>Complex sample matrices</h5><ul><li>Edible oils, processed foods, and packaging extracts contain a mix of natural compounds such as carotenoids, terpenes, and squalene. These can overlap chromatographically with MOSH/MOAH peaks, making quantification more difficult.</li></ul><h5>False positives and overestimation</h5><ul><li>Non-MOSH/MOAH compounds can mimic the target analytes, especially in less selective detection modes, leading to inflated results.</li></ul><h5>Low detection limits</h5><ul><li>Many regulations demand quantification in the low mg/kg range. Achieving this requires both clean sample extracts and highly sensitive analytical instrumentation.</li></ul><h5>Reproducibility across labs</h5><ul><li>Differences in sample handling, clean-up techniques, and instrument tuning can lead to significant interlaboratory variation, complicating compliance and enforcement.</li></ul>These challenges mean that achieving accuracy, repeatability, and regulatory compliance requires optimized workflows that combine precision sample preparation with advanced chromatographic techniques.<h4>A modern workflow: from sample to result</h4>State-of-the-art MOSH/MOAH workflows are typically built around an LC-GC-FID platform supported by automated sample preparation. This integration reduces human error, improves throughput, and delivers reproducible results.<h5>Step 1: saponification</h5>Fats can overwhelm LC columns, limiting injection volumes and obscuring MOSH/MOAH peaks. Saponification removes these fats, enabling:<ul><li>Larger injection volumes.</li><li>Clearer chromatographic baselines.</li><li>Lower quantitation limits without compromising peak integrity.</li></ul><h5>Step 2: epoxidation</h5>For MOAH analysis, carotenoids, terpenes, and other naturally occurring compounds must be removed. Epoxidation—now most commonly performed using PFA reagents—cleans up these interferences while maintaining the integrity of aromatic hydrocarbons.<h5>Step 3: evaporation and concentration</h5>By concentrating the hexane extract after saponification, laboratories can:<ul><li>Achieve lower detection limits.</li><li>Improve recovery from challenging matrices such as palm stearates.</li></ul><h5>Step 4: alu oxide clean-up</h5>Adding an alumina oxide clean-up step can substantially improve MOSH quantification in the presence of n-alkanes. This step is matrix-dependent and should be avoided if n-alkanes are absent to prevent bias.<h5>Step 5: fraction collection for advanced analysis</h5>When further identification is required—such as distinguishing between mineral oil hydrocarbons and plasticizers (POSH)—fraction collection followed by GC×GC-MS analysis can provide a deeper chemical fingerprint.<h4>Beyond “how much”: the role of GC×GC-MS</h4>Conventional LC-GC-FID answers the fundamental question: How much MOSH or MOAH is present in the sample?But it cannot always explain the source or the chemical nature of the detected hydrocarbons.This is where GC×GC-MS adds value:<ul><li>Source tracing – Identifies whether contamination originates from packaging, processing equipment, or environmental exposure.</li><li>Structural characterization – Distinguishes low-ring MOAH (less concerning) from high-ring MOAH (more concerning toxicologically).</li><li>False positive elimination – Confirms the identity of suspect peaks, reducing the risk of misreporting.</li></ul>By combining FID for precise quantification with MS for molecular identification, GC×GC-MS enables both regulatory compliance and investigative insight.<h4>The role of chromeleon software in MOSH/MOAH analysis</h4>Modern analytical systems rely heavily on software to ensure speed, traceability, and accuracy. Chromeleon software offers:<ul><li>Unified control of LC, GC, and sample preparation hardware from a single interface.</li><li>Automated workflow setup – In just a few clicks, vial positions, injection types, and processing methods are assigned.</li><li>Integrated quality checks – Internal standard verification and retention time monitoring are built-in.</li><li>Customizable, regulatory-ready reports – Exportable in PDF, CSV, XML, and other formats without external spreadsheets.</li></ul>The result is streamlined operation, reduced analyst intervention, and consistent compliance with good laboratory practice (GLP) requirements.<h4>Looking ahead</h4>With upcoming EU regulations likely to set strict MOAH limits, and with continued scientific scrutiny of MOSH accumulation, the demand for high-quality testing will only increase.Key trends shaping the future of MOSH/MOAH analysis include:<ul><li>Wider adoption of GC×GC-MS for confirmation and source identification.</li><li>Greater automation in sample preparation to increase throughput and reproducibility.</li><li>Regulatory harmonization, which will help reduce discrepancies between international markets.</li><li>Lower detection thresholds, requiring even more sensitive and selective methods.</li></ul>For laboratories, the challenge is twofold: staying ahead of compliance requirements while building capacity for high-volume, high-accuracy testing. Those that invest in robust, automated, and harmonized workflows now will be better positioned to meet both current and future demands.<blockquote>Acknowledgement: Jorn Hofsteenge, SampleQ, Breda, The Netherlands</blockquote>

