Our Library never stops expanding. What are the most recent contributions to LabRulezLCMS Library in the week of 22nd September 2025? Check out new documents from the field of liquid phase, especially HPLC and LC/MS techniques!<blockquote>👉 <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library">SEARCH THE LARGEST REPOSITORY OF DOCUMENTS ABOUT LCMS AND RELATED TECHNIQUES</a></blockquote><blockquote>👉 Need info about different analytical techniques? Peek into <a target="_blank" rel="noopener noreferrer" href="https://gcms.labrulez.com/library">LabRulezGCMS</a> or <a target="_blank" rel="noopener noreferrer" href="https://icpms.labrulez.com/library">LabRulezICPMS</a> libraries.</blockquote>This week we bring you application notes by Agilent Technologies, Shimadzu and Waters Corporation and poster by Thermo Fisher Scientific / HPLC Symposium!<h3>1. Agilent Technologies: Quantitation of N-Nitroso Nebivolol in Nebivolol Tablet Formulation</h3>Using an <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=6495D+triple+quadrupole">Agilent 6495D triple quadrupole LC/MS system</a><ul><li>Application note</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_nebivolol_tablet_formulation_6495_qqq_lc_ms_system_5994_8053en_agilent_e7f21eb12f.pdf">Full PDF for download</a></li></ul>N-Nitroso Nebivolol is a NDSRI of Nebivolol, a beta-1 adrenergic receptor antagonist commonly used in the treatment of hypertension and heart failure. In the carcinogenic potency categorization published by the FDA, N-Nitroso Nebivolol has been categorized as Class 4, indicating the maximum allowable intake limit for the impurity to be 1,500 ng/day. Nebivolol has maximum daily dosage limit of 40&nbsp;mg for adults.Considering a maximum daily dose of 40&nbsp;mg and allowable intake of 1,500&nbsp;ng/day for the nitrosamine impurity in the formulation under study, the specification limit of N-Nitroso Nebivolol has been calculated as 22.5 ng/mL for the 0.6 mg/mL test concentration used during this study.&nbsp;This application note demonstrates a highly specific, sensitive, and reproducible method for the quantitation of N-Nitroso Nebivolol in a 20 mg Nebivolol tablet formulation. The method uses a 1290 Infinity II LC coupled to a 6495D triple quadrupole LC/MS/MS. The multiple reaction monitoring (MRM) conditions and ion source parameters were automatically optimized using the optimizer tool available with MassHunter Acquisition software to maximize the sensitivity of the target analyte. The API peaks were diverted to waste with the help of an integrated, software-controlled diverter valve during quantitation of the&nbsp;impurity.<h4>Experimental</h4><h5>Equipment&nbsp;</h5>The analysis was performed on a <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=1290+Infinity+II+LC">1290 Infinity II LC system</a> coupled to a <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=6495D+triple+quadrupole">6495D triple quadrupole LC/MS/ MS</a>. The LC system was equipped with the following&nbsp;modules: – Agilent 1290 Infinity II high-speed pump (G7120A) – Agilent 1290 Infinity II multisampler (G7167B) – Agilent 1290 Infinity II multicolumn thermostat (G7116B) – Agilent 1290 Infinity II diode array detector (G7117A)<h4>Conclusion&nbsp;</h4>A highly sensitive and robust MRM method was developed for the quantitation of N-Nitroso Nebivolol in 20&nbsp;mg Nebivolol tablet formulation using an Agilent 6495D triple quadrupole LC/MS system. The chromatographic method developed provided good separation between the analyte and the API. The method showed LOD and LOQ of 2 and 5 pg/mL, respectively. The minimum signal-to-noise ratio at the LOQ level was found to be more than 50:1 (Peak to Peak). The calibration curve from 5 pg/mL to 50&nbsp;ng/mL was found to be linear, with 1/x weighting. R and R2 values were 0.999 and 0.997, respectively. Spike recovery analysis showed the efficiency of sample extraction with a recovery percentage of 116.8% in API, 108.3% in placebo, and 111.8% in tablet formulation at the spiking level of 200 pg/mL. The method was found to be highly reproducible at the LOQ level, while the %RSD value for the area response of seven replicate injections was approximately 3.1%.<h3>2. Shimadzu: Efficient Method Development for Synthetic Peptide and Related Impurities</h3><ul><li>Application note</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_01_00780_en_4d0aa014ea.pdf">Full PDF for download</a></li></ul><h5>User Benefits</h5><ul><li>LabSolutions MD improves the efficiency of the entire workflow for method development of synthetic peptide and impurities.&nbsp;</li><li>Screening for multiple mobile phases and columns can be automated using mobile phase and column switching valves.&nbsp;</li><li>Molecular weights of peptides and related impurities can be estimated and accurately tracked with LCMS-2050, a single quadrupole mass spectrometer.</li></ul>Peptide therapeutics, characterized by specific amino acid sequences crucial to their function, can be synthesized chemically, similar to small molecule drugs. The production of synthetic peptides involves multiple steps, including deprotection, activation, coupling, and the cleavage of the final sequence from the solid support. Impurities, such as those resulting from premature chain termination or missing amino acids, can affect the safety and efficacy of the final product. Therefore, these impurities must be separated by liquid chromatography (LC). In LC analysis, selecting the appropriate mobile phase and column across a wide range of combinations is critical for achieving optimal separation, as it significantly impacts the separation. However, since the separation pattern varies depending on the peptide chain lengths, amino acid compositions, and presence of modifications, optimizing separation for each peptide sequence is time-intensive. This study describes how to efficiently find the best separation conditions for peptides and related impurities utilizing LabSolutions MD, a dedicated software for supporting method development, through both screening and optimization phases.<h4>Experimental</h4><ul><li>LC System: <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=1&amp;search=Nexera+X3">Nexera X3</a> (Method Scouting System)</li><li>MS System: <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=1&amp;search=LCMS-2050">LCMS-2050</a></li></ul><h4>Automated Peak Tracking by LCMS-2050&nbsp;</h4>LC chromatograms obtained with a gradient time of 5 min, flow rate of 0.6 mL/min, and initial concentration of 5 % and 15 %, along with molecular weights for FLP and impurities, are shown in Fig. 18. The UV spectra for each impurity are displayed in Fig. 19. The similarity between UV spectra of Met(O2), p.A1del, p.A1_E2del, p.A1_K3del, and p.A1_D5del is greater than 0.99, suggesting that peak tracking based on UV spectra would be challenging. In contrast, LabSolutions MD enables peak tracking based on molecular weights acquired by LCMS-2050, facilitating accurate identification of compounds with similar UV spectra (Fig. 18). The estimated molecular weights for each compound show small mass errors compared to the theoretical values (Table 3), which can be used to confirm the molecular weights of known compounds as well as to approximate the molecular weights of unknown impurities.<h4>Conclusion</h4>The separation patterns of synthetic peptides vary depending on mobile phase composition, column type, and various LC parameters, such as gradient conditions, column oven temperature, and flow rate. Separation behavior can also differ based on peptide structure, including length, amino acid composition, and the presence of modifications. Therefore, it is necessary to optimize the separation for each peptide sequence individually. However, optimizing analytical conditions through numerous analyses and data processing can be time-consuming. LabSolutions MD automates the entire workflow, including generating analysis schedules, preparing mobile phases, and processing the data, thanks to functionalities such as automated peak tracking, ranking of chromatograms, and design space visualization. This article introduced a case where the optimal separation conditions for synthetic peptides were efficiently identified through screening and optimization phases. LabSolutions MD also offers fully automated gradient optimization by AI algorithm to meet user-defined criteria. For more details, please refer to the application news, “Automatic Optimization of Gradient Conditions by AI Algorithm on Synthetic Peptide and Impurities: 01-00814”.<h3>3. Thermo Fisher Scientific / HPLC Symposium: Sensitive cationic lipids impurities analysis with quantitation by charged aerosol detection and simultaneous mass confirmation by MS</h3><ul><li>Poster</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/po_sensitive_cationic_lipids_impurities_analysis_quantitation_po_en_3dacf61554.pdf">Full PDF for download</a></li></ul>Cationic lipid is a critical component in lipid nanoparticle formulations for delivering nucleic acids such as mRNA, siRNA, antisense oligonucleotides etc. [2] Cationic lipids are amphiphilic molecules that possess a hydrophilic region, a hydrophobic region, and a linker structure connecting the two. [1] Charged aerosol detector (CAD) and evaporative light scattering detectors (ELSD) are preferred for characterizing lipid nanoparticle components, with CAD being the better choice for impurity quantification due to its higher sensitivity [3]. In a previous study, an inverse gradient method was developed to quantify impurities in cationic lipids raw materials.