Mass spectrometry (MS) is a powerful analytical technique that provides labs with increased sensitivity and specificity compared to standard immunoassays and other forms of chemical analysis (1,2). However, clinical lab adoption of MS can be deterred by the labor- and time-intensive demands of this complex analytical technique. The limitations of manual MS are often in direct conflict with the tight budgets and staffing constraints that many clinical labs must manage, and they slow down care teams seeking to deliver results as quickly as possible. Automated mass spectrometry systems can help address this challenge by reducing hands-on time, improving turnaround times (TAT), and minimizing the need for tedious manual data review. As automation helps lower barriers to mass spectrometry implementation, the benefits of this analytical technique can be more broadly applied to diverse fields such as therapeutic drug monitoring, clinical toxicology, endocrinology, and more.
Strengthening mass spectrometry workflows
Mass spectrometry accurately measures a wide range of biomolecules by examining their mass-to-charge ratio and reporting the results as a series of “peaks” as the information is captured by ion detectors. The specificity and sensitivity of MS is often enhanced by applying liquid chromatography to MS detection. Liquid chromatography separates molecules based on their physicochemical properties and introduces them into the mass spectrometer. The analytical power of mass spectrometry can be further increased through an approach known as tandem mass spectrometry, where molecules are fragmented into characteristic products. Because of the complementary strengths of these techniques, these analytical assays are frequently combined into a process known as LC-MS/MS (liquid chromatography-tandem mass spectrometry) — the most commonly employed MS approach in the field of clinical chemistry (3).
Yet adoption of LC-MS/MS has historically required significant investment. LC-MS/MS workflows are tailored to each analyte category, requiring labs to develop and validate their own laboratory developed tests (LDTs). The process of building LDTs can be fragmented, with MS reagents sourced from multiple suppliers and multi-step workflows that include sample preparation, optimization of chromatography columns and mobile phases, and complex calibration procedures. Furthermore, mass spectrometry protocols frequently differ between sites, creating challenges in comparing results and expanding LC-MS/MS offerings.
Fortunately, in vitro diagnostic device companies have now developed reagents and systems that can reduce the need to design assays in-house. For example, new paramagnetic microparticles can eliminate manual sample prep by selectively capturing analytes from complex biological matrices. Pre-optimized high-performance liquid chromatography (HPLC) cartridges are now commercially available, eliminating the need for in-house development of chromatography separations. Purchasing reagents from a commercial supplier provides enormous benefits for standardizing workflows across locations. Together, these components help create a more defined and consistent LC-MS/MS adoption pathway for clinical labs, reducing the technical complexity of mass spectrometry implementation while also introducing harmonization of measurements.
Advancing LC-MS/MS with automation
Improved commercial access to standardized reagents has also led to the development of automated LC-MS/MS analyzers. Automation is a critical step forward for the industry, as manually intensive MS analysis burdens clinical lab staff and slows operational turnaround times (TAT). In one multi-lab study that examined 93 LC-MS/MS workflows across six different analyte categories, the median turnaround time from batch start to completion of data review was 26 hours (4). For more complex samples, such as testosterone and vitamin D, timelines were reported to reach upwards of 72 hours (4). These slow workflows also include significant labor demands. Manual LC-MS/MS can require over 4 hours of hands-on time, and data review can be tedious, with each peak requiring individual review by specialized staff (4,5). Yet the use of LC-MS/MS in clinical settings continues to rise, despite these time and labor demands, which speaks to the enormous diagnostic value and patient-care benefits that this analytical technique can provide (1-3).
Automated analyzers help make LC-MS/MS more accessible. The same study performed across seven labs found that automated workflows reduced median TAT to 1.5 hours with a median hands-on time of only 5 minutes (4). This rapid automation is possible in part due to the availability of simplified reagent systems that offer ready-to-use packs and containers, eliminating the need for in-house preparation of internal standards or mobile phases (5). Sophisticated algorithms also speed up data reduction, automatically interpreting results based on pre-defined parameters, while flagging abnormal peaks for human review. Together, these innovations aim to make LC-MS/MS a routine and scalable analytical technique that can enhance diagnostic capacity in clinical labs worldwide.
The continually expanding applications of LC-MS/MS
Patients have already benefited from the introduction of LC-MS/MS into clinical labs. New steroid assays for mass spectrometry allow labs to routinely run high-quality LC-MS/MS analyses for endocrinology applications (6). Metabolite analysis can now be augmented with LC-MS/MS as labs harness the sensitivity of mass spectrometry to examine vitamin levels in patient samples (6). As more labs access what was previously a burdensome and inefficient analytical tool, new applications and technologies are likely to be developed, which may benefit newborn screening, disease monitoring, therapeutic drug monitoring, and more.
Innovations in sample preparation and automation have come together to address crucial shortcomings of mass spectrometry. Care teams can now access this powerful technique with relative ease, and mass spectrometry can accommodate the budgets and staffing realities of clinical labs. By condensing protocols that took days into a couple of hours, automated LC-MS/MS technology is a significant step forward for clinical lab staff hoping to provide the highest level of care to their patients.
References
- French D. Clinical utility of laboratory developed mass spectrometry assays for steroid hormone testing. J Mass Spectrom Adv Clin Lab 2023; doi:10.1016/j.jmsacl.2023.01.006
- Vogeser M. Mass spectrometry in the clinical laboratory — Challenges for quality assurance. Spectroscopy Online. https://www.spectroscopyonline.com/view/mass-spectrometry-clinical-laboratory-challenges-quality-assurance (Published July 2015. Accessed April 2026).
- Schreiber A and von Czapiewski K. Recent trends in the use of LC-MS-MS for the testing of food and environmental contaminants. Spectroscopy Online. https://www.spectroscopyonline.com/view/recent-trends-use-lc-ms-ms-testing-food-and-environmental-contaminants (Published March 2009. Accessed April 2026).
- Vermeersch P, de Jonge R, Miyazawa T, et al. Comparison of six serum analyte workflows using routine liquid chromatography-tandem mass spectrometry methods at multiple laboratories with the Cobas i 601 analyzer, an automated mass spectrometry system. Clin Chem Lab Med 2026; doi:10.1515/cclm-2025
- Roche Diagnostics. Fueling a new era of innovation in mass spectrometry. https://diagnostics.roche.com/content/dam/acadia/whitepaper/400/200/MC-US-17779-External-cobas%20Mass%20Spec%20solution%20white%20paper.pdf (Published October 2025. Accessed July 2026.)
Roche Diagnostics. Roche expands mass spectrometry menu to include steroid assays receiving CLIA “moderate complexity” designation. https://diagnostics.roche.com/us/en/news-listing/2026/ionify-clia-steroid-assays-mass-spectrometry.html (Published March 2026. Accessed July 2026.)
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