Clinical mass spectrometry:

End-to-end solutions for toxicology, diagnostics, and beyond

Liquid chromatography-mass spectrometry (LC-MS) is increasingly used in clinical labs, with advancements in the last decade expanding its applications from inborn error detection and hormone analysis to include toxicology, drug monitoring, and disease diagnosis. MS-based tests overcome many limitations of conventional immunoassays, offering higher specificity, consistent cross-reactivity, and better detection limits. LC-MS allows for simultaneous screening of multiple compounds and enables researchers to create new tests independently, without relying on diagnostic providers.

Nevertheless, implementing LC-MS technology has its challenges, such as its complexity, limited automation, and slow sample processing. Read on to explore how to overcome these issues with Thermo Fisher Scientific's advanced instruments, automated tools, and user-friendly software. Explore streamlined workflows for fast compound analysis, see how surgeons use MS for rapid cancer detection, and learn about lab-developed test solutions through success stories from clinical mass spectrometry experts.


From sports anti-doping and workplace testing to clinical toxicology and forensic analysis, LC-MS has emerged as an invaluable tool for detecting a wide range of both known and unknown drugs and toxic substances within biological samples. Among the key challenges facing most toxicology labs today is the need to detect a ever-increasing number of substances at ever-decreasing concentrations. A pressing example is the growing opioid crisis, which has placed a demand upon testing not only for the abuse of prescription drugs but also for synthetic opioids, such as illicitly manufactured fentanyl. Expanding the scope of toxicology testing within hospital, commercial, forensic, and public health laboratories is critical to improving the surveillance of opioid use and overdoses and guiding the development of targeted prevention strategies. Below, discover how Thermo Scientific's innovative sample preparation platforms and all-in-one workflows are effectively addressing the current and emerging needs of toxicology testing.

Rapid MS tools help researchers tackle the opioid overdose crisis

The Applied Environmental Research Laboratories (AERL) at Vancouver Island University, Canada, conducts pure and applied research in analytical mass spectrometry to measure chemical determinants of environmental and human health. In the interview below, learn how the team is performing the rapid analysis of illegal drug content using Thermo Scientific™ TSQ Fortis™ Plus and Thermo Scientific™ TSQ Altis™ Plus triple quadrupole mass spectrometers with the Thermo Scientific™ VeriSpray™ PaperSpray ion source.

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The AERL team desired new technology that would allow them to set up a street-level drug-testing program, HarmCheck, to quickly identify dangerous substances such as fentanyl and carfentanil in street drugs. The resulting solution, based on the Thermo Scientific VeriSpray PaperSpray ion source connected to the Thermo Scientific TSQ Fortis Plus MS, can detect tiny quantities of street drugs and, within two minutes, provide a readout of exactly what the sample contains, including identifying dangerous opioids. To find out more, read the full story highlighted in this case study.

Thanks to the new VeriSpray system, we’re now able to better monitor the evolving illicit drug situation and further protect people who use drugs (PWUD) from preventable harm.

Professor Chris Gill, Co-director of AERL, Vancouver Island University

Featured technology: VeriSpray PaperSpray ion source

Improve turnaround time, reduce cost per test, and minimize sample preparation with the VeriSpray PaperSpray ion source, a fully automated, high-throughput, direct ionization technique used with the latest Thermo Scientific TSQ triple quadrupole mass spectrometers.

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Overdoses involving opioids killed more than 80,000 people in 2021, and nearly 88% of those deaths involved synthetic opioids, including fentanyl. To address the need to detect and identify emerging opioids, the Centers for Disease Control and Prevention (CDC), in collaboration with Cerilliant Corporation, has released Traceable Opioid Material® Kits (TOM Kits®) – reference standards to aid the confirmation of fentanyl compounds, synthetic opioids, and other emerging drugs of concern. In this technical note, explore a method for quantitation of 22 TOM Kit® fentanyl analog compounds in urine developed on the Thermo Scientific™ Vanquish™ HPLC system and Thermo Scientific™ TSQ Altis™ triple quadrupole mass spectrometer.