[1] To demonstrate the inverse gradient method on CAD HP, the same cationic lipids -- R-DOTAP, DLin-KC2- DMA and ALC-0315 -- were measured to this experiment as in Application note 003384 [1]. New diverter valve and software features were showcased, along with method’s sensitivity and repeatability.<h4>Materials and methods</h4>Using the inverse gradient method from Application note 003384 [1], to demonstrate impurity analysis in cationic lipids on the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/2176">Thermo Scientific Vanquish Charged Aerosol Detector HP (CAD HP)</a> integrated in the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/743">Thermo Scientific Vanquish Flex Inverse Gradient UHPLC System</a>, with parallel mass confirmation by the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/413">Thermo Scientific ISQ EM Single Quadrupole Mass Spectrometer</a>.&nbsp;Methods: The workflow uses a <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/743">Vanquish Flex Inverse Gradient LC system</a> with Vanquish CAD HP and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1970">Thermo Scientific Hypersil GOLD C8 column</a>.<h5>Data Analysis&nbsp;</h5><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/76">Thermo Scientific Chromeleon Chromatography Data System (CDS)</a> 7.2.10 was used for data acquisition and analysis.<h4>Conclusions&nbsp;</h4>The CAD HP integrates perfectly into the Vanquish Inverse Gradient LC system and offers high sensitivity and excellent repeatability for quantitative cationic lipid impurity analysis, while the ISQ EM MS provides straightforward mass confirmation with high repeatability, all under compliance-ready conditions.<h3>4. Waters Corporation: Quantitative Analysis of Four Long-Chain Lysophosphatidylcholines (LPCs) in Dried Blood Spot using Liquid Chromatography Tandem Mass Spectrometry for Clinical Research</h3><ul><li>Application note</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/720008826_en_dc154872b6.pdf">Full PDF for download</a></li></ul><h5>Benefits</h5><ul><li>Good chromatographic resolution of all forms</li><li>Short extraction time compared to traditional methods for lipid extraction</li><li>Short analysis injection-to-injection 7 minutes</li></ul>Historically, very long chain fatty acids have been quantified using direct transesterification and gas chromatography methods which involve time-consuming and labor-intensive sample preparation and analysis. Consequently, simpler LC-MS/MS methods have been reported for the measurement of long-chain LPCs (LPCs generic chemical structure, Figure 1) in DBS. Interferences have been reported using positive ESI, thus researchers have developed methodologies utilizing negative ESI to circumvent isobaric interferences when there is lack of chromatographic resolution. Here a UHPLC-MS/MS method is described using acetate adducts for the reliable analysis of four long-chain LPCs in DBS for clinical research.&nbsp;A UHPLC-MS/MS method for quantifying a panel of LPCs (C20:0, C22:0, C24:0, and C26:0-LPCs) was developed. The mobile phase composition consisted of a mixture of water, acetonitrile, and isopropanol with 5 mM ammonium acetate as a modifier. The DBS sample extraction used a working solution prepared with the deuterated LPC internal standards in methanol. The method was developed with an ACQUITY UPLC I-Class PLUS System (Fixed Loop) using an ACQUITY Premier CSH C18 Column, which provided baseline resolution of endogenous isobaric interferences for the saturated forms of the targeted LPCs. The detector was a Xevo TQ-S micro Mass Spectrometer operated in negative ESI mode. This methodology resulted in a total analysis time (injection-to-injection) of 7 minutes.<h5>LC Conditions&nbsp;</h5><ul><li>LC system: <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/199">ACQUITY UPLC I-Class PLUS FL&nbsp;</a></li><li>System Detection: <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/209">Xevo TQ-S micro Mass Spectrometer&nbsp;</a></li><li>Plate: Waters 96-well Sample Collection Plate, 350 µL&nbsp;</li><li>Column(s): <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1952">ACQUITY Premier CSH C18 Column</a>, 2.1 mm x 50 mm, 1.7 µm (p/n: 186009460)</li></ul><h5>MS Conditions&nbsp;</h5><ul><li>MS system: Xevo TQ-S micro Mass Spectrometer</li></ul><h5>Data Management&nbsp;</h5><ul><li>MS software: <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/635">MassLynx™ v4.2 Software SCN 1045&nbsp;</a></li><li>Informatics: TargetLynx™ XS v4.2 Software SCN1045 and QUAN Review</li></ul><h4>Results and Discussion&nbsp;</h4>During method development, different types of column chemistry, mobile phase composition, and ESI polarity modes were assessed to optimize chromatographic peak shape, analytical sensitivity and manage interferences. In positive mode, ammonium formate favored the formation of m/z 184 and m/z 104 as daughter ions for all the LPCs. The m/z 184 ion lacks specificity because most phospholipids share this moiety, so the ion m/z 104 was selected as quantifier. Having evaluated conditions in positive mode for the analysis of the four saturated LPCs, it was observed that some existing interferences were not only affecting the parent masses of the analytes but their corresponding internal standard parent ion masses too. Hence, negative ionization using ammonium acetate as modifier was assessed for the detection of LPCs. Acetate adducts [M+CH3COO]- were the most abundant parent ion masses, generated under these conditions for each LPC. The acyl-chain product ions generated in negative ionization reduce the detection of interferences coming from other phosphocholine headgroups. The latter detection conditions were used for the validation of the method presented herein.<h4>Conclusion&nbsp;</h4>An LC-MS/MS clinical research method for measuring C20:0, C22:0, C24:0, and C26:0 LPCs with the ACQUITY UPLC I-Class PLUS FL System, and the Xevo TQ-S micro Mass Spectrometer that:<ul><li>Demonstrates good linearity, with no significant carryover, or matrix effects</li><li>Offers good precision with a total reproducibility and repeatability ≤10% CV</li><li>Offers reliability in the identification of LPCs from interfering isobaric compounds Provides good selectivity and analytical sensitivity in negative mode and is relatively fast as approximately 220 samples can be analyzed in 24 hours</li></ul>

News from LabRulezLCMS Library - Week 39, 2025

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

Welcome back to our series on Charged Aerosol Detection (CAD) in High-Performance Liquid Chromatography (HPLC). In our <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5390">first episode, we explored the fundamentals of CAD</a>. Today, we’ll take a closer look at how CAD stacks up against other universal detectors, specifically Evaporative Light Scattering Detection (ELSD) and Multi-Angle Light Scattering (MALS). By the end of this episode, you’ll understand why CAD is often the preferred choice for a wide range of analytical applications and the benefits of CAD over its competitors.<h4>Recap: What is charged aerosol detection (CAD)?</h4>To briefly recap, 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 works by nebulizing the liquid eluent from the HPLC column, drying the aerosol, charging the particles, and then detecting the charged particles. The signal generated is proportional to the mass of the analyte.<h4>Understanding ELSD and MALS</h4>Before we dive into the comparison, let’s briefly describe ELSD and MALS:<ul><li>Evaporative Light Scattering Detection (ELSD): ELSD nebulizes the eluent and evaporates the solvent, detecting the analyte particles by measuring the light scattered as they pass through a light beam. The response can be influenced by the size and refractive index of the particles.</li><li>Multi-Angle Light Scattering (MALS): MALS measures the intensity of light scattered at multiple angles by particles or macromolecules in a solution. It is often used to determine molecular weight and size, requiring complex data analysis.</li></ul><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Episode_2_The_Benefits_of_CAD_Compared_to_Other_Universal_Detectors_ELSD_and_MALS_063bfb3019.jpg" alt="Thermo Fisher Scientific: Episode 2 - The Benefits of CAD Compared to Other Universal Detectors - ELSD and MALS" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Episode_2_The_Benefits_of_CAD_Compared_to_Other_Universal_Detectors_ELSD_and_MALS_063bfb3019.jpg 114w," sizes="100vw" width="1125" height="1536"><h4>The benefits of CAD over ELSD and MALS</h4><ul><li>Uniform response: One of the most significant advantages of CAD is its consistent response across different analytes. Unlike ELSD, which can be influenced by particle size and refractive index, CAD provides a more uniform signal, simplifying quantification.