Our Library never stops expanding. What are the most recent contributions to LabRulezLCMS Library in the week of 25th August 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 poster by Agilent Technologies / ASMS, brochure by Shimadzu, other document by Thermo Fisher Scientific and application note by Waters Corporation!<h3>1. Agilent Technologies / ASMS: Highly Sensitive Quantitation of N-Nitroso Timolol Impurity in Timolol API using the Agilent <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=6495D+LC%2FTQ">6495D LC/TQ</a></h3><ul><li>Poster</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/ps_6495d_nitrosamines_asms_2025_mp_548_en_agilent_7c9b0b32ef.pdf">Full PDF for download</a></li></ul>Nitrosamines are of concern as most of them have been reported to be potent mutagens in rodents and are potential carcinogens. Therefore, it is important to control these impurities at or below the stipulated specification limits. API-derived complex nitrosamines are known as nitrosamine drug substance-related impurities (NDSRIs). Multiple recalls of pharmaceutical drug products due to the presence of NDSRIs have drawn the attention of regulators and manufacturers. By considering the complexity of the global pharmaceutical supply chain, manufacturers must be more diligent to protect consumers by screening their APIs and drug products for the presence of NDSRIs. NDSRIs can be formed from both secondary and tertiary amines. Secondary amines can easily undergo nitrosation in the presence of trace amounts of acid. Timolol is beta-blocker class of drug used for hypertension. N-nitroso timolol is an API specific nitrosamine impurity. For most NDSRIs, analytical methods are not yet available, so manufacturers will need to develop, qualify, and validate a method that is suitable for the sample matrix and specific for the nitrosamines in question.The analytical method developed must be sensitive enough to quantify the nitrosamines of interest down to a level that corresponds to 10% of specification limit.In this poster we highlight a highly specific, sensitive, and reproducible method that was developed for the quantitation of N-nitroso Timolol impurity in Timolol drug substance using the 6495D triple quadrupole LC/MS (LC/TQ) coupled to the 1290 Infinity II LC.<h4>Experimental</h4><h5>LC configurations and parameters:</h5><ul><li>Instrument: <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=6495D+LC%2FTQ">Agilent 6495D LC/TQ</a> coupled to <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=10&amp;search=1290+Infinity+II+LC">1290 Infinity II LC</a></li><li>Analytical Column: Agilent Infinity Lab Poroshell PhenylHexyl, 150 × 3.0 mm, 2.7 µm, p/n, 693975-312</li></ul><h4>Conclusions</h4>A highly sensitive and robust multiple reaction monitoring (MRM) method was developed utilizing the Agilent 6495D LC/TQ to quantify N-nitroso timolol impurity in timolol API. &nbsp;<ul><li>The chromatographic method provided desirable separation between the impurity and the API to avoid interference.&nbsp;</li><li>The developed method demonstrated excellent linearity over the range of 5 to 1500 pg/mL (0.5 to 150 ppb with 100 mg/mL API load) with an R2 value greater than 0.9990&nbsp;</li><li>The LOD and LOQ values achieved were 2 and 5 pg/mL respectively for targeted NDSRI&nbsp;</li><li>The method provided recovery between 90 and 110%, which is within the acceptance criteria</li></ul><h3>2. Shimadzu: Liquid Chromatograph Mass Spectrometer <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=1&amp;search=LCMS-8065XE">LCMS-8065XE&nbsp;</a></h3><ul><li>Brochure</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/c146_e500_526bbea8e9.pdf">Full PDF for download</a></li></ul><h5>Shimadzu LCMS-8065XE: Next-Generation Triple-Quadrupole Performance</h5>Shimadzu introduces the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=1&amp;search=LCMS-8065XE">LCMS-8065XE</a>, a triple-quadrupole liquid chromatograph mass spectrometer designed to set new standards in sensitivity, speed, and robustness. Built on Shimadzu’s philosophy of “Contributing to Society Through Science and Technology,” the system integrates advanced hardware with Analytical Intelligence software, ensuring both expert-level optimization and user-friendly operation. This balance of evolved, efficient, and exact capabilities makes the LCMS-8065XE a powerful solution for modern laboratories.