Clinical Mass Spectrometry
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Importance of Stable Isotope Standards and Their Implementation in Clinical Mass Spectrometry
Andrew J. Percy, PhD
Cambridge Isotope Laboratories, Inc.
Richard Tyburski
ASI Chemicals LLC
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.
MS is a fundamental and versatile technique for such analyte measurements due to its sensitivity, specificity, throughput, and multiplexicity. Stable isotope-labeled (SIL) standards are integral to this analysis, as noted by the references below. Another example is the Researcher Perspective from Drs. Braunstein and Tim West (C2N Diagnostics), which provides an overview of the stable isotope labeling kinetic (SILK™) assay developed to measure blood-derived protein biomarkers, such as Aβ isoforms, involved in 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.
Resources
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?
What is the tolerance for CIL’s 0.1 mg packaged sizes?
The tolerance is ±10% for these particular items.
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. 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 metabolomics. Metabolomics, 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

Krista Backiel
Marketing Manager and Clinical MS Manager
Krista Backiel is responsible for managing and promoting products that are utilized in metabolomics and clinical/diagnostic MS. She spends a lot of her time developing new products to assist customers in their diverse research efforts.
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Andrew Percy, PhD
Senior Applications Chemist – Mass Spectrometry
Dr. Andrew Percy is the Senior Applications Chemist for Mass Spectrometry and the MS ‘Omics Product Manager at CIL. His responsibilities minimally involve providing technical support, overseeing product development, identifying new product market opportunities, assisting in the analysis of product-related applications, and writing/reviewing marketing literature.
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