Investigation of the metabolite variation in control rat urine using 1H NMR spectroscopy

An exploratory statistical analysis has been undertaken of 640 H-1 NMR spectra of rat urine, obtained from predose and control animals during the course of eight separate toxicology studies. The aim was to determine the degree and type of variation between 1H NMR spectra from such control animals and to investigate the variations in the spectral descriptors based on averaged peak intensities. The results showed that many of the spectral descriptors had skew and/or multimodal distributions, and that it was possible to distinguish between samples of urine collected at different times of day with a success rate of (89%) and to classify 90% of the predose spectra into their correct study group using principal component and linear discriminant analyses. The results show that successful classification can be achieved of NMR spectra of control rat urine, which exhibit more subtle changes than those previously reported when treated and control animals were compared. The results presented here suggest that it will be possible to identify very subtle toxicological changes if care is taken to standardize the experimental conditions used during toxicity screens. (C) 2001 Academic Press.