Abstract
Determination of the purity of a substance traceable to the International System of Units (SI) is important for the production of reference materials affording traceability in quantitative measurements. Post-column isotope dilution using liquid chromatography-chemical oxidation-isotope ratio mass spectrometry (ID-LC-CO-IRMS) has previously been suggested as a means to determine the purity of organic compounds; however, the lack of an uncertainty budget has prevented assessment of the utility this approach until now. In this work, the previously published ID-LC-CO-IRMS methods have not only been improved by direct gravimetric determination of the mass flow of 13C-labelled spike but also a comprehensive uncertainty budget has been established. This enabled direct comparison of the well-characterised ID-LC-CO-IRMS method to quantitative nuclear magnetic resonance spectroscopy (qNMR) for purity determination using valine as the model compound. The ID-LC-CO-IRMS and qNMR methods provided results that were in agreement within the associated measurement uncertainty for the purity of a sample of valine of (97.1 ± 4.7)% and (99.64 ± 0.20)%, respectively (expanded uncertainties, k = 2). The magnitude of the measurement uncertainty for ID-LC-CO-IRMS determination of valine purity precludes the use of this method for determination of purity by direct analysis of the main component in the majority of situations; however, a mass balance approach is expected to result in significantly improved measurement uncertainty.
Highlights
Many methods for assigning purity values such as highperformance liquid chromatography with ultra violet/visible detection (HPLC-UV/Vis) or gas chromatography with flame ionisation detection (GC-FID) that target the impurities of a calibrant often suffer from non-uniformity of response between analytes
Equation (1) can be applied in two different ways: the first involves integrating the signals for m/z = 44 and 45 prior to application of the postcolumn isotope dilution mass spectrometry (IDMS) equation, while the second applies the equation to each data point to produce a mass flow chromatogram which is integrated
A method for determining the purity of valine using postcolumn isotope dilution with a 13C-labelled glucose spike and LC-CO-isotope ratio mass spectrometry (IRMS) instrumentation that does not require an internal/external standard compound of known purity has been developed and a comprehensive uncertainty budget provided. This has allowed a comparison to Quantitative nuclear magnetic resonance spectroscopy (qNMR) for the determination of valine to demonstrate the utility of the ID-LC-COIRMS approach for simple compound
Summary
Many methods for assigning purity values such as highperformance liquid chromatography with ultra violet/visible detection (HPLC-UV/Vis) or gas chromatography with flame ionisation detection (GC-FID) that target the impurities of a calibrant often suffer from non-uniformity of response between analytes. Quantitative nuclear magnetic resonance spectroscopy (qNMR) has emerged as one of the few methodologies capable of providing direct assay purity determinations which are traceable to the International System of Units (SI) [7,8,9] It is, desirable to have a second, independent technique for method validation and to provide confirmatory measurements during reference material characterisation
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