</li><li>Higher sensitivity: CAD generally offers higher sensitivity compared to ELSD, making it suitable for trace analysis. While MALS can be highly sensitive for large molecules, it is less effective for small molecules.</li><li>Ease of use: CAD systems are user-friendly, with straightforward calibration and minimal sample preparation. This contrasts with ELSD, which requires careful optimization of nebulization and evaporation conditions, and MALS, which demands specialized knowledge for data interpretation.</li><li>Versatility: CAD can detect a broad range of non-volatile and semi-volatile compounds, making it applicable in various industries, from pharmaceuticals to environmental analysis. While ELSD is also versatile, its inconsistent response can be a limitation. MALS is primarily suited for macromolecules and polymers, limiting its applicability for small molecules.</li><li>Robustness: CAD is less prone to matrix effects, providing reliable data even in complex sample matrices. This robustness is a significant advantage in applications such as pharmaceutical impurity profiling and environmental testing.</li></ul><h4>Charged aerosol detection and evaporative light scattering detection – fundamental differences affecting analytical performance</h4>When comparing detection methods in liquid chromatography, Charged Aerosol Detection (CAD) stands out for its unique advantages. CAD charges aerosol particles, providing a consistent and uniform response regardless of particle size. This attribute simplifies calibration processes and enhances sensitivity, making CAD particularly effective for detecting a wide range of analytes with high precision. Unlike Evaporative Light Scattering Detection (ELSD), which measures light scattering and can result in non-linear calibration curves due to varying particle sizes, CAD ensures a more straightforward and reliable analytical performance. This consistency in response is crucial for achieving accurate and reproducible results, making CAD the preferred choice for many chromatographic analyses. For more details: <a target="_blank" rel="noopener noreferrer" href="https://documents.thermofisher.com/TFS-Assets/CMD/posters/PN-70990-CAD-Evaporative-Light-Scattering-Differences-Affecting-Performance-PN70990-EN.pdf">Charged Aerosol Detection and Evaporative Light Scattering Detection – Fundamental Differences Affecting Analytical Performance.</a><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Episode_2_The_Benefits_of_CAD_Compared_to_Other_Universal_Detectors_ELSD_and_MALS_2_1d6508e68e.jpg" alt="Thermo Fisher Scientific: Episode 2 - The Benefits of CAD Compared to Other Universal Detectors - ELSD and MALS" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Episode_2_The_Benefits_of_CAD_Compared_to_Other_Universal_Detectors_ELSD_and_MALS_2_1d6508e68e.jpg 245w," sizes="100vw" width="1918" height="1079">You can find more information on why to choose <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-benefits.html#menu3">Charged Aerosol Detection for your HPLC analysis.</a><h4>Conclusion</h4>While ELSD and MALS have their unique strengths and applications, Charged Aerosol Detection (CAD) stands out for its consistent response, high sensitivity, ease of use, versatility, and robustness. These advantages make CAD a superior choice for many HPLC applications, offering reliable and accurate detection across a wide range of analytes.As the field of analytical chemistry continues to evolve, incorporating CAD into your HPLC workflow can significantly enhance your analytical capabilities, providing deeper insights and more reliable data. Whether you are dealing with pharmaceuticals, food additives, environmental samples, or biotechnological compounds, CAD offers a powerful and versatile solution that can meet the demands of modern analytical challenges.Stay tuned for the next episode in our series, where we will explore specific case studies and practical applications of CAD in various industries.<blockquote>Visit us on LinkedIn: #CAD, #ChargedAerosolDetection #HPLCMarcus 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 2: The Benefits of CAD Compared to Other Universal Detectors: ELSD and MALS

Our Library never stops expanding. What are the most recent contributions to LabRulezLCMS Library in the week of 20th October 2025? Check out new documents from the field of liquid phase, especially HPLC and LC/MS techniques!<blockquote>👉 <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library">SEARCH THE LARGEST REPOSITORY OF DOCUMENTS ABOUT LCMS AND RELATED TECHNIQUES</a></blockquote><blockquote>👉 Need info about different analytical techniques? Peek into <a target="_blank" rel="noopener noreferrer" href="https://gcms.labrulez.com/library">LabRulezGCMS</a> or <a target="_blank" rel="noopener noreferrer" href="https://icpms.labrulez.com/library">LabRulezICPMS</a> libraries.</blockquote>This week we bring you posters by Agilent Technologies / AOAC, Shimadzu / AOAC and Thermo Fisher Scientific / HPLC Symposium and application note by Waters Corporation!<h3>1. Agilent Technologies / AOAC: Evaluating System Robustness of a High-Sensitivity Triple Quadrupole LC/MS for PFAS Analysis in Food Matrix Over an Extended Period&nbsp;</h3><ul><li>Poster</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/ps_pfas_salmon_6495d_robustness_aoac_2025_t004_en_agilent_9b7b469a22.pdf">Full PDF for download</a></li></ul>Due to the rapidly evolving regulatory environment of per- and polyfluoroalkyl substances (PFAS), many analytical laboratories are opting to use highsensitivity triple quadrupole mass spectrometers for the targeted analysis of such compounds to ensure meeting present and potential future requirements for sensitivity and PFAS coverage. These assays are regularly conducted in a high-throughput manner involving complex matrices such as food, soil, wastewater or biological samples. Therefore, system robustness and instrument uptime are crucial for such applications to maintain productivity and profitability. In this work, we present results from an expedited robustness testing of a high-sensitivity triple quadrupole LC/MS system using select PFASs in one of the most challenging food matrices.<h4>Experimental</h4><h5>Instrumentation</h5>Data was collected using an <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=Agilent+1290+Infinity+II+LC">Agilent 1290 Infinity II LC</a> system coupled to an <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=6495D+LC%2FTQ">Agilent 6495D LC/TQ mass spectrometer.</a> Instrument parameters are summarized in Tables 1 and 2.<h4>Conclusions</h4>The robustness of a 6495D LC/TQ was tested using undiluted salmon extract, a complex and challenging food matrix. During the experiment, the system was exposed to more than 130 mL of the matrix over a period of ~3 weeks of continuous operation, without any maintenance. System performance was monitored by injections of a mixture of native and isotopically labelled PFAS samples. The monitored signals exhibited low variations (RSD&lt;6%) throughout the entire experiment. No obvious performance degradation or significant contamination of the inner ion optics elements were observed after the conclusion of the test.&nbsp;Although no loss of instrument performance was observed during this expedited robustness test, a routine maintenance of ion source and optics is recommended to ensure prolonged instrument operation.<h3>2. Shimadzu / AOAC: Analysis of Chlordane by DUIS (Dual Electrospray/Atmospheric Pressure Chemical Ionization) Liquid Chromatography Mass Spectrometry&nbsp;</h3><ul><li>Poster</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/aoac_2025_w050_036db56f51.pdf">Full PDF for download</a></li></ul>The legalization of cannabis has led to many laboratories developing methods to meet local cannabis testing regulatory requirements. One of the challenging residual pesticides to quantitate is chlordane, an organochlorine compound used as a pesticide on crops until 1983 and for termite treatment in homes until 1988. Chlordane is highly persistent in the environment and has been linked to cancers. Gas chromatography mass spectrometry and atmospheric pressure chemical ionization (APCI) – liquid chromatography mass spectrometry (LCMS) methods were published for analysis of chlordane. However, for laboratories without APCI functionality or who prefer not to switch between two different ionization sources, chlordane remains a challenging target for LCMS analysis. This study demonstrates the successful quantitation of chlordane using additive-free DUIS electrospray ionization – LCMS at concentrations below the New York State testing limits.<h4>Methods&nbsp;</h4>Technical chlordane (CAS 57-74-9) was obtained from Restek, diluted in water, and analyzed on a <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=1&amp;search=LCMS-8060">Shimadzu LCMS-8060</a> triple quadrupole mass spectrometer equipped with a DUIS ionization source. The DUIS source was utilized in APCI mode. Technical chlordane is a mixture of transchlordane, cis-chlordane, and related chemicals. The LC parameters shown in Table 1 allowed separation of the cis- and trans-chlordane isomers.