<h5>Breakthrough Ionization and Detection Technologies</h5>At the heart of the system are innovations such as the StreamFocus ESI probe and IonFocus technology, which enhance ion intake, reduce gas consumption, and eliminate contamination without compromising sensitivity. Combined with the refined UFsweeper IV collision cell, the instrument achieves exceptional signal transmission and robust long-term stability. Demonstrated by ultra-trace PFAS detection at parts-per-trillion levels, the LCMS-8065XE ensures reliable results even under continuous high-throughput conditions.<h5>Ultra-Fast Mass Spectrometry with UF Technologies</h5>Shimadzu’s proprietary UF technologies—including UF-Qarray II, UF-Lens II, and UF-MRM—deliver unmatched speed and sensitivity. Capable of 5 msec polarity switching, up to 555 MRM channels per second, and scanning at 30,000 u/sec, the system supports complex multi-component analyses with precision. Intelligent maintenance features, such as quick desolvation line replacement without breaking vacuum, further minimize downtime and maximize laboratory productivity.<h5>Smart Software, Sustainability, and Seamless Integration</h5>The LCMS-8065XE is complemented by Peakintelligence AI algorithms, LabSolutions Connect MRM, and LabSolutions Insight, enabling automated tuning, optimized methods, and reliable peak integration with reduced manual review time. Sustainability is also central: ecology mode reduces power consumption by up to 31%, while integration with Shimadzu’s Nexera UHPLC system improves throughput and reduces resource use. Features like FlowPilot smart flow control and automatic bubble detection ensure uninterrupted performance, extending system and column lifetimes while cutting operational costs.<h3>3. Thermo Fisher Scientific: Accucore columns Resolve all your impurities without feeling the pressure</h3><ul><li>Other document</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/fl_002099_ccs_lc_columns_accucore_C18_HILIC_phenyl_fl002099_na_en_db7abbabd7.pdf">Full PDF for download</a></li></ul><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=48&amp;manufacturerItems=3&amp;search=accucore">Thermo Scientific™ Accucore™ columns </a>bring UHPLC-level performance to both HPLC and UHPLC systems, even when pressure capabilities are limited. With 14 distinct chemistries, they provide an extensive toolbox for successful method development and robust method transfer. Built on decades of innovation in stationary phase design, Accucore columns ensure reliable performance across diverse analytical challenges.<h5>Comprehensive Chemistry Portfolio for Any Separation Need</h5>The Accucore family includes multiple column chemistries tailored to different selectivity requirements. Hydrophobic options like <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/427">C18</a>, <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/428">C8</a>, and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1990">C4</a> deliver classic reversed-phase separations, while polar-modified C18 (<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/430">Polar Premium</a>, <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/429">aQ</a>) enhances retention of acidic and basic compounds. Phenyl-based phases such as <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/424">Biphenyl</a>, <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/431">Phenyl-Hexyl</a>, and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1985">PFP</a> provide orthogonal selectivity for aromatic and polar analytes, and specialty hydrophobic columns (<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/426">RP-MS</a>, <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1988">C30</a>) expand capabilities for structural isomer separation. For highly polar compounds, <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1987">HILIC</a> and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1989">Amide-HILIC</a> chemistries enable reliable retention and resolution.<h5>Optimized for Speed, Sensitivity, and Versatility</h5>Engineered with advanced particle design, Accucore columns offer rapid separations with high resolution and reproducibility. Their versatility makes them suitable for a wide range of applications, from pharmaceutical impurity profiling to food and environmental analysis. By offering both routine and specialty phases, the columns allow analysts to fine-tune selectivity and maximize productivity without compromising robustness.<h5>Trusted Innovation and Seamless Integration</h5>As part of Thermo Fisher Scientific’s portfolio, Accucore columns are backed by extensive expertise in HPLC method development and transfer. Their design supports high-throughput workflows, smooth integration into existing systems, and consistent results across laboratories. Whether the need is for routine testing or complex separations, Accucore columns deliver dependable performance with the flexibility to resolve impurities efficiently and confidently.