MOSH/MOAH Analysis: Technology, Regulation, and the Road Ahead

Labs use up to 10 times more energy than offices. Here’s how you can work to help change the trend by lowering your carbon footprint.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_A_Greener_HPLC_Guide_How_ACT_Labels_Help_Promote_Lab_Sustainability_1794553f3a.jpg" alt="Thermo Fisher Scientific: A Greener HPLC Guide - How ACT Labels Help Promote Lab Sustainability" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_A_Greener_HPLC_Guide_How_ACT_Labels_Help_Promote_Lab_Sustainability_1794553f3a.jpg 245w," sizes="100vw" width="1200" height="600">The reality is that labs are a major source of environmental impact.According to the National Renewable Energy Laboratory, the average lab typically consumes 3-10 times more energy than a typical office building!As sustainability becomes increasingly central to institutional goals, the lab environment must evolve to reflect these priorities. But simply recycling lab waste is not enough.Building a sustainable lab requires a holistic approach. A fundamental re-think on how to minimize your environmental impact.From developing waste-reducing methods to prioritizing sustainable procurement, and even new approaches in green chemistry can help lower your lab’s carbon footprint.<h4>The future is regulated, let’s get ahead of the curve</h4>The push for greener methods is more than an internal movement and now driven by a growing number of regulatory bodies.Agencies like the European Medicines Agency (EMA) and the U.S. Environmental Protection Agency (EPA) are increasingly prioritizing environmental risk assessments and green chemistry principles. This shift signals that regulations governing solvent usage, waste disposal, and overall environmental impact are becoming more stringent.And the future of analytical chemistry is one where greener methods may become mandatory by regulators. This potential change makes adopting modern methods and sustainable procurement strategic imperatives for labs seeking to get ahead of the curve.This need for change is particularly relevant for core analytical techniques used in labs every day, such as High-Performance Liquid Chromatography (HPLC), which are significant sources of emissions and waste.<h5>The primary contributors to the environmental impact of HPLC include:</h5><ul><li>Energy consumption of your instrument</li><li>Solvent/chemical usage and toxicity</li><li>Total waste generation volume</li><li>Single use consumables</li></ul>Beyond the daily operation, sustainability also requires us to look upstream at the manufacturing practices that create our lab equipment.<ul><li>Using renewable energy in development and manufacturing</li><li>Percentage of recycled/renewable product packaging</li><li>Longevity, and end-of-life recyclability for products</li></ul><h4>How to make better choices for our planet</h4>The good news is that you (we!) don’t have to wait for change. Every scientist can make a difference today by carefully considering their choices. The shift toward an eco-conscious lab starts with the small decisions you make every day.Here are some key ideas to consider for a more sustainable HPLC workflow:<h5>Adopt modern analytical methods</h5><ul><li>Using <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/cz/en/home/industrial/chromatography/chromatography-learning-center/chromatography-consumables/consumable-types.html">shorter columns with smaller particles</a>, you can often achieve faster results while significantly reducing the volume of solvents and mobile phase required.</li></ul><h5>Avoid using toxic solvents when possible</h5><ul><li>Consider replacing hazardous solvents like acetonitrile with greener alternatives like ethanol. This switch not only improves safety but also reduces the environmental impact of your waste stream.</li></ul><h5>Re-think your detection</h5><ul><li>Omitting the use of derivatization techniques where possible is another way to reduce chemical consumption, as these steps often require toxic reagents and generate more waste.</li></ul><h5>Prioritize sustainable suppliers</h5><ul><li>Just as we analyze our own practices, we must look at our supply chain. Choose companies that prioritize sustainable growth and manufacturing as their practices—from product design to sustainable packaging—directly impact the planet.</li></ul>Ultimately, making these choices requires clear, trustworthy information.This decision making is where ACT labels come in.<h4>What is the ACT label?