<h4>Results&nbsp;</h4>Initial MS data was collected in Q1 and Q3 Scan mode. Due to the 8 chlorine atoms per chlordane molecule, a distribution of isomers is expected in the mass spectrum. LabSolutions Insight Explore was used to predict isotopic distributions for chlordane with and without adducts. The predicted spectra for the [M-H]- and [M+CH3OH]- are shown in Figure 1A and 1B, respectively. The experimentally observed isotopic distributions for the [M-H]- and [M+CH3OH]- ions are shown in Figure 1C and 1D, respectively. Figure 1E shows the relative intensity of the [M+CH3OH]- versus the [M-H]- isotope clusters. As the [M+CH3OH]- showed the greatest intensity, it was selected for optimization.Voltage optimization was performed for the 441.80 to 441.80 MRM with the CID gas turned off. Even after voltage optimization, the signal-to-noise from the primary species in the technical chlordane (in this case, trans-chlordane) was insufficient. Automated source optimization using LabSolutions MRM Connect was used to improve signal by optimizing Interface Temperature, Heating Gas Flow, Nebulizing Gas Flow, Drying Gas Flow, DL Temperature, Heat Block Temperature, and Interface Voltage. As a representative example, Figure 3 shows the impact of Interface Temperature on the MRM intensity for the 441.80 m/z.<h3>3. Thermo Fisher Scientific / HPLC Symposium: HPLC transfer and optimization of deoxycholic acid analysis using HPLC – Charged Aerosol Detector</h3><ul><li>Poster</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/po_hplc_transfer_optimization_deoxycholic_acid_analysis_po_en_55bc47dc90.pdf">Full PDF for download</a></li></ul>The United States Pharmacopeial Convention monograph outlines a high-performance liquid chromatography with charged aerosol detection (HPLC-CAD) method [1] for the accurate measurement of deoxycholic acid (also known as desoxycholic acid) and its primary impurity, cholic acid. Key detector settings that influence detection performance metrics such as detection limit, resolution, and linearity include:&nbsp;<ul><li>The evaporation temperature (EvapT) for setting the temperature of the evaporation tube and influencing sensitivity related to volatility factors.&nbsp;</li><li>The filter constant for balancing noise and adjusting the detector's response time to changes in analyte concentration.&nbsp;</li><li>The PV for optimizing the linear range within the detector's dynamic range for a given application.&nbsp;</li></ul>These parameters are crucial for successful method transfer and optimization. Consequently, this work offers guidelines for method transfer and optimization from the Vanquish CAD to the Vanquish CAD HPMethods: A <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/743">Thermo Scientific Vanquish Flex UHPLC system</a> equipped with both the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/2176">Vanquish Charged Aerosol Detector </a>and HP was used to perform method transfer and optimization for deoxycholic acid analysis. Chromatographic separation was achieved using a <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/2005">Thermo Scientific Acclaim 120 C18 column</a> under gradient elution with formic acid-modified aqueous and organic phases<h5>Chromatography Data System&nbsp;</h5>The <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/76">Thermo Scientific Chromeleon 7.3.2 Chromatography Data System (CDS) software</a> was used for data acquisition and analysis.<h4>Conclusions&nbsp;</h4>This study highlights the successful optimization and method transfer of the USP-NF deoxycholic acid assay using Vanquish CAD detectors. Through careful evaluation of chromatographic performance, detector settings, and calibration parameters, the Vanquish CAD HP was shown to deliver enhanced performance across multiple criteria:&nbsp;<h5>Key Takeaways:&nbsp;</h5><ul><li>Excellent Sensitivity and Response: Vanquish CAD HP demonstrated significantly lower LOD/LOQ values and higher peak responses compared to Vanquish CAD, making it the detector of choice for low-level analyte quantification.&nbsp;</li><li>Enhanced method optimization Flexibility: Vanquish CAD HP allows simultaneous data collection for multiple PVs, ensuring faster method development and optimization.&nbsp;</li><li>Seamless Method Transfer: Transitioning from Vanquish CAD to CAD HP was achieved by optimizing power value (PV), EvapT, and signal filter settings, ensuring improved performance.&nbsp;</li></ul>Together, these findings demonstrate that the Vanquish CAD HP not only supports efficient method transfer but also elevates performance, sensitivity, and usability—making it an ideal solution for modern HPLC applications.<h3>4. Waters Corporation: Multi-Residue Analysis of Pharmaceuticals, Personal Care Products (PPCPs) and Pesticides in Water by Direct Injection Using LC-MS/MS</h3><ul><li>Application note</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/720008819_en_4c0e9bc91e.pdf">Full PDF for download</a></li></ul><h5>Benefits&nbsp;</h5><ul><li>Sensitivity of Xevo TQ Absolute allows for the trace level detection of PPCPs and pesticides in drinking and surface waters without the need for lengthy clean-up or concentration steps</li><li>The direct injection approach increases productivity and provides faster turn-around time for reporting of results while being well aligned with green analytical chemistry principles</li><li>More than 150 analytes reach limits of quantification of 10 ng/L, making this method suitable for screening for multi-class analytes in water matrices&nbsp;</li></ul>In recent years, there has been increasing concern about the presence of pesticides, pharmaceuticals and personal care products (PPCPs) in water bodies throughout the world.1 The effect of these emerging contaminants on human health and their potential impact on the environment is not yet fully understood. The updated Drinking Water Directive entered into force in January 2021 and is the EU's main law for drinking water. The Directive applies to all water, either in its original state or after treatment, intended for drinking, cooking, food preparation or other domestic purposes, regardless of its origin and whether it is supplied from a distribution network, supplied from a tanker or put into bottles or containers.2 It further protects human health thanks to updated water quality standards, in accordance with World Health Organisation (WHO) recommendations, addressing emerging pollutants, such as endocrine disruptors, and promoting a preventive, risk-based approach to reduce pollution at its source.Water bodies such as rivers, lakes and groundwaters have their status defined in the EU Water Framework Directive.3 An amendment to Directive 2013/39/EU sets environmental quality standards for hazardous substances that require monitoring in these waters. A Commission Implementing Decision4 document, 2022/1307, includes Watch List analytes with Maximum Acceptable Method Detection Limits for compounds of concern across multiple chemical classes. Numerous studies have demonstrated that PPCPs are present at parts-per-trillion (PPT) levels in rivers and streams highlighting the need for methods that are able to detect compounds at these trace levels.5-10 In addition to the low-level detection of these compounds, a major analytical challenge lies in the wide chemical diversity of chemicals of concern. Furthermore, to establish a more complete understanding of water pollution it is necessary to monitor a wide variety of types of water. This application note demonstrates the direct injection, separation and detection of PPCPs and pesticides including acidic, basic, and neutral compounds from multiple regulated analyte lists in a variety of water types.<h4>Experimental</h4><ul><li>LC system: <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/191">ACQUITY Premier</a> FTN</li><li>MS system: <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/554">Xevo TQ Absolute</a></li></ul><h4>Conclusion&nbsp;</h4>The updated EU Drinking Water and Water Framework Directives provide the regulatory framework for effective monitoring and management of water quality and include provisions for emerging contaminants. Ensuring compliance with these regulations and comprehensive coverage for an ever increasing analyte lists requires versatile, robust analytical methods and high performance LC/MS/MS systems. The direct-injection method investigated in this work is effective at detection of a wide range of PPCPs and pesticides at trace levels suitable for monitoring multiple water types for the presence of compound classes known or suspected to pose risks to human and environmental health. It further provides more rapid turn around time and greener operation than methods that rely upon high volumes of solvent and extensive sample preparation. Method performance was assessed using criteria described in ISO 21253–2:2019. The calibration characteristics, linearity, and residuals were excellent over the concentration range studied. Accuracy and precision were evaluated at three matrix QC levels with six replicate spikes and found to provide excellent performance for 154 analytes in tap and bottled water and 74 analytes in surface water matrix.