<h3>4. Waters Corporation: Temperature Control Using Waters LC Purification Systems with Timberline's Column and Mobile Phase Heaters: Optimizing Preparative Performance&nbsp;</h3><ul><li>Application note</li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/720008874_en_6514d1a04e.pdf">Full PDF for download</a></li></ul><h4>Benefits&nbsp;</h4><ul><li>Minimizing method redevelopment at the prep scale improves process efficiency and reproducibility, ensuring predictable and reliable outcomes for isolating small and large molecules, such as oligonucleotides and peptides.&nbsp;</li><li>Elevated temperature reduces system backpressure and enables one to consider using of sub-5 µm Waters™ preparative Optimum Bed Density (OBD™) columns to increase productivity through faster separations, increased loading capacity, lower solvent consumption, shorter fraction dry-down times, and reduced waste disposal costs.&nbsp;</li><li>Enabling the substitution of acetonitrile with methanol provides a more environmentally sustainable and economically efficient purification process.</li></ul>Although temperature control is widely implemented in analytical HPLC to improve separations and ensure consistent and reliable outcomes, temperature is seldom controlled or used as a parameter for manipulating chromatography at the preparative scale for two reasons. First, high flow rate separations occur at the temperature of the incoming solvent and efficient heating of the mobile phase entering the column is challenging at these high flow rates. Second, large diameter columns cannot be effectively heated from the outside simply by using insulation, heated blankets or ovens. Ideally, analytical separations developed with temperature control should be scaled to prep at the same temperature to eliminate variability in the chromatography which can make the target identification and isolation ambiguous or lead to product loss.&nbsp;When used with the Waters AutoPurification System, Timberline’s column and mobile phase heaters provide precise and consistent temperature control for preparative separations, allowing easier scale-up from UPLC/UHPLC to preparative methods. This integrated approach minimizes the need for method redevelopment, improves reproducibility, enhances hydrophobic compound solubility and boosts operational efficiency, which is particularly valuable in small molecule isolations and biological applications such as oligonucleotide and peptide purification. Temperature control also enhances flexibility in purification workflows, supporting green chemistry initiatives by enabling the substitution of acetonitrile with methanol. Elevated temperature reduces system backpressure, allowing the usage of sub-5 µm particles in larger-dimension preparative columns (e.g., 10 mm ID), which may increase loading capacity, minimize run-times, reduce solvent consumption, shorten dry-down times and lower waste disposal costs. This technical brief illustrates that comparable purification results can be achieved using methanol with sub-5 µm 10 mm ID columns, an approach that is both environmentally sustainable and economically viable. It also illustrates the precision and stability of temperature control across various flow rates and mobile phase compositions, showcasing the reliability of this solution.<h4>Conclusion&nbsp;</h4><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/library?mainauthorItems=5&amp;search=Timberline%E2%80%99s+TL-105+D+column">Timberline’s TL-105 D column</a> oven configured with the Waters AutoPurification System provides precise and consistent temperature control when scaling from analytical to preparative methods. This significantly reduces the need for method redevelopment at the prep scale, enhances chromatographic efficiency and reproducibility and delivers predictable and reliable outcomes for various applications including small and large molecules such as oligonucleotides and peptides isolations.This combined solution supports the growing demand for green chemistry by enabling the substitution of acetonitrile with methanol. Enhanced temperature control also lowers system backpressure, allowing the use of smaller particle size, larger dimension Waters preparative OBD columns. This results in faster separations, increased loading capacity, reduced solvent consumption, shorter fraction dry-down times, and lower waste disposal costs. These benefits contribute to a more environmentally sustainable and economically efficient purification process.

