Struggling to accurately measure semi-volatile analytes? Stricter temperature control with HPLC-CAD analysis just might be the solution you need.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_How_to_Get_More_Accurate_HPLC_Quantitation_of_Semi_Volatiles_1_f2eefd5901.jpeg" alt="Thermo Fisher Scientific How to Get More Accurate HPLC Quantitation of Semi-Volatiles" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_How_to_Get_More_Accurate_HPLC_Quantitation_of_Semi_Volatiles_1_f2eefd5901.jpeg 245w," sizes="100vw" width="1024" height="512">The charged aerosol detector (CAD) is cited as one of the most capable near-universal HPLC detectors available because the response is solely based on particle charge and fully independent of chemical structure.One caveat to know is your mobile phase components must be less volatile than the analytes in solution for detection by the CAD. And while all non-volatiles give a similar uniform response, <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/chromatography/chromatography-learning-center/liquid-chromatography-information/hplc-system-components/how-hplc-detectors-work/charged-aerosol-detection/charged-aerosol-detection-cad-performance-tips.html">the response of semi-volatiles</a> depends on volatility and consequently is less predictable.So, the question then becomes is there a way to address this performance difference and make semi-volatile detection more predictable? One approach for charged semi-volatile analytes is to add a volatile ion-pairing agent of the opposite charge in the mobile phase to force non-volatile behavior.However, this method is analyte specific and may also react with impurities in your mobile phase, leading to higher noise and poorer signal-to-noise (S/N) ratio. What’s really needed is a more global approach to improve the accuracy for measuring semi-volatiles.This approach is now achievable with Temperature Coupling Mode (TCM) in the <a target="_blank" rel="noopener noreferrer" href="https://discover-pharma.com/thermo-fisher-upgrades-charged-aerosol-detection-tech-to-improve-complex-drug-analysis/">Thermo Scientific Vanquish CAD P Series</a>.<h3>Why stricter temperature control matters for measuring semi-volatiles</h3>Before we get into the specifics, you need to understand why temperature control in the CAD is critical to quantitative accuracy, especially for semi-volatiles (Figure 1).<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_How_to_Get_More_Accurate_HPLC_Quantitation_of_Semi_Volatiles_2_e33cff4cac.jpeg" alt="Thermo Fisher Scientific: How to Get More Accurate HPLC Quantitation of Semi-Volatiles: Figure 1. Illustration showing how the CAD works." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_How_to_Get_More_Accurate_HPLC_Quantitation_of_Semi_Volatiles_2_e33cff4cac.jpeg 245w," sizes="100vw" width="1024" height="512">The two <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/chromatography/chromatography-learning-center/liquid-chromatography-information/hplc-system-components/how-hplc-detectors-work/charged-aerosol-detection.html">most important functional components in the CAD that guide sensitivity</a> are the evaporation tube temperature (EvapT) and the charging detection module (CDM).<ul><li>EvapT plays a crucial role in determining the performance of the detector, and changing this temperature may alter analyte “selectivity”</li><li>The CDM is where particle charge and measurement happen</li></ul>In previous CAD models, the EvapT is adjustable, but the temperature of the CDM is permanently set at 40 °C. This fixed temperature difference between the EvapT and CDM could negatively impact the measurement of semi-volatile compounds that require a lower EvapT.Adding TCM resolves this issue, by linking the EvapT and CDM temperatures, thereby improving the quantitation of semi-volatile species.<h3>Using TCM to help improve quantification of semi-volatiles, like fatty acids</h3>To demonstrate the effectiveness of this new temperature coupling feature, we anlazyed a working solution of four individual fatty acids (FAs) and compared the CAD repsonse with TCM turned on and turned off (Figure 2).<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_How_to_Get_More_Accurate_HPLC_Quantitation_of_Semi_Volatiles_3_da6cf5006c.jpeg" alt="Thermo Fisher Scientific: How to Get More Accurate HPLC Quantitation of Semi-Volatiles: Figure 2. The mean S/N ratio of the FAs analyzed with TCM turned on and off." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_How_to_Get_More_Accurate_HPLC_Quantitation_of_Semi_Volatiles_3_da6cf5006c.jpeg 245w," sizes="100vw" width="700" height="410">Notably, we observed 46.8% increase in the S/N at the optimal EvapT of 25 °C and with the TCM switched on for lauric acid, the most semi-volatile compound!Interestingly, the observed S/N improvement matches the respective analyte volatility—lauric acid (lowest MW) shows the greatest improvement, and stearic acid (highest MW) the least.Taken together, these findings show how stricter temperature control in the CAD can allow you to extend the range and improve quantification of semi-volatiles.<h3>Extending this application to impurity analysis of polysorbates</h3>Now that we’ve seen TCM is useful for analyzing fatty acids, let’s consider more complex solutions, like polysorbates.Given the CAD is well-established for determining <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0021967324010240?via%3Dihub">polysorbate impurities</a>, and fatty acid impurities are quite abundant in polysorbates, and a logical next step is to use this technique for analyzing these solutions.Afterall, free acids in polysorbates <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/blog/analyteguru/review-of-analytical-methods-for-quantifying-amp-profiling/">may form insoluble particles</a> that can seriously compromise product quality, efficacy, and patient safety. Thus, your ability to accurately measure these acids in raw materials and finished goods is of the upmost importance.Download our paper to see how the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_003867_hplc_vanquish_cad_gradient_optimized_evap_temp_an003867_na_en_b64411eb47.pdf">Vanquish CAD P Series</a> can help your lab measure fatty acids with greater confidence today.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_How_to_Get_More_Accurate_HPLC_Quantitation_of_Semi_Volatiles_4_70473e3696.jpeg" alt="Thermo Fisher Scientific: How to Get More Accurate HPLC Quantitation of Semi-Volatiles: Figure 3. Thermo Scientific Vanquish CAD P Series" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_How_to_Get_More_Accurate_HPLC_Quantitation_of_Semi_Volatiles_4_70473e3696.jpeg 245w," sizes="100vw" width="700" height="410"><h3>FAQs</h3><ol><li>What are the advantages of using a charged aerosol detector for HPLC analysis?</li></ol>The <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/c/b/vanquish-charged-aerosol-detector-p-series.html">charged aerosol detector</a> (CAD) is now recognized as the most capable “universal” detector available and offers several advantages over other UHPLC-based detectors including:<ul><li>Uniform response for all non-volatile analytes (ideal for quantitation when certified standards are unavailable)</li><li>Universal response independent of chemical structure (analyte does not have to form gas phase ions or possess a chromophore)</li><li>High sensitivity at high pg to low ng on column (ideal for drug impurity analysis)</li><li>Wide linear and dynamic range (measure API and impurities in one run)</li><li>Simple calibration curves (no need to deal with complex, unpredictable sigmoidal calibration curves)</li><li>Gradient compatible (inverse gradient available to ensure consistent response throughout the gradient)</li></ul><ol start="2"><li>Why should I use CAD for measuring fatty acid impurities in polysorbates?</li></ol>Fatty acids don’t contain strong chromophores, so HPLC-CAD analysis is the <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/blog/analyteguru/cad-vs-elsd-which-hplc-detector-is-your-better-option/">ideal choice</a> since the detector response depends on particle charge and is independent of analyte structure.<ol start="3"><li>How does changing the evaporation tube temperature affect the CAD response for semi-volatiles?</li></ol>A high EvapT can <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/tn_72806_uhplc_charged_aerosol_detection_tn72806_en_5979117651/tn-72806-uhplc-charged-aerosol-detection-tn72806-en.pdf">improve sensitivity</a> for non-volatiles by reducing noise but may negatively impact measurement of semi-volatile species. Conversely, a lower EvapT can improve the detection of semi-volatile species, but sensitivity for all analytes may be adversely impacted due to increased noise.Visit us on&nbsp;<a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a>&nbsp;#HPLC #CAD #biopharma<section><blockquote><h5>Dr. Kimberly M. Lincoln</h5>Dr. Kimberly M. Lincoln is a marketing specialist in the HPLC division at Thermo Fisher Scientific. She holds a Ph.D. in bioinorganic chemistry and a B.S. in chemistry, with professional experience in digital marketing, medical device manufacturing, and chemical synthesis. Kimberly enjoys writing educational chemical content as a guide to help customers solve analytical problems. She is passionate about living a clean lifestyle and keeping the planet healthy for future generations. In her spare time, Kimberly loves to cook, cycle, attend rock concerts, and spend time with her pit bulls.</blockquote></section>