News from LabRulezLCMS Library - Week 43, 2025

The first Charged Aerosol Detector (launched in 2005) set new performance standards for near-universal detection in HPLC analysis. Now our revamped detector is here, ready to help your lab analyze complex solutions with even greater confidence.<blockquote><ul><li><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></li><li><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></li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/6249">Episode 3: Understanding How Charged Aerosol Detection (CAD) Works</a></li></ul></blockquote>Welcome to Episode 4 of our series, where we explore the latest advancements in near-universal HPLC detection technology. Today, we are excited to introduce the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/2176">Thermo Scientific Vanquish Charged Aerosol Detector P Series</a>.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Episode_4_Introducing_a_More_Confident_Era_in_HPLC_CAD_Analysis_e324503a09.jpg" alt="Thermo Fisher Scientific: Episode 4 - Introducing a More Confident Era in HPLC-CAD Analysis." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Episode_4_Introducing_a_More_Confident_Era_in_HPLC_CAD_Analysis_e324503a09.jpg 245w," sizes="100vw" width="1200" height="600">Over the past two decades, Charged Aerosol Detection has undergone significant advancements, incorporating several new hardware and software features designed to facilitate method development, increase flexibility, and streamline method transfer.This innovative detector brings unprecedented levels of sensitivity, versatility, and reliability to your laboratory, making it essential for a wide range of applications. It is the detector to use when your analyte lacks a chromophore or if a certified standard is unavailable.<h3>Key performance upgrades in the Vanquish CAD P Series</h3><h4>1. Integrated diverter valve for increased detection versatility</h4>One of the standout features of the Vanquish CAD P Series is the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_003506_hplc_vanquish_inverse_gradient_cad_polysorbate_an003506_na_en_cfd6ee0b21.pdf">integrated diverter valve</a> (Figure 1).<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Figure_1_Close_up_view_of_the_Vanquish_CAD_P_Series_integrated_diverter_valve_19bfda37ef.jpg" alt="Thermo Fisher Scientific: Figure 1. Close-up view of the Vanquish CAD P Series integrated diverter valve." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Figure_1_Close_up_view_of_the_Vanquish_CAD_P_Series_integrated_diverter_valve_19bfda37ef.jpg 245w," sizes="100vw" width="700" height="410">This valve enhances robustness by preventing detector contamination and improves peak integration by diverting the matrix to waste.This function is particularly beneficial for the accurate quantitation of early eluting analytes, ensuring cleaner and more accurate results. By reducing the risk of contamination, the diverter valve extends the detector lifespan and maintains robust performance over time.Removing unwanted matrix is especially useful in complex samples, where the risk of contamination is higher, and accurate quantitation is critical.<h4>2. New default power value settings to simplify calibration curves</h4>The Vanquish CAD P Series introduces new default power value (PV) settings, making it easier to find your ideal linear range. In case you do not know, the <a target="_blank" rel="noopener noreferrer" href="https://pubs.acs.org/doi/10.1021/acs.analchem.4c03714">power value</a> is a mathematical transformation that extends the linear range of calibration curves.Previously, determining the optimal PV for a given method was a time-consuming process, as each PV was determined sequentially. Now you can measure up to four power function values simultaneously, significantly reducing the time and effort required for method development! Collecting multiple PVs at once simplifies the process of optimizing analytical methods, ensuring accurate and reliable quantitation across a wide range of analytes.This improvement not only saves time but also enhances the overall efficiency of your laboratory workflow.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Learn_from_Chris_Tuczemskyi_about_the_power_function_in_HPLC_CAD_with_the_Polysorbate_80_example_7fc567c51a.jpg" alt="Thermo Fisher Scientific: Chris Tuczemskyi (Product Marketing Manager)" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Learn_from_Chris_Tuczemskyi_about_the_power_function_in_HPLC_CAD_with_the_Polysorbate_80_example_7fc567c51a.jpg 245w," sizes="100vw" width="800" height="400"><blockquote>Learn from Chris Tuczemskyi about the power function in HPLC-CAD with the Polysorbate 80 example. <a target="_blank" rel="noopener noreferrer" href="https://www.youtube.com/watch?v=163KV8ywYJ4">Watch on YouTube today!</a></blockquote><h4>3. Improved sensitivity for detecting and quantifying semi-volatile analytes with confidence</h4>The Vanquish CAD P Series also offers improved sensitivity for detecting and quantifying semi-volatile analytes.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Figure_2_Illustration_of_the_Vanquish_CAD_P_Series_charging_detection_module_7e5f5ccda0.jpg" alt="Thermo Fisher Scientific: Figure 2. Illustration of the Vanquish CAD P Series charging detection module." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Figure_2_Illustration_of_the_Vanquish_CAD_P_Series_charging_detection_module_7e5f5ccda0.jpg 245w," sizes="100vw" width="700" height="410">This enhancement is achieved through the new <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">Temperature Coupling Mode</a>, which supports the detection of semi-volatile compounds by fine-tuning the evaporation temperature (EvapT) and coupling with the Charging Detection Module temperature (Figure 2).For instance, setting the EvapT to 25°C with the Temperature Coupling Mode on minimizes additional evaporation of semi-volatile analytes, resulting in an improved signal-to-noise (S/N) ratio. A better S/N ratio is particularly beneficial for detecting low-level semi-volatile drug impurities and other semi-volatile compounds, providing users with a more complete profile of sample components.This increased sensitivity ensures that even the most challenging analytes can be accurately quantified, enhancing confidence in your results.<blockquote>Uncover the benefits of optimized temperature control in HPLC-CAD with Florian Broghammer. <a target="_blank" rel="noopener noreferrer" href="https://www.youtube.com/watch?v=kSuNQVcuJME">Watch the video on characterizing saturated fatty acids!</a></blockquote><h4>4. New method transfer and development tools to help you save time and master compliance</h4>The Vanquish CAD P Series includes <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/tn_003816_hplc_vanquish_method_transfer_cad_deoxycholic_acid_tn003816_na_en_1f609f0603.pdf">new method transfer and development tools</a> that streamline the process of transferring methods from previous CAD models.The built-in method translation tool ensures seamless method transfer with familiar method settings, providing a consistent user experience. This feature is particularly useful for regulated laboratories looking to upgrade their detection capabilities without extensive revalidation efforts.Additionally, the Vanquish CAD P Series supports the acquisition of data at four different power values simultaneously, simplifying method development and transfer. This capability makes it easier to optimize and validate compliant analytical methods, ensuring accurate and reliable results across various applications.The ability to transfer methods effortlessly means that laboratories can quickly adapt to new projects and demands, maintaining productivity and efficiency.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Florian_Broghammer_Product_manager_33b8ccb1a5.jpg" alt="Thermo Fisher Scientific: Florian Broghammer (Product manager)" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Florian_Broghammer_Product_manager_33b8ccb1a5.jpg 245w," sizes="100vw" width="800" height="400"><blockquote>Discover new method tools and optimized gradient HPLC-CAD for fatty acids with Florian Broghammer. <a target="_blank" rel="noopener noreferrer" href="https://www.youtube.com/watch?v=JOhYi82P1sA">Watch the video now!