News from LabRulezLCMS Library - Week 35, 2025

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

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

This study compared LC-HRMS with immunoassay (IA) for urine drug screening in an inpatient addiction unit. LC-HRMS demonstrated superior detection for two-thirds of all molecules, including many substances missed by IA despite being part of its target panel. Among 154 patients, physicians reported that LC-HRMS findings would have changed clinical management for one in four cases.A history of opioid use was the strongest predictor of clinical benefit. These results highlight the added diagnostic value of LC-HRMS for patients with complex or multiple substance use, supporting its implementation in addiction-care settings.<blockquote><h4>The original article</h4><h4><a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192">Enhancing addiction care: Benefits of urinary screening with LC-HRMS (liquid chromatography-high resolution mass spectrometry) for psychoactive substances and drugs</a></h4>Edouard Le Carpentier, Morgane Helesbeux, Vanessa Biering, Aurélie Aquizerate, Morgane Rousselet, Malcolm Barrangou-Poueys-Darlas, Audrey Verholleman, Eric Dailly, Matthieu Grégoire, Caroline Victorri-Vigneau, Mélanie DuvalProgress in Neuro-Psychopharmacology and Biological Psychiatry Volume 141, 2025, 111465<a target="_blank" rel="noopener noreferrer" href="https://doi.org/10.1016/j.pnpbp.2025.111465">https://doi.org/10.1016/j.pnpbp.2025.111465</a><h6>licensed under <a target="_blank" rel="noopener noreferrer" href="https://creativecommons.org/licenses/by/4.0/">CC-BY 4.0</a></h6></blockquote>Selected sections from the article follow. Formats and hyperlinks were adapted from the original.The Nantes University Hospital has a full-time inpatient addiction unit dedicated to the management of patients with substance use disorders. This type of hospitalisation offers patients a temporary break from the substance(s) of abuse and environmental factors, enabling them to refocus on their own personal functioning and helping to restore their physical health. These patients receive comprehensive care, combining a psychological, biological and social approach. The objectives of the hospitalisation are set out in advance in an individualized care contract. As part of this care contract, a targeted urinary drug screening is carried out systematically at the start of hospitalisation. The results of this screening can be used as a support for discussions between patients and caregivers, and may lead caregivers to redefine the objectives of care. It is therefore important that the method used for urinary drug screening is reliable, as an error in detection can have significant consequences for care and the patient-caregiver relationship.Immunoassay (Roche diagnostic®) is used at Nantes University Hospital to perform urine drug screening for the inpatient addiction unit. Although this method has a number of strengths, such as ease of sample handling and automation for rapid results, it has a number of limitations (<a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0090">Schütz et al., 2006</a>). This method is used to detect 7 pharmacological categories of psychoactive substances (some opiates, benzodiazepines, amphetamines, cocaine, buprenorphine, methadone and cannabis) without giving details of the molecule that made the test positive. Moreover, some molecules such as tramadol, zolpidem, zopiclone and cannabidiol (CBD) do not make the test positive for opiates, benzodiazepines and cannabis respectively and are therefore not detectable by the immunoassay drug screen test. The scope of substances detectable by the immunoassay is therefore limited in comparison with all the psychoactive substances consumed by the patients. In addition, this method has a significant rate of false-negative and false-positive results, particularly for amphetamines (<a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0070">Pope et al., 2023</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0080">Saitman et al., 2014</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0055">Mina, 2020</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0060">Możdżeń, 2023</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0015">Battini et al., 2023</a>), with potentially harmful consequences for patient management and the therapeutic alliance between carers and patients. It therefore seems necessary to consider the use of another method for urinary drug screening that is both more effective and offers a wider range of detectable substances. This would also make it possible to identify new substances in circulation and to detect the misuse of drugs, whether prescribed or not.The method evaluated in this study, is a drug screening technique performed by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) (ThermoFisher Scientific®), already in use at the Nantes University Hospital and other establishments in fields such as emergency medicine and forensic medicine (<a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0035">Helfer et al., 2015</a>). This method, which is more sensitive and specific than the immunoassay, has a number of valuable assets for the management of addiction patients. Its value in psychiatry and addiction medicine has been demonstrated in several studies, particularly in the management of patients with opiate use disorders (<a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0050">Marchei et al., 2021</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0100">Sundström et al., 2016</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0030">Heikman et al., 