THE EVOLUTION AND FUTURE OF ISOTOPE DILUTION MASS SPECTROMETRY FOR THE PROVISION OF BIOCHEMICAL REFERENCE VALUES

Over the last two decades the use of isotope dilution calibration, coupled with mass spectrometric detection, has become the method of choice by National Measurement Institutes (NMIs) participating in Key Comparisons (KC) organised by the working groups of the Consultative Committee for Amount of Substance: Metrology in Chemistry (CCQM). This favoured approach derived from the group’s necessity to have measurement results that were directly traceable to the international system of units (SI). The description of IDMS as a primary ratio method of analysis further established the approach at the heart of all reference measurement procedures and in establishing the “true” amount of a measurand in the sample provided.

This presentation aims to plot the evolution of the IDMS measurement procedures, from first-hand experience, for providing reference values for the characterisation of certified reference materials and for participation in KC. Examples of the use of IDMS in the characterisation of simple to more complex solutions and solid matrix materials will be used to highlight potential gaps in the IDMS traceability chain and question the claim of it being a primary ratio method. The evidence provided will suggest that the NMIs established the chemical knowledge and analytical approaches required to bridge these gaps and in doing so, ensured the equivalence of results obtained at the NMI level.

The evidence of how this established equivalence between NMIs is disseminated to routine testing laboratories is emerging. However, issues have arisen when comparing IDMS values with consensus values in proficiency testing schemes which suggest the results may not be compatible. A greater understanding of these differences may be essential in establishing “fit for purpose” metrological traceability.

Some NMIs have extended the IDMS approaches for the characterisation of protein materials, with the potential of offering the same level of equivalence between NMIs as those experienced with smaller molecules. In these emerging areas, the requirement for NMIs to engage at the research stage is essential in establishing a description of the measurand that will both satisfy the end user of the measurement whilst enabling metrological traceability of the results. But amount is but one descriptor, in biological systems the location, structure, interaction and mechanics are often also critical descriptors. The future will require the use of many different measurements from many different technologies, just to adequately describe the measurand. The success of this interaction is key to the success of the metrological impact in biochemical sciences.