</a></blockquote><h4>Save time, gain confidence, and meet stringent compliance requirements</h4>The <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/cz/en/home/c/b/vanquish-charged-aerosol-detector-p-series.html">Vanquish CAD P Series</a> represents a significant advancement in analytical detection technology. Its integrated diverter valve, new default power value settings, improved sensitivity for semi-volatile analytes, and new method transfer, and development tools make it a powerful tool for a wide range of applications.Whether you are working in pharmaceuticals, biomolecules, food and beverage, or specialty chemicals, this detector provides the accuracy and reliability to achieve fast, confident, and clearer results. For more information, you can watch our on-demand webinar: “<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/webinar/5422">A Look at the Past &amp; Future Impacts of HPLC-CAD Technology</a>” with one of the technology founders to learn more details about the new advancements presented today.Stay tuned for the next episode in our series, where we will continue to explore the latest innovations in analytical technology.<h4>FAQs</h4><ol><li>How does the power value work in Charged Aerosol Detection? The <a target="_blank" rel="noopener noreferrer" href="https://pubs.acs.org/doi/10.1021/acs.analchem.4c03714">power value</a> (previously called the power function value) is just a mathematical transformation that extends the linear range of calibration curves.</li><li>What is the typical LOQ I can expect in HPLC-CAD analysis? A <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/blog/analyteguru/cad-vs-elsd-which-hplc-detector-is-your-better-option/">typical LOQ</a> for the CAD is around 1-20 ng on a column.</li><li>What compounds are compatible with the CAD? The CAD is able to detect all <a target="_blank" rel="noopener noreferrer" href="https://thermofisher.com/cz/en/home/industrial/chromatography/chromatography-learning-center/liquid-chromatography-information/hplc-system-components/how-hplc-detectors-work/charged-aerosol-detection/charged-aerosol-detection-cad-method-development-tips.html">non-volatile and many semi-volatile</a> analytes. You can now expand the range of detection for semi-volatiles with Temperature Coupling Mode in the Vanquish CAD P Series.</li></ol><blockquote>Visit us on LinkedIn: #HPLC #ChargedAerosolDetection</blockquote><blockquote>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 4: Introducing a More Confident Era in HPLC-CAD Analysis

In today’s forensic and clinical toxicology labs, productivity is more than just speed—it’s about accuracy, flexibility, and the ability to keep pace with an ever-expanding universe of analytes. Whether processing high-throughput urine samples or evaluating oral fluid, labs are under pressure to deliver reliable results faster, with fewer resources, and across a wide range of complex drug panels. Thermo Fisher Scientific is addressing this challenge head-on, delivering complete LC-MS/MS workflows, solution guides, and databases that prioritize throughput and robustness without sacrificing sensitivity or selectivity. Workflows that include over 100 to 2000 drugs allow for single injection assays that mitigate the need to extract and analyze each drug class individually. The fast speed of the mass spectrometers gives users the ability to speed up gradients, leading to shorter run times.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Boosting_Productivity_in_Toxicology_Labs_7d80cfd388.jpg" alt="Thermo Fisher Scientific: Boosting Productivity in Toxicology Labs." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Boosting_Productivity_in_Toxicology_Labs_7d80cfd388.jpg 245w," sizes="100vw" width="1024" height="512"><h3>A unified workflow for broad drug coverage in urine</h3>Urine remains the cornerstone matrix for drug testing, offering a long detection window for many commonly abused substances. However, with over 100 frequently tested drugs and a growing list of synthetic analogs, labs need streamlined methods capable of handling this analytical diversity. A recent method developed by application scientist Courtney Patterson using <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/chromatography/chromatography-sample-preparation/sample-preparation-consumables/solid-phase-extraction-consumables/sola-spe-plates-cartridges.html">Thermo Scientific SOLAµ SPE plates</a>, <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=37&amp;manufacturerItems=3&amp;search=vanquish">Thermo Scientific Vanquish UHPLC</a>, and both <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=22&amp;manufacturerItems=3&amp;search=orbitrap">Thermo Scientific HRAM Orbitrap</a> and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=20&amp;manufacturerItems=3&amp;search=tsq">Thermo Scientific TSQ triple quadrupole</a> mass spectrometry platforms, delivers a compelling solution. This workflow (linked in the resources section below), utilizes both HRAM Orbitrap and triple quadrupole mass spectrometers, quantified 106 drugs—including 15 isomers—across 10 drug classes, including drugs in both positive and negative polarities, in just 7 minutes per sample. Notably, it demonstrated strong chromatographic resolution for challenging isomeric pairs like codeine/hydrocodone and methamphetamine/phentermine. Lower limits of quantitation (LOQs) ranged from 0.1 to 100 ng/mL, meeting stringent ANSI and forensic standards. Wide dynamic ranges, such as 0.5 to 5,000 ng/mL for norbuprenorphine, enabled labs to confidently report both trace and high-concentration results with minimal rework.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Boosting_Productivity_in_Toxicology_Labs_2_0e2f7432b4.jpg" alt="Thermo Fisher Scientific: Boosting Productivity in Toxicology Labs: Figure 1 Extracted ion chromatogram of 106 drugs of abuse in urine from TN002363." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Boosting_Productivity_in_Toxicology_Labs_2_0e2f7432b4.jpg 220w," sizes="100vw" width="672" height="476">What makes this method stand out is its dual-platform compatibility. The same sample preparation and chromatography approach has been validated on both high-resolution Orbitrap and triple quadrupole systems, giving laboratories the freedom to select instrumentation that best aligns with their throughput needs and budget constraints.And speaking of budgets… Be sure to explore our latest promotions, including <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/o/b/clinical-lcms-discounts.html">complete LC-MS toxicology configurations</a> and <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/mass-spectrometry/mass-spectrometer-price-affordability-programs.html">affordability programs</a>. You can aim high without overspending by:<ul><li>Investing in certified refurbished instruments at a fraction of the cost</li><li>Trading in older instruments for credit toward the latest models, regardless of manufacturer</li><li>Taking advantage of flexible leasing and financing options, including 0% interest and deferred payment plans</li></ul><h3>Meeting new demands in oral fluid testing with Stellar MS</h3>As oral fluid gains traction for workplace drug testing, roadside evaluations, and rapid screening, labs face a different set of challenges—chief among them, the need for highly sensitive and selective methods to meet SAMHSA detection thresholds. Patterson’s oral fluid workflow, powered by the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Thermo Scientific Stellar mass spectrometer</a>, addresses these needs with precision in a 5-minute method. Using DPX Technology’s INTip™ SCX/WAX SPE tips for extraction and an<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/424"> Accucore Biphenyl column</a> for separation, this method quantified 31 drugs—including THC, opioids, stimulants, and cocaine—at LOQs as low as 0.25 ng/mL. The Stellar system’s targeted-MS2 (tMS2) acquisition mode delivered confident identification with full-scan MS2 spectra, resolving issues like matrix suppression common in oral fluid analysis.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Boosting_Productivity_in_Toxicology_Labs_3_146d0fde1c.jpg" alt="Thermo Fisher Scientific: Boosting Productivity in Toxicology Labs: Figure 2 Schematic of XTR tip extraction protocol with mixed mode SCX/WAX chemistry for INTip dispersive solid phase extraction followed by analysis using the Vanquish Horizon UHPLC system and Stellar Mass Spectrometer from TN003851. Artwork provided by DPX Technologies." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Boosting_Productivity_in_Toxicology_Labs_3_146d0fde1c.jpg 245w," sizes="100vw" width="867" height="375">Importantly, the method achieved baseline separation of structural isomers and provided flexibility in fragmentation, using either HCD or CID based on compound-specific needs. Ten real-world case study samples were analyzed successfully, confirming all compounds with robust retention times and fragment ion ratios.