2016</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0040">La Maida et al., 2024</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0110">Virmani et al., 2023</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0005">Alías-Ferri et al., 2022</a>). Unlike immunoassay, it can be used to precisely identify the substances found in urine samples. It also has the major advantage of being able to detect all substances, including new psychoactive substances (NPS), as long as their mass spectra have been previously recorded in the LC-HRMS library. To date, around 1540 molecules can be detected by LC-HRMS at the Nantes University Hospital. However, the need to prepare samples beforehand and to analyze them in subgroups increases the time taken to deliver results compared with urine drug screening immunoassay.Before considering the implementation of urine drug screening by LC-HRMS in an inpatient addiction unit, it is necessary to ensure that the benefit of this method over immunoassay is real and significant. Several studies have compared the analytical results of immunoassays and liquid chromatography-mass spectrometry methods for the detection of substances in patients with substance use disorders (<a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0055">Mina, 2020</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0095">Sundström et al., 2015</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0020">Gerona and French, 2022</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0075">Rossi et al., 2021</a>; <a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0105">Tolan et al., 2024</a>), but none have looked at the impact of these results on the management of these patients. Knowing that a substance detection error has occurred could change the overall management of these patients, from both an addictive and a physical point of view.The primary objective of this study was therefore to evaluate the overall benefit (analytical and clinical) of the LC-HRMS urinary screening method compared with the immunoassay targeted urinary screening method in the management of patients hospitalised on an addiction unit. The secondary objective was to identify the profiles of patients for whom the use of the LC-HRMS method had a clinical benefit on their overall management.<h4>2. Method</h4><h5>2.2.2. LC-HRMS toxicological screening</h5>LC analyses were performed using a Transcend II TLX-1 and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=37&amp;manufacturerItems=3&amp;search=vanquish">Vanquish systems</a> in patients'urine. Data were acquired on an <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=37&amp;manufacturerItems=3&amp;search=vanquish">Exploris 120 Orbitrap Mass spectrometer</a> and processed with <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/77">TraceFinder 5.1 software</a> (ThermoFisher Scientific®, San Jose, USA). The gradient elution was performed on a <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/431">Thermo scientific Accucore™ Phenyl Hexyl</a> (100&nbsp;mm&nbsp;×&nbsp;2.1&nbsp;mm; 2.6&nbsp;μm). Column temperature was sat at 40&nbsp;°C. The mobile phases consisted of 2&nbsp;mM aqueous ammonium formate plus 0.1&nbsp;% formic acid (eluent A) and 2&nbsp;mM aqueous ammonium formate with acetonitrile:methanol (50:50, v/v; 1&nbsp;% water) plus 0.1&nbsp;% formic acid (eluent B). The flow rate was set to 0.5&nbsp;mL/min. The gradient was programmed as follows: 0 to1.42&nbsp;min at 99&nbsp;% A, 1.42 to 10.42&nbsp;min to 1&nbsp;% A, 10.42 to 11.92&nbsp;min to 0&nbsp;% A, 11.92 to 12.75 to 99&nbsp;% A, 12.72e15 min at 99&nbsp;% A.The Exploris 120 system was equipped with a heated electrospray ionization (HESI) source. The instrument was used in positive/negative switching ionization mode with full scan (FS) and a subsequent data dependent acquisition (DDA) mode. Mass calibration was done according to the manufacturer's recommendations using external mass calibration in the mass range of m/z 150–2000. The scan rate was up to 7.5&nbsp;Hz at a resolution of 30,000. The settings for FS were as follows: resolution, 30,000; automatic gain control (AGC) target, standard; maximum injection time (IT), automatic; and scan range, m/z 70–1000. For general screening (GS), high energy collisional dissociation (HCD) experiments were performed on the three most intense precursor ions selected from FS using DDA with an inclusion list of the ions to select for fragmentation. The three most intense precursor ions were transferred to an exclusion list for 3&nbsp;s (dynamic exclusion). The remaining settings for DDA mode were as follows: resolution, 15,500; AGC target, standard; maximum IT, automatic; isolation window, m/z 2.0, HCD 18.7, 37.5, and 56.3&nbsp;%; spectrum data type, profile.<h4>3. Results</h4><h5>3.4. Evaluation of the potential clinical benefit of the LC-HRMS screening method on the overall management of patients hospitalised in an addiction unit</h5>For a quarter of the patients (n&nbsp;=&nbsp;42, 27&nbsp;%), the addiction physicians considered that the new results provided by the LC-HRMS screening method would have had an impact on the overall management of their patients. For almost all of these 42 patients, it was the better performance of LC-HRMS in detecting a non-prescribed molecule that prompted the addiction physicians' decision. In general, the potential clinical benefit of the new data provided by LC-HRMS was influenced by whether or not the patient reported recent use of the substance under consideration. Thus, if a non-prescribed molecule was not detected by the immunoassay whereas it was detected by the LC-HRMS, but its use had been reported by the patient, the results provided by the LC-HRMS were not considered to have any impact on patient management.In addition, for only one patient, the better performance of the LC-HRMS over the immunoassay in detecting a prescribed drug justified the choice made by the addiction physicians. This was a patient dependent on oxycodone hospitalised in the addiction unit for withdrawal from this substance. Oxycodone is a synthetic molecule that cannot be detected by the immunoassay method; monitoring the patient's use of this drug during hospitalisation using the LC-HRMS screening method was considered to be decisive for the management of the patient by the addiction physicians.