Additional resources
  • Screening and semi-quantitation: Comprehensive analysis of 212 fentanyl analog compounds
  • Quantitation of 22 fentanyl analog compounds on an Orbitrap Exploris 120 mass spectrometer

Leverage an all-in-one toxicology solution with Tox Explorer

The Thermo Scientific™ Tox Explorer™ collection provides an all-in-one workflow that combines efficient liquid chromatography with the latest mass spectrometry technologies to enable the detection and quantitation of a large panel of analytes in a single automated run.

In this workshop, presented at the 2022 Society of Forensic Toxicologists (SOFT) event in Cleveland, Ohio, applications specialist Kristine Van Natta reveals the evolution of the Tox Explorer Collection, an all-in-one LC-MS/MS solution that combines UHPLC and mass spectrometry technology with a growing library of more than 2100 compounds for screening and quantitation.

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Choose from two LC-MS platforms

The Tox Explorer Collection is now available with Thermo Scientific™ Orbitrap™ Exploris™ 120 and Thermo Scientific™ TSQ Quantis™ Plus triple quadrupole mass spectrometer options.

Discover the HRAM option with the Orbitrap Exploris 120, offering robust, reliable, and reproducible screening and quantitation of over 1,800 drugs of abuse in biological matrices.

Both MS options are complemented by Thermo Scientific™ TraceFinder™ software, facilitating rapid data acquisition, processing, and customized reporting, along with target analyte screening – all in one platform.

Additional resources
  • Testing for drugs of abuse in human blood to ANSI™/ASB™120 standards by high-resolution, accurate-mass mass     spectrometry
  • Detection of an expanded SAMHSA pre-employment panel by LC-MS
  • Quantitation of 106 drugs in urine using a fast 7-minute method by high resolution accurate-mass and triple quadrupole mass     spectrometry
  • Tox Explorer collection for drugs of abuse screening and quantitation

Detecting disease

LC-MS is a well-established technique for the quantification of metabolites, lipids, proteins, and various other compounds in clinical research and diagnostics. Mass spectrometry (MS) is often considered the gold standard for the measurement of steroid hormones and is the method of choice for newborn screening. MS-based discoveries of novel clinical biomarkers are also playing increasingly important roles in disease risk assessment, screening, diagnosis, and prognosis, as well as therapy selection and monitoring. Most recently, ambient ionization MS-based techniques have also shown promise for point-of-care (POC) diagnostics. Explore these applications in greater detail through the curated resources below.

Direct mass spectrometry: the future of point-of-care diagnostics

In this presentation, Livia Eberlin, Ph.D., Associate Professor at Baylor College of Medicine, highlights the development of the MasSpec Pen and its applications in surgery, microbiology, and toxicology. This novel POC device is designed to enable medical professionals without MS expertise or experience to take advantage of the rich molecular information it can provide and enables the direct analysis of in vivo and freshly excised tissues.

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Surgeons detect cancerous tissue in seconds with MasSpec Pen

The MasSpec Pen is a hand-held device that acts as an intuitive interface between the surgeon and a mass spectrometer to provide rapid information on tissue identification and cancer diagnostics. Dr. Livia Eberlin explains, “The MasSpec Pen allows surgeons to perform non-destructive molecular analysis and identification of tissues in vivo to identify tissues even before resection, a capability currently unavailable in surgical practice.” Read the full story in this case study.

What we aimed to address with the MasSpec Pen technology was a simple device between the mass spectrometer and the surgeon that was easy to use, biocompatible, and was something that the surgeons could routinely employ in surgery without having training in mass spectrometry.

Dr. Livia Eberlin, Associate Professor, Baylor College of Medicine

Featured technology: Orbitrap Exploris systems

The Orbitrap Exploris 120 provides high resolution and mass accuracy with a compact footprint. This enables easy integration into a clinical setting, such as an operating room, making it the ideal mass spectrometer to pair with the MasSpec Pen.