<h3>Productivity without compromise</h3>Together, these two workflows—one for urine and one for oral fluid—showcase how Thermo Fisher Scientific is redefining productivity in toxicology. By combining smart sample preparation, fast chromatography, and high-resolution mass spectrometry platforms, these solutions enable:<ul><li>Rapid turnaround times with sub-10-minute methods</li><li>High-confidence results for complex drug panels, including isomers</li><li>Flexible instrumentation to meet the needs of both high-resolution and triple quadrupole users</li><li>Regulatory readiness with LOQs meeting ANSI and SAMHSA guidelines</li></ul>In a world where toxicology labs must do more with less, Thermo Fisher’s comprehensive solutions empower teams to work faster, smarter, and with greater confidence.Learn more about how Thermo Fisher Scientific’s toxicology solutions can help your lab stay ahead: <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/forensics/forensic-toxicology.html">Forensic Toxicology</a><h3>Resources</h3><ul><li>Past blogs in this series<ul><li>Sample prep – <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/6189">Sample Preparation Strategies Demystified: Choosing the Right Fit for Your Toxicology Workflow</a></li><li>Tox Explorer – <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/6587">Beyond Blood: Sheffield Teaching Hospitals NHS Foundation Trust Develops HRAM-Powered Method for Post-Mortem Toxicology Analysis</a></li><li>VeriSpray – <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/6860">Advancing Drug Analysis with PaperSpray MS</a></li></ul></li><li>On-demand workshop – <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/webinar/4735">Next-Generation Workflows for Small Molecule Quantitation Using the Thermo Scientific Stellar Mass Spectrometer</a></li><li>Technical note – <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/paper/32266">Quantitation of an oral fluid drug panel including THC using the new Stellar mass spectrometer</a></li><li>Technical note – <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/paper/32265">Utilizing HRAM Orbitrap mass spectrometry to quantitate 106 drugs of abuse in urine</a></li><li>Technical note – <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/paper/32265">Utilizing triple quadrupole mass spectrometry to quantitate 106 drugs of abuse in urine</a></li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/paper/32265">Drug screening and confirmation workflows</a></li><li>Promotions<ul><li><a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/o/b/clinical-lcms-discounts.html">Save up to 40% on complete LC-MS toxicology configurations</a></li><li><a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/mass-spectrometry/mass-spectrometer-price-affordability-programs.html">Mass spectrometer affordability programs</a><ul><li>Refurbished MS</li><li>Trade-in</li><li>Financing/ leasing</li></ul></li></ul></li></ul>Visit us on&nbsp;<a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a>&nbsp;#ForensicToxicology #MassSpectrometry #LabProductivity<blockquote><h5>Ema Ruzic</h5><div>Vertical Marketing Manager, Chromatography and Mass Spectrometry Division (CMD)</div></blockquote>

Boosting Productivity in Toxicology Labs

News from LabRulezLCMS Library - Week 19, 2026

Why are switchable 2D-LC workflows fit for mAb manufacturing? Discover a practical AQbD approach for monitoring charge and size variants in one hour.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_689c6925a2.jpeg" alt="Thermo Fisher Scientific: Monitoring mAb Manufacturing the Easy Way with Switchable 2D‑LC-UV-MS." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_689c6925a2.jpeg 245w," sizes="100vw" width="1024" height="512">Lost material. Delayed production timelines. Reworks across teams.If you’re working with monoclonal antibodies (mAbs) or other biopharmaceuticals, you already know the challenge: biological reactions are variable.Unlike traditional small-molecule drugs, with simpler and more predictable chemical structures, biotherapeutics exist in a dynamic state of microheterogeneity — no two batches are ever truly identical.Whether undergoing production, processing, or storage, these compounds often undergo unwanted side reactions like glycation, deamidation, charge variation, and aggregation, which can compromise product safety and efficacy.Finding robust and dependable ways to monitor these critical quality attributes (CQA) and protect therapeutic integrity is even more pressing, as regulatory agencies demand comprehensive characterizations.While analytical techniques like liquid chromatography (LC) and mass spectrometry (MS) play a fundamental role in CQA analysis, the increasing complexity of analytical tasks is forcing the requirements of instruments to grow.The good news? <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/blog/analyteguru/biopharma-boost-how-2d-lc-went-from-expert-only-to-routine/">Targeted two-dimensional LC (2D-LC)</a> workflows that can handle analytical complexity and support straightforward method development without any manual fluidic changes are already here.Let’s explore how your lab can use 2D-LC coupled with ultraviolet detection (UVD) or high-resolution accurate mass spectrometry (<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=22&amp;manufacturerItems=3">HRAM-MS</a>) to monitor the CQAs of intact mAbs in real time (Figure 1).<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_2_8ee6b79638.jpeg" alt="Thermo Fisher Scientific: Monitoring mAb Manufacturing the Easy Way with Switchable 2D‑LC-UV-MS: Figure 1. Fluidic scheme of a 2D-LC-MS setup that supports multiple CQA analysis as well as method development without any manual replumbing." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_2_8ee6b79638.jpeg 224w," sizes="100vw" width="800" height="559"><div><h4>Key takeaways:</h4><ul><li>Why mAb variants matter</li></ul>Physiochemical modifications generate diverse mAb variants — such as deamidated and aggregated species — that require monitoring to protect therapeutic efficacy and safety.<ul><li>What switchable 2D-LC brings you</li></ul>Switchable heart-cut 2D-LC workflows allow direct upstream monitoring of multiple CQAs during the production cycle from cell culture samples.<ul><li>How the separation works</li></ul>The mAb is purified from cell culture samples by protein A (ProA) affinity in the first dimension (1D). A high-performance strong cation exchange (SCX) column applied in the second dimension (2D) facilitates the separation of mAb charge variants or serves as a trap column to focus the purified mAb fraction prior to transfer to size exclusion chromatography (SEC).<ul><li>Speed vs. depth: choosing the right detector</li></ul>UVD monitoring provides quick and simple trendlines, while the direct coupling of 2D with HRAM-MS allows deep characterizations and comprehensive insights into glycan profiles, modifications, and aggregates at the intact level.<ul><li>Why at-line monitoring matters</li></ul>Near real-time analysis of bioreactor samples enables earlier intervention, helping control material costs, improve yield, reduce off-target variants, and avoid costly downtime from rework or restarting production.</div><h3>How 2D-LC workflows help streamline mAb manufacturing and prevent costly issues</h3>Near real-time monitoring enables early intervention of issues, helping maintain product cost and quality, protect yield, and more consistent downstream performance.As best practice, you should begin monitoring product quality attributes (PQAs) from the start of the cell culture and continue daily throughout the process until your reaction reaches the target yield (Figure 2).<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_3_bb3e594d4a.jpeg" alt="Thermo Fisher Scientific: Monitoring mAb Manufacturing the Easy Way with Switchable 2D‑LC-UV-MS: Figure 2. mAb titer calibration curve (left) and titer determination of cell culture samples from 1D ProA-UV (right). Samples were drawn from the bioreactors over 10 days." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_3_bb3e594d4a.jpeg 245w," sizes="100vw" width="768" height="282">For established reactions, you can track changes in titer, charge, or size variant profiles based on UV spectral patterns quickly adjust feeds or cell harvest timing to prevent further issues during downstream processing.Trends like the formation of new shoulders, slight peak shifts, or loss in peak intensity often signal changes in media composition, nutrient availability, pH, or process stress (Figure 3).For example:<ul><li>Emerging acidic or basic species may indicate chemical modifications, like glycation, deamidation, or other stress‑related changes.