Development of a Standard Reference Material for Metabolites in Plasma 

Metabolomics is a relatively new field that builds upon work in genomics and proteomics. Metabolomics can provide a unique perspective on the biochemical status of an organism through broad surveys of the metabolites in relevant samples such as plasma. These measurements may provide insight into the chemical and molecular pathways that are involved in normal function as well as disease. The National Institutes of Health (NIH) Metabolomics Technology Development Initiative reflects the need for new tools to identify and quantify metabolites in human systems. NIST is working with NIH to develop a plasma-based SRM that can be utilized to evaluate new procedures for measuring metabolites and to improve the reproducibility of measurements by providing a stable standard for comparison.

Because metabolite levels can provide insight into the response of an organism to disease, metabolomics research may lead to new approaches to disease diagnosis and treatment. Metabolite profiling also shows promise for examining the efficacy and potential toxicity of drugs during the development process. Metabolomics experiments can be either identification (also called discovery) based or quantification based; usually a combination of both approaches are used. Mass spectrometry (MS) and NMR remain the primary techniques utilized in metabolomics, and MS-based methods are typically coupled with a chromatographic separation. No single technique can provide a full catalog of all the metabolites in a sample, and sample handling and preparation techniques can affect both metabolite identification and quantification. For these reasons, comparison of data sets from different metabolomics experiments can be quite difficult. NIST has developed a Standard Reference Material (SRM) for metabolomics, with the goal of providing a stable, well-characterized reference material for metabolomics research.

SRM 1950 Metabolites in Human Plasma consists of a plasma pool collected from an equal number of men and women and with a racial distribution that reflects the U.S. population. The initial value assignment phase for this SRM has focused on metabolites for which NIST has existing methods. The concentrations of more than 30 metabolites, including electrolytes, hormones, glucose, creatinine, vitamins, and fatty acids have now been determined by LC-MS, LC-MS/MS, and GC-MS methods. Quantification was based upon isotope-dilution methodology when possible. In addition to the quantitative aspects of this SRM, additional qualitative information may be valuable for those interested in metabolite profiling and identification rather than absolute quantification. Therefore we will be pursuing identification of additional metabolites through a variety of techniques, including LC-MS, GC-MS, NMR, and GCxGC-TOF-MS analysis.  

Major Accomplishments:

• The SRM has been designed and produced in collaboration with NIH.
• Measurements have been completed for more than 30 analytes in SRM 1950. Many of these measurements were performed using isotope-dilution methodology.