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Hear from more experts on the latest developments in clinical LC-MS

Untargeted metabolomics in the fight for patient diagnosis

In this presentation, Dr. Annie Evans, Senior Director and Head of Core Research, Metabolon, discusses her research developing metabolomic-based precision medicine approaches to better diagnose and treat rare diseases. Evans and her team are working towards the goal of producing an MS-based single test that could diagnose hundreds to thousands of diseases.

Delivering high-precision healthcare

In this presentation, Dr. Robin Kemperman, a Senior Mass Spectrometrist at the Children’s Hospital of Philadelphia, will discuss how applying a method called high field asymmetric ion mobility (FAIMS) in combination with mass spectrometry (MS) can enhance the quality of projects within global metabolomics initiatives.

Clinical toxicology testing using novel sampling technologies

In this presentation, William Clarke, a Professor of Pathology at Johns Hopkins University School of Medicine, explores innovative sampling technologies such as automated dried blood spot analysis and MasSpec Pen technology for toxicology testing using mass spectrometry.

Additional resources
 • Effortless and Streamlined Workflow for Absolute Quantitation of Therapeutic Monoclonal Antibodies using Promise         Proteomics mAbXmise™ kits and TSQ Altis Plus Mass Spectrometer
 • Simultaneous Detection of Respiratory Infectious Diseases using Immunoprecipitation and Liquid Chromatography-Tandem     Spectrometry
 • High flow LC-MS analysis of plasma digest for protein identification
 • Thermo Scientific™ FAIMS Pro Duo interface Brochure
 • FAIMS Pro interface Smart Note

LC-MS medical devices for IVD use

Faced with the high cost of immunoassay antibodies and reagents, a growing number of clinical diagnostic laboratories are considering LC-MS for laboratory developed tests (LDTs). Despite this, there are few instruments available that are in vitro diagnostic (IVD) compliant and can be used for the development and optimization of LDTs. The new portfolio of Class I medical devices from Thermo Fisher Scientific addresses this need and offers a choice of triple quadrupole MS with the Thermo Scientific TSQ Altis MD Series and the Thermo Scientific TSQ Quantis MD Series for in vitro diagnostic analysis. Powered by a comprehensive software suite that conforms to IVD requirements, with an optional laboratory information system (LIS) connection, these systems are designed to provide clinical labs with options to meet varying sensitivity and productivity requirements. Both MS options are supported by the Thermo Scientific Vanquish MD HPLC system — a compact, yet powerful system with high throughput, speed, and sample capacity.

Explore LC-MS medical devices for IVD use in this brochure and discover 5 reasons why it is time to implement LC-MS for LDTs. Plus, download the resources below to explore the analytical performance of these instruments across a variety of clinically relevant molecules and sample types.

Using LC-MS to distinguish between vitamin D2 and D3

Explore multiple analytical methods for the HPLC-MS/MS analysis of 25-hydroxyvitamin D2 and D3 on a TSQ Altis MD triple quadrupole mass spectrometer.

A reliable and simple method for newborn screening

See how the Vanquish MD HPLC and a TSQ Quantis MD MS were used to quantify 12 amino acids and 13 acylcarnitine in dried blood spots.

Detecting SARS-CoV-2 with mass spectrometry

Learn about the robust, 4-minute, reliable targeted peptide absolute quantification assay developed to detect SARS-CoV-2.

In Vitro Diagnostic Medical Device*

*For in vitro diagnostic use. Specifications subject to change. Availability of product in each country depends on local regulatory marketing authorization status. Not all products are available in all countries. Please consult your local sales representative for details.