</h4>To help labs identify sustainable equipment, the non-profit organization <a target="_blank" rel="noopener noreferrer" href="https://mygreenlab.org/programs/act-ecolabel/">My Green Lab</a> developed the <a target="_blank" rel="noopener noreferrer" href="https://mygreenlab.org/programs/act-ecolabel/#act-2-0-features">ACT® Ecolabel</a>. ACT stands for Accountability, Consistency, and Transparency, and serves as a trusted third-party certification that provides clear, comprehensive information about the environmental impact of laboratory products.You can think of the ACT label as a nutrition label for your lab supplies. It provides a score based on a product’s Environmental Impact Factor (EIF) across key categories: Manufacturing, User Impact, and End of Life. The criteria within these categories cover everything from energy and water consumption to sustainable packaging and product longevity.A higher score (Figure 1) indicates a lower environmental impact, making it easy for you to compare products and make purchasing decisions that support your sustainability goals.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Figure_1_Lab_certification_levels_for_ACT_labels_1e1b5be65f.jpg" alt="Thermo Fisher Scientific: Figure 1. Lab certification levels for ACT labels" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Figure_1_Lab_certification_levels_for_ACT_labels_1e1b5be65f.jpg 245w," sizes="100vw" width="700" height="410"><h4>Our commitment to ACT Label 2.0</h4>Energy consumption is one of the largest contributors to the lifecycle carbon emissions of an HPLC or UHPLC instrument, having potentially even a greater contribution than solvent consumption or instrument manufacturing.At Thermo Fisher Scientific, we value the importance of transparency in sustainability and are committed to guiding our customers in making environmentally informed purchasing decisions. To reinforce this commitment, we partnered with My Green Lab to incorporate the new ACT® Ecolabel 2.0 into our product offerings. We’re proud to announce our <a target="_blank" rel="noopener noreferrer" href="https://actdatabase.mygreenlab.org/?manufacturer=6&amp;product_type=29">Thermo Scientific Vanquish HPLC &amp; UHPLC Systems received a Platinum rating</a> (Figure 2)! This rating is the second highest possible certification level, reflecting our dedication to reducing environmental impact across the entire product lifecycle—from design and manufacturing to energy efficiency and end-of-life recyclability.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Figure_2_ACT_Ecolabel_for_Vanquish_Core_Binary_HPLC_System_6c67c2a891.jpg" alt="Thermo Fisher Scientific: Figure 2. ACT Ecolabel for Vanquish Core Binary HPLC System" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Figure_2_ACT_Ecolabel_for_Vanquish_Core_Binary_HPLC_System_6c67c2a891.jpg 245w," sizes="100vw" width="700" height="410"><h4>Our ongoing pledge to sustainability, in and out of the lab</h4>Explore how moving from traditional HPLC to UHPLC methods can increase your lab’s productivity with higher throughput and less solvent.<ul><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/xx_002781_lc_vanquish_method_moderization_guide_tip_sheet_xx002781_en_aca7492d0b.pdf">A Helpful Guide to Modernizing Your Old HPLC Methods</a></li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/in_003058_hplc_vanquish_systems_sanofi_productivity_method_modernization_in003058_na_en_5c74552930.pdf">Infographic: Sanofi – Accelerating your lab operations&nbsp;</a></li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/cs_003059_hplc_vanquish_systems_sanofi_productivity_case_study_cs003059_na_en_25d72a56d5.pdf">Case Study: Transferring methods onto a new UHPLC platform&nbsp;</a></li></ul>Discover how we are innovating with the planet in mind and integrating sustainability into our product development.<ul><li><a target="_blank" rel="noopener noreferrer" href="https://corporate.thermofisher.com/us/en/index/corporate-social-responsibility.html">Our Corporate Social Responsibility page</a></li><li><a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/cz/en/home/sustainable-design.html">Greener by Design&nbsp;</a></li></ul><blockquote>Visit us on <a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/chromatography-&amp;-mass-spectrometry/">LinkedIn</a>: #LabOfFuture #LiquidChromatography #ClimateChangeMegan KennyMegan Kenny is a Product Marketing Manager for HPLC products at Thermo Fisher Scientific. She supports creating high-value and compelling content from product tours and configurators to literature and troubleshooting tips. She ensures users have easy access to product content across the Thermo Fisher website. Megan graduated from Drexel University in Philadelphia, PA, in 2013 with her Bachelor's of Science in marketing and has worked in the chromatography and mass spectrometry space since. She is passionate about translating technical information into compelling content.</blockquote>

