Clinical Mass Spectrometry

Clinical laboratory medicine has evolved and diversified over the past few decades. Although the field has seen major advancements (in terms of methodology, instrumentation, informatics, and automation) and transitions (away from conventional immunoassays), mass spectrometry (MS) is now utilized across several areas of diagnostics. This encompasses therapeutic drug monitoring, toxicology, and endocrinology testing, among other areas of screening. 

Mass spectrometry (MS) is a fundamental and versatile technique for such analyte measurements due to its sensitivity, specificity, throughput, and multiplexicity. Stable isotope-labeled standards are integral to this analysis, as noted by the references below. Another example of clinical mass spectrometry is the work described in the Researcher Perspective from Joel Braunstein, MD, and Tim West, PhD (C2N Diagnostics). They provide an overview of the stable isotope labeling kinetic (SILK™) assay developed to measure blood-derived protein biomarkers, such as α-β isoforms, involved in the study of Alzheimer‘s disease and to track its progression.

Cambridge Isotope Laboratories, Inc. is proud to offer a variety of analytical standards for identification/quantification in clinical MS samples. These standards are highly characterized for analytical purposes, suitable for use in a variety of sample types, and available in various packaging sizes and formats.

Stable Isotope-Labeled Products for Metabolic Research

❛❛Quantitative analysis in clinical diagnostics using mass spectrometry remains a difficult endeavor particularly for small molecules due to chemical similarity and isobaric forms of many substances. Both chromatography and the use of isotopically labeled internal standards to perform small-molecule quantification are required to obtain good quantitative results in many applications. The use of isotopically labeled internal standards remains the best solution as these standards ideally match the chemical behavior of their analytes, thus leading to better quantification than obtained when using structure homologues with physicochemical characteristics.❜❜

– David C. Kasper, PhD | CEO, ARCHIMED Life Science

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Frequently Asked Questions

What are the key criteria for selecting stable isotope-labeled standards for clinical measurements? These exogenous compounds must be structurally unique (within a given sample type) and similar (to the native target, from a physicochemical standpoint) as well as resolvable by MS (≥3 Da generally preferred), free from H/D exchange (if D standards are employed), and ideally co-elute (with their native target).

How and when should the internal standard(s) be added in the workflow? The IS should ideally be added in the first step after mixing/pipetting the sample. This should be identical biochemically to the target analyte and be added precisely to the samples (as well as calibrators and QCs) to ensure recovery/sample variance correction.

What is a useful reference for conducting metabolomic assays in the clinic as well as measuring and reporting this data? The recently published “Bioanalytical Method Validation: Guidance for Industry” document (US FDA, May 2018) outlines the latest recommendations and acceptance criteria for method development, validation, and application as well as documentation and reporting. The bioanalytical methods these pertain to are human clinical studies, which can be used to quantitatively determine the levels of metabolites in biosamples for biomarker analysis, for example.

What is the tolerance for CIL’s 0.1 mg packaged sizes? The tolerance is ±10% for these particular items.

Example References

Yin, Y.; Yu, S.; Qiu, L.; et al. 2019. Establishment of a rapid and simple liquid chromatography tandem mass spectrometry method for measuring aldosterone in urine. J Chromatogr B Analyt Technol Biomed Life Sci, 1113, 84-90. PMID: 30901733
Comhair, S.A.A.; Bochenek, G.; Baicker-McKee, S.; et al. 2018. The utility of biomarkers in diagnosis of aspirin exacerbated respiratory disease. Respir Res, 19(1), 210-216. PMID: 30376852
Mertens, B.; Orti, V.; Vialaret, J.; et al. 2018. Assessing a multiplex-targeted proteomics approach for the clinical diagnosis of periodontitis using saliva samples. Bioanalysis, 10(1), 35-45. PMID: 29243487
Lindahl, A.; Heuchel, R.; Forshed, J.; et al. 2017. Discrimination of pancreatic cancer and pancreatitis by LC-MS metabolomicsMetabolomics, 13(5), 61. PMID 28413374   
Xu, W.; Li, H.; Guan, Q.; et al. 2017. A rapid and simple liquid chromatography-tandem mass spectrometry method for the measurement of testosterone, androstenedione, and dehydroepiandrosterone in human serum. J Clin Lab Anal, 31(5). PMID: 27911021   
Gervasoni, J.; Schiattarella, A.; Primiano, A.; et al. 2016. Simultaneous quantification of 17-hydroxyprogesterone, androstenedione, testosterone and cortisol in human serum by LC-MS/MS using TurboFlow online sample extraction. Clin Biochem, 49(13-14), 998-1003. PMID: 27208555   
Yang, Y.; Rogers, K.; Wardle, R.; et al. 2016. High-throughput measurement of 25-hydroxyvitamin D by LC-MS/MS with separation of the C3-epimer interference for pediatric populations. Clin Chim Acta, 15(454), 102-106. PMID: 26772722   
Peitzsch, M.; Dekkers, T.; Haase, M.; et al. 2015. An LC-MS/MS method for steroid profiling during adrenal venous sampling for investigation of primary aldosteronism. J Steroid Biochem Mol Biol, 145, 75-84. PMID: 25312486