How to Get More Accurate HPLC Quantitation of Semi-Volatiles

We are pleased to announce that a maintenance release is now available for KnowItAll 2026. Maintenance releases are an important way to introduce improvements and bug fixes between major releases to make sure users get the most out of KnowItAll.In Fall 2025, we announced the KnowItAll 2026 major release featuring a new principal component analysis tool, Trendfinder, and various advances for spectral analysis workflows. This is the first update available after that release.<h5>Updates in the 2026.1 maintenance release include:</h5><ul><li>Continued to LC-MS deconvolution improvement</li><li>Updated the DEA regulations rulebase that’s used to automatically categorize structures in databases you build in MineIt according to current Drug Enforcement Agency controlled substance regulations.</li><li>Various bug fixes</li></ul>We encourage users to update now to the most recent version of the software to ensure the best performance.<ul><li><a target="_blank" rel="noopener noreferrer" href="https://get.knowitall.com/Download?_gl=1*18h0vjr*_gcl_au*Mjk3ODY0Mzg1LjE3MTMyNzcyMDEuMTkwNDkyNDI4NS4xNzEzMzY3NDc0LjE3MTMzNjc0Nzk.">Download the most recent version here</a></li><li><a target="_blank" rel="noopener noreferrer" href="https://sciencesolutions.wiley.com/whats-new-in-knowitall-2026/">What's New in KnowItAll 2026</a></li><li><a target="_blank" rel="noopener noreferrer" href="https://sciencesolutions.wiley.com/knowitall-version-history/">KnowItAll version history</a></li></ul><h4>About KnowItAll</h4>KnowItAll Software offers solutions to analyze and manage multiple types of spectral and chemical data in multiple file and instrument formats. KnowItAll's integrated toolsets eliminate the need for multiple software packages and increase overall lab efficiency and staff proficiency. Combined with Wiley’s comprehensive, high-quality spectral reference libraries, it provides an unparalleled solution for fast, reliable spectral analysis. Learn more.<h4>About <a target="_blank" rel="noopener noreferrer" href="https://www.wiley.com/en-ie/">Wiley</a></h4>Wiley (NYSE: WLY) is a global leader in authoritative content and research intelligence for the advancement of scientific discovery, innovation, and learning. With more than 200 years at the center of the scholarly ecosystem, Wiley combines trusted publishing heritage with AI-powered platforms to transform how knowledge is discovered, accessed, and applied. From individual researchers and students to Fortune 500 R&amp;D teams, Wiley enables the transformation of scientific breakthroughs into real-world impact. From knowledge to impact—Wiley is redefining what's possible in science and learning. Visit us at Wiley.com and Investors.Wiley.com. Follow us on Facebook, X, LinkedIn and Instagram.

