Exploring the value of liquid chromatography
tandem mass spectrometry in the clinical lab

Over the past decade, tandem mass spectrometry combined with liquid chromatography (LC-MS/MS) has been increasingly applied across a multitude of important diagnostics niches. Covering a wide range of analytes in clinical toxicology, endocrinology, inborn errors of metabolism, and therapeutic drug monitoring, LC-MS/MS now forms part of routine testing for many clinical laboratories. It is often irreplaceable in many circumstances, benefiting from higher sensitivity and selectivity than other techniques such as automated immunoassays. However, the application of LC-MS/MS is still burdensome in many settings, with in-house lab developed test (LDT) designs relying on highly specialized staff.

In this comprehensive SelectScience resource, built in partnership with Waters™, we take a closer look at how LC-MS/MS instrumentation has advanced to support this increased uptake, shaping the market with IVD labeled instruments and reagent sets. Through the various resources and case studies included, we also explore examples of how clinical scientists have been successfully developing and implementing LC-MS/MS, exploring its value as an alternative technique in their laboratory, and how it has improved both their testing menus and results for better patient care.

Clinical toxicology

Offering improvements in specificity, flexibility, and sample throughput when compared with other techniques such as gas chromatography-mass spectrometry (GC-MS) and immunoassays, LC-MS/MS has seen enormous growth in routine toxicology laboratories.

For example, in drugs of abuse testing, GC-MS has long been the gold standard over immunoassays as it also enables the identification of unknown abused drugs from a urine sample. However, to achieve the desired analytical sensitivity and resolution, most compounds of interest need to undergo derivatization to make them more volatile and compatible with GC analysis. In contrast, LC-MS/MS is ideal for non-volatile molecules, meaning an efficient separation can be achieved with less sample preparation.

From the analysis of pain management drugs, to blood alcohol testing, and depressants, explore more applications of LC-MS/MS in the toxicology laboratory below:

Test tube


With endocrinology investigations, immunoassays are a popular choice because they are easy to implement and provide rapid results, but there are cases when these automated solutions are either not available or suitable, and issues with interference and cross reactivity are well documented. The specificity of mass spectrometry has also revealed that many automated immunoassays do not measure steroid hormones accurately, particularly in the settings of deranged physiology.

In these situations, more and more laboratories are turning to chromatographic and spectrometry-based techniques like LC-MS/MS to provide reliable and accurate diagnostics for their patients.  

Explore case studies and examples of the analytical performance of LC-MS/MS for hormones analysis:

Dr. Joe El-Khoury

Director of the clinical chemistry laboratory at Yale New Haven Health, Dr. Joe El-Khoury, shares how his team are developing new mass spectrometry-based methods for endocrinology investigations.

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Metabolic disorders

The analysis of metabolites in human body fluids has posed a significant challenge to clinical scientists because of their chemical diversity and dynamic concentration range. However, technological advances in LC-MS/MS have proven revolutionary for metabolomics analysis, allowing metabolomes to be explored more deeply and enabling the discovery of key new disease metabolite biomarkers.

Advances in LC-MS/MS method development have also led to improvements in diagnostic sensitivity and specificity when analyzing disease markers such as lipids, carbohydrates, amino acids and biogenic amines, vitamins, and organic acids. With screening for inborn errors of metabolism (IEMs) for example, the introduction of tandem mass spectrometry (MS/MS) has allowed the simultaneous detection of multiple analytes, improving outcomes of patients with IEMs through early disease identification and treatment.

In the resources below, Waters shares how its flow injection analysis tandem mass spectrometry (FIA-MS/MS) platform, the RenataDX™ System, can be leveraged to quantify amino acids, free carnitines and acylcarnitines in dried blood spots:

RenataDX™ System from Waters
RenataDX System from Waters
RenataDX System

RenataDX System – Tips and tricks for flow-injection tandem mass spectrometry (FIA-MS/MS)

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RenataDX System

RenataDX System: Analytical performance for amino acids, free carnitines and acylcarnitines in dried blood spots

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RenataDX System

RenataDX System: Analytical performance for butyl esters of amino acids, free carnitine, and acylcarnitines in dried blood spots

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Therapeutic drug monitoring

Monitoring of therapeutic drugs, such as antiepileptics, immunosuppressants, and alkylating agents, has benefited immensely from the increased analytical sensitivity and selectivity that LC-MS/MS provides over other methods. In some cases, it may also be the only viable method of quantification of drugs without natural chromophores or fluorophores.  

LC-MS/MS, however, is a more involved technique than alternatives such as automated immunoassays, and, as in the other diagnostics areas mentioned above, there is a requirement for labs to follow local regulatory guidelines and international standards when developing and validating the technology as a laboratory developed test.

Fortunately, instrument manufacturers like Waters have responded by producing dedicated calibrator and quality control sets, designed to provide clinical laboratories with metrological traceability and accurate results.

ACQUITY UPLC I-Class/Xevo TQD IVD System by Waters
ACQUITY UPLC I-Class/Xevo TQD IVD System by Waters
From immunosuppressive agents to chemotherapy drugs, explore example applications of LC-MS/MS in therapeutic drug monitoring below:  

Metrological traceability of the Waters™ MassTrak™ Immunosuppressant Calibrator and Quality Control Sets

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ACQUITY UPLC I-Class SM-FL/Xevo TQ-S micro IVD System: Analytical performance for immunosuppressive agents

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ACQUITY UPLC I-Class/Xevo TQD IVD System: Analytical performance for antiepileptic drugs

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ACQUITY UPLC I-Class/Xevo TQD IVD System: Analytical performance for an alkylating agent

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End-to-end analytical solutions

Despite the widely recognized benefits of LC-MS/MS technology, as a relatively new technology that is less automated than immunoassays, there are still hurdles to overcome in its implementation. Factors such as the expertise required to develop a new LC-MS/MS method and LDT validation can hold clinical laboratories back. Fortunately, manufacturers are working to reduce these pain points.

As a leading clinical LC-MS/MS solutions partner, Waters provides medical devices that are designed to optimize your laboratory’s workflow and span end-to-end, from pre-analytics (site preparation and prep solutions), to analytics (LC to LC-MS/MS), and post-analytics (informatics).

Combining quality products with ease-of-use, flexibility and improved user experience, Waters solutions allow you to customize your instrumentation to your analytical needs providing accurate results, while maintaining regulatory compliance.


How to expand your clinical capabilities infographic

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Quick guide to LC-MS/MS workflows in clinical diagnostics - eBook

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Clinical solutions brochure

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Explore the MassTrak IVDLC-MS/MS portfolio from Waters below:

Mass Trak portfolio
MassTrak ACQUITY UPLC I-Class PLUS/Xevo TQ-S micro IVD System
MassTrak ACQUITY UPLC I-Class PLUS/Xevo TQ-XS IVD System
MassTrak ACQUITY UPLC I-Class PLUS/Xevo TQD IVD System
MassTrak Endocrine Steroid Calibrator and Quality Control Sets
MassTrak Immunosuppressant Calibrator, Quality Control, and Internal Standard Sets
FlexCHOICE Instrument Service Coverage: Solutions for the Clinical Diagnostics Laboratory

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