Translational research

LC-MS for clinical biomarkers

LC-MS offers a powerful technique for the large-scale screening of clinically relevant biomarkers, as well as for targeted quantification of proteins in complex biological samples. Thermo Fisher Scientific offers clinical translational research solutions that provide comprehensive compound identification and characterization with simple method transfer to select compounds of interest and create a targeted panel for proteomics, metabolomics, and lipidomics analyses. Explore a reproducible and easy-to-implement plasma protein profiling workflow using high-flow UHPLC/MS/MS without depletion.

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LC-MS for therapeutic drug monitoring

Drug monitoring has become a staple in healthcare to improve patient management and enable personalized medicine approaches. LC-MS is increasingly leveraged for therapeutic drug monitoring as it offers a sensitive, specific, and low-cost method for analyzing compounds such as immunosuppressants, antibiotics, antidepressants, chemotherapy, antifungal, and cardiac drugs. Discover a streamlined workflow for absolute quantitation of therapeutic monoclonal antibodies using Promise Proteomics mAbXmise kits and a TSQ Altis Plus mass spectrometer.

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Additional resources
  • Thermo Scientific™ Orbitrap Exploris™ 240 Mass Spectrometer brochure
  • Thermo Scientific™ Vanquish™ Horizon UHPLC System brochure

Front-end solutions

The advent of rapid chromatography techniques and the availability of highly sensitive and selective mass spectrometry platforms have greatly simplified the development of high-throughput bioanalytical methods. Consequently, the primary bottleneck in the analytical process has shifted to sample preparation, which plays a critical role in ensuring the robust performance of the analytical system, particularly in quantitative assays.

A faster path to mass spectrometry analysis

PaperSpray mass spectrometry is a technique where the sample is spotted onto a strip of paper and is extracted and ionized directly at the ion source of the mass spectrometer. Using PaperSpray technology such as the VeriSpray PaperSpray ion source system, researchers can perform direct MS-based analyses with minimal solvent consumption and sample preparation, simplifying their workflows, reducing time to results, and lowering the cost per test. With the VeriSpray ion source, MS results can be obtained in less than two minutes and there is no chromatographic downtime or maintenance. The VeriSpray plate loader and magazine hold up to 10 VeriSpray sample plates, each equipped with 24 paper strips, enabling users to run up to 240 samples unattended. For automated sample spotting, the VeriSpray sample plates are compatible with robotic spotters. Learn more in this brochure and in the specifications sheet for the VeriSpray PaperSpray system.

In this study, see how PaperSpray-MS was used to analyze 21 drugs of abuse in methanol, whole blood, and precipitated blood to determine the utility of protein precipitation.

In this technical note, see how the VeriSpray sample plates and VeriSpray ion source deliver accurate and robust quantitative results for the measurement of EDDP in human whole blood for clinical research.

Enable fast clean up of complex matrices for accelerated online sample preparation with TurboFlow

Turbulent flow liquid chromatography was developed in the late 1990s and combines size exclusion and traditional stationary phase column chemistry to separate macromolecules, such as proteins, from smaller molecules and analytes of interest in biological fluids. Proprietary Thermo Scientific™ TurboFlow™ technology combines diffusion, chemistry, and size exclusion to perform selective online sample cleanup of dirty or difficult matrices prior to HPLC or UHPLC separation and MS analysis. TurboFlow technology reduces sample preparation by up to 95%, lowering costs, labor, and time, reducing ion suppression through greater specificity and cleaner samples, and streamlining method development. TurboFlow technology is utilized by the Thermo Scientific™ Transcend™ TLX UHPLC systems, automatically removing matrix interferences, reducing or eliminating time-consuming preparation procedures for biological samples, and improving sensitivity and reproducibility. Depending on sample complexity, analyte abundance, and MS sensitivity, samples can be directly loaded or precipitated and centrifuged prior to loading.

Achieve up to four times throughput on your single triple quadrupole or high-resolution mass spectrometer

Without requiring any additional bench space, multichannel LC technology such as the Transcend TLX UHPLC System – featuring TurboFlow technology – can enable labs to effortlessly boost sample throughput while maintaining data quality and sensitivity. Transcend TLX systems offer the flexibility to choose from 1, 2, or 4 parallel UHPLC channels to meet any throughput requirements and ensure a high return on investment through maximum mass spectrometer utilization.