KnowItAll 2026.1 maintenance release now available - Upgrade for the latest features and fixes

<h3>Introduction</h3>Modern analytical laboratories often operate multiple chromatographic instruments simultaneously, which places high demands on software usability and workspace navigation. <a target="_blank" rel="noopener noreferrer" href="https://gcms.labrulez.com/products/999">Clarity Chromatography Software</a> developed by DataApex provides a structured, instrument-oriented user interface designed to simplify work even in complex multi-instrument environments. This article explains how to efficiently move between windows in Clarity.<h3>Concept of Instrument-Centric Workspace Organization</h3><h4>Instrument-Specific Color Schemes</h4>Each instrument in Clarity is visually distinguished by its own color scheme. This design choice allows users to:<ul><li>Instantly recognize which windows belong to the same instrument</li><li>Avoid confusion when multiple instruments are open simultaneously</li><li>Maintain orientation within complex analytical workflows</li></ul>Color coding is consistent across all windows associated with a given instrument.<h3>Types of Windows in Clarity</h3>Within a single instrument context, Clarity typically provides access to several interconnected windows, including:<ul><li>Instrument Window – the central control and overview window</li><li>Chromatogram Window – displays acquired chromatographic data</li><li>Sequence Window – manages sample sequences and runs</li></ul>Efficient navigation between these windows is essential for smooth operation.<h3>Navigation Methods Between Windows</h3>Clarity offers multiple complementary ways to switch between related windows. Users can choose the method that best fits their workflow preferences.<h4>1. Instrument Window Tiles</h4>Within the Instrument Window, large tiles represent related windows.Example workflow:<ul><li>Select the large chromatogram tile to switch directly from the Instrument Window to the Chromatogram Window</li></ul>This tile-based approach is intuitive and visually guided.<h4>2. Toolbar Icons</h4>Each instrument window contains a toolbar with window icons that provide direct access to other related windows.Key characteristics:<ul><li>The same set of window icons is available across all instrument-related windows</li><li>Enables quick transitions, for example:<ul><li>From Chromatogram Window → Sequence Window</li></ul></li><li>Ideal for experienced users who prefer icon-based navigation</li></ul><h4>3. Window Menu</h4>For users who prefer menu-driven control, Clarity includes a Window menu.Typical use case:<ul><li>Select Main from the Window menu to return to the Clarity main window</li></ul>This method is particularly useful when:<ul><li>Navigating back to the global workspace</li><li>Managing multiple instruments at once</li></ul><h3>Practical Navigation Workflow Example</h3>A typical navigation sequence demonstrated in the video follows this logic:<ol><li>Start in the Instrument Window</li><li>Click the Chromatogram tile to open chromatographic data</li><li>Use the toolbar icon to switch to the Sequence Window</li><li>Open the Window menu and select Main to return to the Clarity main interface</li></ol>This combination of tiles, icons, and menus ensures flexible and efficient workspace control.<h3>Advantages of Clarity’s Navigation Design</h3>The navigation system in Clarity provides several practical benefits:<ul><li>Consistency – identical navigation tools across instrument windows</li><li>Efficiency – rapid switching without losing context</li><li>Scalability – effective even with many instruments open</li><li>User preference flexibility – toolbar or menu-based workflows</li></ul>These features are especially valuable in high-throughput laboratories and 24/7 operational environments.<h3>Conclusion</h3>Clarity Chromatography Software uses a well-structured, instrument-oriented window system that simplifies navigation even in complex multi-instrument setups. By combining color-coded instruments, tile-based access, universal toolbar icons, and traditional menus, Clarity allows users to move quickly and confidently between windows.Mastering these navigation techniques significantly improves workflow efficiency, reduces errors, and enhances overall user experience—making Clarity a robust platform for modern chromatographic laboratories.For additional tutorials and practical demonstrations, users are encouraged to explore further educational resources provided by DataApex.

How to switch between the Clarity Windows

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How to Get More Accurate HPLC Quantitation of Semi-Volatiles