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% TOTAL ION INTENSITY m/z 100

Figure 42. Scatter plot of the ion intensities at m/z 100 versus m/z 150 for the analysis of single drops of unprepared urine from 39 normal controls (•) and three-patients (o). In the alkaptonuria case m/z 150 corresponds to the molecular ion of the (M-H2O) pyrolysis fragment of homogentisic acid (MW 168). Similarly, in the case of the unknown aciduria m/z 100 later proved to correspond to the molecular ion of the (M-H2O-CO2) pyrolysis fragment of- hydroxymethylglutaric acid (MW 162). The m/z 100 ion in the urine of the patient on penicillin medication is a characteristic penicillin fragment (together with other ions, e.g. at m/z 115) of unknown structure. The normal controls were not on special diets.

As shown already in the microbiological applications, Py-MS techniques are useful for the differentiation and identification of cells. In fact, some preliminary applications of differentiation of diseased versus normal cells, viz. fibroblasts from patients with inborn errors of metabolism (ref. 159) or leukaemic white blood cells (refs. 110, 158, 164), have been described. Despite promising results, it should be realized that the analysis of highly complex mammalian cells poses almost insurmountable problems with regard to the selection of representative samples owing to the high level of inter- and intra-individual variability encountered. These problems are even more pronounced when applying Py-MS techniques to whole tissues, e.g. the differentiation of diseased muscle tissue such as discussed in Chapter 6. However, by selecting carefully defined tissue samples the problems of inter- and intra-individual variability can be brought back to manageable proportions, as was demonstrated by Van Haard et al. in the analysis of cataractous eye-lens nucleus tissues (ref. 96). A model system using frog embryo cell clones was recently

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