Application of the combination of isotope ratio monitoring with isotope dilution mass spectrometry to the determination of glucose in serum

Isotope ratio monitoring combined with n(C-13)/n(C-12) isotope dilution mas s spectrometry (IRM/IDMS) provides results of low uncertainty of the order of 0.1% if it is applied to the analysis of simple mixtures as found in org anic chemistry, even if only low C-13 spike additives to the sample are use d. If the method is applied to the analysis of systems that require large-s cale sample preparation prior to the measurement, such as the determination of glucose in serum, the results obtained exhibit a higher uncertainty tha t is comparable to that of the conventional gas chromatography/isotope dilu tion mass spectrometry (GC/IDMS) method. The reason for this observation is that the small contribution that the IRM/IDMS method makes to the uncertai nty budget of the result is superimposed on a large contribution due to the sample preparation. It appears therefore that the IRM/IDMS method has no a dvantage over the conventional GC/IDMS method. However, if a series of meas urements is carried out, and if a suitable experimental design is chosen, t he IRM/IDMS method can provide valuable additional information. The influen ce of sample preparation on each individual result can be quantified as its deviation from the average value of all results of the series. From these data conclusions can be drawn for an improvement in sample preparation. Cop yright (C) 2001 John Wiley & Sons, Ltd.