In this application note, see how the Transcend II TLX-1 TurboFlow chromatography system coupled to a Thermo Scientific™ Q Exactive™ Focus hybrid quadrupole-Orbitrap™ mass spectrometer provides a simple, fast, highly specific, and sensitive method for the robust determination of cannabinoids in low-volume human wholeblood samples. Plus, discover how researchers at KingMed Diagnostics leveraged multichannel LC and TurboFlow technology, for online sample cleanup of complex matrices, to completely automate the analysis of insulin-like growth factor 1 (IGF-1). KingMed was the first laboratory in China to introduce multi-channel LC combined with HRAM MS for clinical examinations. This was achieved using the Thermo Scientific™ Transcend™ TLX-4 system and Q Exactive Plus hybrid quadrupole-Orbitrap mass spectrometer.

Enhance signal-to-noise ratio ten-fold with FAIMS Pro Duo

The FAIMS Pro Duo is a unique device that interfaces with Thermo Scientific mass spectrometers to enhance the signal-to-noise ratio. When paired with the VeriSpray and TSQ Altis systems, it has demonstrated up to a 10-fold enhancement in the limit of quantitation (LOQ) for detecting doping compounds in urine.

In this presentation, Tony Maus, Ph.D., Assistant Professor at Mayo Clinic, discusses the automated sample analysis of dried blood spots and explores how FAIMS technology can help address the challenges of improving the specificity and reducing interference on molecules of interest.

Orthogonal tools

Beyond LC-MS, Thermo Fisher Scientific also offers a suite of other instrumentation used routinely in the fields of toxicology and clinical research. Explore these technologies in greater detail in the free downloadable resources below.

Staying ahead of regulations for the analysis of steroids in urine with GC-MS/MS

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Breath Biopsy™ with TD-GC-Orbitrap: a non-invasive approach for disease detection

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GC-IRMS: Combat emerging threats in drug abuse with isotope fingerprints

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How do isotope fingerprints support doping control investigations?

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Quantitative analysis of 28 trace elements in human plasma and serum by triple quadrupole ICP-MS for clinical research

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Development of a method for lead screening using DBS

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Success stories

We want to build [diagnostic] tools that will have a real impact on people's lives. We’re on the cusp of making one of those contributions, and it wouldn’t be possible without the support of Thermo Fisher Scientific.

Ian Lewis, PhD, Associate Professor and Director of the Alberta Centre for Advanced Diagnostics

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"We’re working on a method [for lead screening] using dried blood spots in tandem with ICP-MS. What inspires me in my job as a clinical chemist is the ability to provide meaningful answers for physicians and patients.

Jessica Colón-Franco, PhD, DABCC, Section Head of Clinical Biochemistry and Director of the Special Chemistry Laboratory, Cleveland Clinic

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We are developing clinical assays that are relevant in the field of metabolic bone disorders. We have set up ICP-MS methods that are addressing this unmet clinical need, which affects over 1 billion patients in the world.”

Michael Lutz, PhD, Senior Adviser, Osteolabs, GmbH Germany

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Learn more about Thermo Scientific Mass Spectrometry Solutions
for Clinical Research

All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. ANSI is a trademark of the American National Standards Institute (ANSI). ASB is a trademark of the American Academy of Forensic Sciences Corp. Breath Biopsy™ is a trademark of Owlstone Medical Ltd.mAbXmise™ is a trademark of Promise Proteomics. Traceable Opioid Material®, and TOM Kits®, are registered trademarks of the U.S. Department of Health and Human Services. This information is presented as an example of the capabilities of Thermo Fisher Scientific products. It is not intended to encourage use of these products in any manner that might infringe the intellectual property rights of others. Specifications, terms and pricing are subject to change. Not all products are available in all countries. Please consult your local sales representative for details.