As of June 12, 2018 our Privacy Policy has been updated. For individuals in the European Union, CIL uses cookies on this website. Please review the new privacy statement to see how. By continuing to use this website you agree to us using cookies in accordance with our privacy statement. Click here for the new privacy statement..OK

Metabolic Research

Clinical/Diagnostic MS

Stable Isotopes in Drug Development and Personalized Medicine

Marc Hellerstein, MD, PhD
Professor of Human Nutrition (Calloway Chair)
University of California at Berkeley

A researcher perspective on the use of stable isotopes in the emerging era of personalized medicine.


  • Stable Isotopes in Drug Development and Personalized Medicine
  • Stable Isotope Labeling Kinetics (SILK™) to Measure the Metabolism of Brain-Derived Proteins Implicated in Neurodegeneration

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 samples and diagnostic MS measurements. These standards (listed in the “Stable Isotope-Labeled Products for Mass Spectrometry” catalog) are highly characterized for analytical purposes, suitable for use in a variety of sample types, and available in various packaging sizes and formats.
 

Resources

Stable Isotope Standards for Mass Spectrometry Catalog
Research Use Statement
Product Quality Designation Chart
 
 
Human IGF-1 (Lys-13C6,15N2 , 99%; Arg-13C6, 15N4, 99%) Datasheet
   

 

Frequently Asked Questions 

What are the key criteria for selecting stable isotope-labeled standards for clinical or diagnostic 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.
 

 

References

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

Krista Backiel

Krista Backiel

Marketing Manager and Metabolomics 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.

More
Andrew Percy, PhD

Andrew Percy, PhD

Senior Applications Chemist – Mass Spectrometry

Dr. Andrew Percy is the Senior Applications Chemist for Mass Spectrometry. His responsibilities minimally involve overseeing product development, identifying new product market opportunities, assisting in the analysis of products for MS ‘omics applications, and providing technical support to customers.

More