A Greener HPLC Guide: How ACT Labels Help Promote Lab Sustainability

In the realm of pharmaceutical manufacturing, the detection and analysis of perfluoroalkyl substances (PFAS) have become a growing source of concern due to their persistence and potential health risks. The latest application note from SGS presents a groundbreaking approach to PFAS screening and quantification, leveraging the capabilities of the Thermo Scientific Vanquish UHPLC and Orbitrap Exploris 120 high-resolution mass spectrometer (HRAM-MS).This application note demonstrates the sensitive detection and identification of both known and unknown PFAS compounds in extracts from common pharmaceutical manufacturing and packaging materials. By employing a combined targeted and non-targeted approach, the study highlights how the integration of the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=40&amp;manufacturerItems=3">Vanquish UHPLC </a>and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/403">Orbitrap Exploris 120 HRAM-MS</a> can revolutionize PFAS analysis.<h5>The key benefits of this method include:</h5><ul><li>Combined Targeted and Non-Targeted Screening: One injection allows for both the quantitation of specific PFAS compounds and the screening for additional, previously unidentified PFAS contaminants.</li><li>Enhanced Analytical Confidence: The use of a PFAS analysis kit and delay column minimizes background PFAS interference, thereby increasing the reliability of the results.</li><li>Regulatory Compliance: Utilizing <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/76">Chromeleon CDS </a>ensures that the data acquisition and quantitative analysis comply with 21 CFR Part 11, a crucial requirement for pharmaceutical applications.</li><li>High Sensitivity and Specificity: The method provides unequivocal identification and quantification of PFAS compounds down to sub-ppb levels.</li></ul>The study underscores the efficacy of the Orbitrap Exploris 120 HRAM-MS in providing a comprehensive solution for PFAS analysis. By integrating both targeted and non-targeted approaches, this method not only enhances the detection sensitivity and specificity but also expands the scope of detectable PFAS contaminants. This dual approach is a significant advancement in extractables screening, offering pharmaceutical manufacturers a robust tool for ensuring the safety and compliance of their products.<blockquote><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_003388_pb_pfas_orbitrap_exploris_120_extractables_an003388_na_en_dd0e422ebd.pdf">Download our joint application note</a> to learn about Comprehensive PFAS screening in pharmaceutical packaging and medical devices by LC-HRAM-MS</blockquote>This collaboration between SGS and Thermo Fisher Scientific illustrates a leap forward in PFAS screening technology, promising higher quality results, increased confidence, and regulatory compliance in the pharmaceutical manufacturing process.<blockquote>Jon BardsleyJon Bardsley is a Market Development Manager for Pharma and Biopharma with Thermo Fisher Scientific.</blockquote>

Advancing PFAS Detection in Pharmaceutical Manufacturing with LC-HRAM-MS

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Advancing PFAS Detection in Pharmaceutical Manufacturing with LC-HRAM-MS

A Greener HPLC Guide: How ACT Labels Help Promote Lab Sustainability

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