</li><li>Size variants can reflect fragmentation or aggregation driven by temperature, agitation, or hold times.</li></ul><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_4_44dd018404.jpeg" alt="Thermo Fisher Scientific: Monitoring mAb Manufacturing the Easy Way with Switchable 2D‑LC-UV-MS: Figure 3. 2D chromatogram of ProA-SCX-SEC analysis of harvested cell culture samples drawn on days 2 and 9." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_4_44dd018404.jpeg 204w," sizes="100vw" width="768" height="587"><h3>Why switchable workflows provide a simpler path to fewer surprises, faster course corrections, and more consistent mAb production</h3>Fortunately,&nbsp;you&nbsp;don’t&nbsp;need a complicated,&nbsp;manual&nbsp;multistep&nbsp;analysis pipeline to keep your mAb production schedule on track. A streamlined, switchable 2D-LC-UV-MS workflow gives you fast, actionable insights—straight from the bioreactor.&nbsp;The setup includes a <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/chromatography/liquid-chromatography-lc/hplc-uhplc-systems/vanquish-simple-switch-2d-lc.html">switchable fluidic design</a> that lets you toggle between charge (SCX) and size variant analysis (SEC) without replumbing the hardware, providing complementary information.This convenient approach <a target="_blank" rel="noopener noreferrer" href="https://www.youtube.com/watch?v=xOzYpxWbvQw">combines cleanup and analysis in one system</a>, eliminating manual sample preparation and enabling direct analysis of cell culture supernatants from the bioreactor (Figure 4).<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_5_d6dc6b0059.jpeg" alt="Thermo Fisher Scientific: Monitoring mAb Manufacturing the Easy Way with Switchable 2D‑LC-UV-MS: Figure 4. Quality attribute monitoring of mAb biosynthesis by switchable 2D-LC-UV or MS workflow." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_5_d6dc6b0059.jpeg 245w," sizes="100vw" width="768" height="215"><h4>How switchable 2D-LC technology works:</h4><ul><li>1D. ProA affinity chromatography for titer determination and isolation of the mAb from host cell material and media components. The purified fraction is then sent via automated heart‑cut transfer straight into the 2D. The 1D elution conditions facilitate optimal mAb capture at the SCX column in the 2D.</li><li>ProA‑SCX to see charge drifts. Gradient elution of the SCX column in the 2D to separate acidic and basic variants from the main peak.</li><li>ProA‑SCX‑SEC to see aggregation risks. The SCX column is switched in line with the SEC column to resolve the monomer, low‑molecular‑weight (LMW), and high‑molecular‑weight (HMW) fractions. The SCX column here acts as a trap and refocusing stage, releasing the mAb into SEC in a narrow band by a step increase to high ionic strength. The trap/elute procedure is critical to yield sharp peaks downstream, as SEC cannot refocus bands, broadened by the loop volume.</li></ul>Together, these workflows support both early risk detection and informed corrective action without adding analytical complexity.<h3>UVD or MS? How to pick the right tool for the job</h3>With switchable 2D-LC workflows, you can select different detection options in the 2D: UVD or HRAM-MS (Figure 5). The fluidic setups differ slightly, but you must always use a fully volatile buffer system with the MS option.<h4>Here’s how to choose the right setup:</h4><ul><li>UVD is ideal for routine, in‑time process control of established reactions. Provides <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_004276_hplc_vanquish_heartcut_2dlc_antibody_bioproduction_processes_an004276_na_en_201cb3360f.pdf">quick and simple</a> trendlines when you need clear thresholds to act on, as well as straightforward decisions when you need day-to-day control of established processes. Like the “traffic light” for your production.</li><li>HRAM-MS is best when you need detailed native intact‑level confirmation, glycoform profiling, or deeper characterization of modifications <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_003310_hplc_vanquish_2dlc_quality_attributes_mabs_an003310_na_en_8caddf8c25.pdf">during the development stage</a> (Figure 5).</li></ul><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_6_d039a60ac0.jpeg" alt="Thermo Fisher Scientific: Monitoring mAb Manufacturing the Easy Way with Switchable 2D‑LC-UV-MS: Figure 5. Coupling to UVD or HRAM MS in 2D charge variant analysis. Left: quick and straightforward batch comparison with the ProA-SCX-UV. Right: ProA-SCX-HRAM MS provides deep insights into glycoforms and modifications at the intact mass level." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_6_d039a60ac0.jpeg 245w," sizes="100vw" width="768" height="232"><h3>Operational benefits your entire team can trust</h3>Real-time monitoring of mAb CQAs reveals when you need to intervene and implement a bioprocess change, protecting you from the most expensive surprises: scrap costs, poor yield, off-target product, and the downtime it takes to clean and start over.From an operations perspective, the benefits of switchable 2D-LC workflows are clear and practical (Figure 6).<ul><li>A single system performs at-line cleanup and analysis, reducing manual handling and process variability.</li><li>Heart-cut transfer minimizes sample loss and contamination risk, while the switchable design provides fit-for-purpose flexibility and delivers comprehensive insight into charge and size variants within one hour.</li><li>Regular daily sampling of crude cell culture supernatants directly from the bioreactor builds reliable trendlines over time.</li><li>Operators can quickly identify batch-divergent behavior using UVD to support timely process adjustments or perform deeper molecular characterization with HRAM MS.</li><li>A standardized, switchable workflow also supports method transfer across teams and sites, reducing variability during scale-up and method transfer.</li></ul>Fewer surprises, faster course corrections, and scaling operations without expert guidance are something analysts, engineers, quality control, finance, and regulatory bodies can all get behind.<h5>Interested in using switchable 2D-LC workflows for your mAb manufacturing processes?</h5>See real bioreactor data and step-by-step setup details in our application notes today.<ul><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_004276_hplc_vanquish_heartcut_2dlc_antibody_bioproduction_processes_an004276_na_en_201cb3360f.pdf">Switchable 2D-LC-UV workflows for routine monitoring</a></li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_003310_hplc_vanquish_2dlc_quality_attributes_mabs_an003310_na_en_8caddf8c25.pdf">Switchable 2D-LC-MS workflows for deeper characterizations</a></li></ul><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_7_d8882ed8ae.jpeg" alt="Thermo Fisher Scientific: Monitoring mAb Manufacturing the Easy Way with Switchable 2D‑LC-UV-MS: Figure 6. Illustration showing how switchable 2D-LC works." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Monitoring_m_Ab_Manufacturing_the_Easy_Way_with_Switchable_2_D_LC_UV_MS_7_d8882ed8ae.jpeg 245w," sizes="100vw" width="768" height="384"><h3>Frequently asked questions</h3><div><div><h5>1. What mAB quality control attributes should I monitor my reaction for regulatory?</h5>Some of the most important critical quality attributes of cell culture derived samples you should monitor include mAb titer, charge and size variants, and glycosylation profiles.</div><div><h5>2. What is 2D-LC?</h5>2D-LC&nbsp;is a technique that successively uses two complementary LC modes for a multi-dimensional separation. Traditionally such systems are used for additional selectivity to help resolve complex separations or to deplete interfering matrices.</div><div><h5>3. What is the benefit of using a switchable 2D-LC workflow for mAb manufacturing?</h5>Switchable heart-cut 2D-LC workflows facilitate toggling&nbsp;between size and charge variant&nbsp;analysis of the intact mAb under native conditions — directly from cell culture samples — without reconfiguring&nbsp;the&nbsp;hardware.</div><div><h5>4. Should I use UVD or MS during mAb manufacturing?</h5>UVD supports quick, efficient decisions during production progression and is ideal for monitoring well-established biosynthetic processes. HRAM-MS allows for a deep characterization and comprehensive insights into glycan profiles, modifications, and aggregates at the intact level.</div></div><blockquote>Visit us on&nbsp;<a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a>&nbsp;#ChargeVariantAnalysis, #HRAM, #LiquidChromatography</blockquote>

Monitoring mAb Manufacturing the Easy Way with Switchable 2D‑LC-UV-MS

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