Project Details Methods for the SI Value Assignment of the Purity of Organic Compounds for use as Primary Reference Materials and Calibrators

Project No.:
2013-025-2-500
Start Date:
01 December 2013
End Date:

Objective

To prepare an international best practice guidance document for the SI-traceable value assignment of the purity (mass fraction content of the main component) of organic compounds intended to be used as primary standards and calibrators for establishing traceable measurement results in analytical chemistry.

Description

Analytical Chemistry Laboratories are required to demonstrate the metrological traceability of their measurement results in order to operate in conformity with the requirements of ISO 17025. In the case of organic analysis, the metrological traceability to the SI of the result of an analysis for an organic compound is generally achieved through linkage to a pure primary calibrator material of the defined compound, the mass fraction purity of which has been established in a manner that is also traceable within a stated uncertainty to the SI. The primary calibrator material may be a Certified Reference Material (CRM) or when not available a laboratory may choose to value assign a pure material with valid methods.

Agreement on what constitute valid methods and best practice to measure the content of the main component of a calibrator material within a stated measurement uncertainty is needed and not currently available. The purpose of this report is to describe the approach, performance and applicability of the main methods used to determine purity:

  1. Mass balance
  2. Thermal analysis
  3. Assay techniques
  4. Quantitative NMR

In addition a statistical section will recommend how to combine data, deal with value assignment as the upper limit values corresponding to 100% purity are reached, including the use of asymmetric uncertainties, and how to report and propagate the standard uncertainty associated with the assigned values.

The resulting document will provide an international reference document and guidance for analytical laboratories, CRM manufacturers and accreditors on valid methods for the assignment of purity of organic calibrator materials, thus providing the basis for metrological traceability of measurement results and their global metrological comparability.

Progress

July 2014 – Project announcement published in Chem. Int. July-Aug 2014, p. 15; DOI: 10.1515/ci.2014.36.4.15a

August 2020 update – The manuscript for a Technical Report has been completed that describes the approach, performance and applicability of the principal methods used to determine organic purity – mass balance, quantitative NMR, thermal methods and other direct assay techniques. A statistical section reviews best practice for combination of data, value assignment as the upper limit values corresponding to 100% purity are reached and how to report and propagate the standard uncertainty associated with the assigned values.

 

August 2021 update – A review of this project was presented by the TGC during the 2021 IUPAC Congress, in the Society session titled “IUPAC Role in Global Affairs” and recorded with the following abstract:

Fifty years have elapsed since the publication in 1971 of the IUPAC Monograph “Characterization of Chemical Purity of Organic Compounds”, which described the methodologies established by the 1960s for higher-order purity assignment of organic compounds. In the intervening decades technical capabilities have been enhanced considerably and their applicability broadened substantially through two separate but complimentary developments: firstly, methods based on high-performance liquid chromatography coupled to sensitive detection systems that provide both selective and sensitive methods for analyte detection and quantification and secondly the widespread application of quantitative nuclear magnetic resonance (qNMR) spectroscopy to directly assign the content of the primary component in an organic material.

These occurred concurrently with an increasing focus on the metrological infrastructure required to support growing regulatory requirements for third-party accreditation to ISO standard 17025 of testing laboratories and the analytical methods used for routine analysis. Establishing reliable, comparable calibration hierarchies for the quantification of an organic analyte in a given matrix at any concentration is anchored on the availability of traceable primary calibrators for each quantified analyte.

In 2013 the IUPAC Analytical Division approved a project to deliver a Technical Report on “Methods for the SI-Traceable Value Assignment of the Purity of Organic Compounds”. This talk will summarize the background to the project and the challenges encountered in the development of the Report, currently in the final stages of review for publication in Pure and Applied Chemistry. This report provides an overview of the approach, performance and applicability of the principal methods in contemporary use to determine organic purity including mass balance, quantitative NMR, thermal methods and direct-assay techniques where it is desired that the assigned values for the mass fraction or mole fraction content of the primary organic component  in the material  be traceable to the SI units for mass and/or amount of substance. A statistical section of the report reviews best practice for the combination of data, value assignment as the upper limit values are approached and how to report and propagate the standard uncertainty associated with the assigned values.

 

Last update 8 Sep 2021