<h5>3.5. Identification of the profiles of patients for whom urine screening by LC-HRMS would have had a clinical benefit</h5>The comparison of the characteristics of patients for whom the LC-HRMS screening method would have had an impact on their overall management with those for whom LC-HRMS would not have had an impact (bivariate analysis) is detailed in Appendix (Table S5). Patients for whom the new results provided by LC-HRMS would have had an impact on their management were significantly more likely to have a history of opiate abuse/dependence (52&nbsp;% vs. 31&nbsp;%, p&nbsp;=&nbsp;.013) and reported recent opiate use significantly more often (24&nbsp;% vs. 10&nbsp;%, p&nbsp;=&nbsp;.026).<div>After adjusting for factors associated with a clinical benefit of the LC-HRMS screening method with a p-value &lt;.20 in the bivariate analysis, one factor was identified in the multivariate analysis (<a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#t0025">Table 5</a>): a history of opiate abuse/dependence (adjusted Od-Ratio (aOR): 2.49 [1.21–5.20]).<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Progress_in_Neuro_Psychopharmacology_and_Biological_Psychiatry_Volume_141_2025_111465_Table_5_Identification_of_the_profiles_of_patients_5e9ee502e8.jpg" alt="Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume 141, 2025, 111465: Table 5. Identification of the profiles of patients for whom urine screening by LC-HRMS would have had a clinical benefit – Multivariate analysis." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Progress_in_Neuro_Psychopharmacology_and_Biological_Psychiatry_Volume_141_2025_111465_Table_5_Identification_of_the_profiles_of_patients_5e9ee502e8.jpg 192w," sizes="100vw" width="775" height="631"></div><h4>4. Discussion</h4><h5>4.1. Main results</h5>In this study, toxicological screening by LC- HRMS had higher analytical performance than drug screen test by immunoassay for the detection and identification of around 2/3 of the drugs and substances analyzed. Its implementation in the follow-up of patients hospitalised in addiction units has been assessed by addiction physicians as having a potential impact on their management for 1/4 of the patients included in this study. Moreover, statistical analysis showed that LC-HRMS toxicological screening was of preferential benefit to patients with a history of opiate abuse/dependence.<h5>4.2. Analytical benefit of the LC-HRMS screening method</h5>In our study, we observed that the LC-HRMS and immunoassay methods produced different results. Most often, the molecule was identified by LC-HRMS but not by the immunoassay. The known deficiencies of the immunoassay led previous laboratory to investigate the feasibility of using LC-HRMS in post-mortem urine samples (<a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0095">Sundström et al., 2015</a>). It showed a clear superiority in compound-identification over immunoassays (<a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0095">Sundström et al., 2015</a>). So in this context we expected same results concerning analytical benefit of our LC-HRMS method.The differences between the LC-HRMS LOI and the immunoassay cut-off values can explain these variations. Immunoassay cut-off values are high to avoid the risk of false positive results. For instance, for cocaine, the cut-off value is 300&nbsp;ng/mL of benzoylecgonine (BEG), a cocaine metabolite, whereas LC-HRMS can identify BEG from a concentration of 0.5&nbsp;ng/mL. Another example, the immunoassay requires diazepam and its metabolites to trigger a reaction greater than or equal to 300&nbsp;ng/mL of nordazepam to yield a positive result. Among those metabolites oxazepam, temazepam and their conjugates oxazepam and temazepam glucuronide (OG and TG) had a bad cross-reactivity. On other hand, LC-HRMS can identify diazepam and its metabolites at much lower thresholds, from 1 to 10&nbsp;ng/mL. Diazepam and metabolites concentrations in urine after a single dose are often low (<a target="_blank" rel="noopener noreferrer" href="https://www.sciencedirect.com/science/article/pii/S0278584625002192#bb0115">Wang et al., 2022</a>). As their time to maximum concentration is different, in the case of a patient beginning a treatment by diazepam, the initial low concentrations in urine and the weak cross-reactivity of some metabolite could lead to an insufficient reaction and a false-negative results. This could explain the difference between the two methods, in the case of patients with a long-standing use or who have recently started treatment.<h4>5. Conclusion</h4>Urine toxicology screening using LC-HRMS is a high-performance tool, whose sensitivity and wide compound identification range may be of interest to addiction physicians in the management of their patients. The use of this urine screening method seems particularly useful in patients with multiple substance use, especially those with a history of opioid use.

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