Proton NMR spectroscopy as a means to quantify lipoprotein subclasses has received wide clinical interest. The experimental part is a fast routine procedure that contrasts favourably to other lipoprotein measurement protocols. The difficulties in using 1H NMR, however, are in uncovering the subclass specific information from the overlapping data. The NMR-based quantification has been evaluated only in relation to biochemical measures, thereby leaving the inherent capability of NMR rather vague due to biological variation and diversity among the biochemical experiments. Here we will assess the use of 1H NMR spectroscopy of plasma per se. This necessitates data for which the inherent parameters, namely the shapes and areas of the 1H NMR signals of the subclasses are available. This was achieved through isolation and 1H NMR experiments of 11 subclasses—VLDL1, VLDL2, IDL, LDL1, LDL2, LDL3, HDL2b, HDL2a, HDL3a, HDL3b and HDL3c—and the subsequent modelling of the spectra. The subclass models were used to simulate biochemically representative sets of spectra with known subclass concentrations. The spectral analyses revealed 10-fold differences in the quantification accuracy of different subclasses by 1H NMR. This finding has critical significance since the usage of 1H NMR methodology in the clinical arena is rapidly increasing.

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