Isotope dilution mass spectrometry: definitive methods and reference materials in clinical chemistry.

The application of gas chromatography-mass spectrometry (GC-MS) for the quantitative analysis of endogenous compounds as well as drugs in clinical biochemistry is taken into account. For this purpose, it is of the utmost importance the choice of a good internal standard (IS). It is demonstrated that the best IS in GC-MS is a stable isotope-labelled analogue of the analyte. In this case only we can speak of isotope dilution mass spectrometry. All the advantages and disadvantages inherent to the use of such a molecule as IS are discussed. The use of a calibration curve to perform the quantitative analysis is described, together with the criteria applied for the definition of the reliability of a method (precision, accuracy and limit of quantification). Examples taken from the literature are described.