a b c d 1 1., E \ t e t ; t3 2 0 5 10 15 0 5 10 15 0 5 0 5 Time (rrin) Figure 2 HPLC chromatograms obtained during the analysis of (a) control plasma and (b) 15 min plasma sample with mobile phase 1 and (c) control plasma and (d) 6 h plasma sample with mobile phase 2. Peak identities: 1. dansylated endogenous material 2. dansyl-DPT 3. dansyl-taurineamide. containing dansyl chloride (1.5 mg) in a tapered centrifuge tube, which was gently shaken for 30 min. Chloroform (4 ml) was added and the procedure for the treatment of plasma samples was followed. Calibration curves were prepared by adding aqueous solutions (100 ul) containing known amounts of taurineamide to distilled water (500 IlI) and control urine (50 ,ul). Because of the difference in polarity between the DPT and taurineamide dansyl derivatives, it was not possible to assay both compounds with a single mobile phase. Examples of chromatograms obtained by this assay for the measurement of DPT and taurineamide concentrations in plasma from a patient who had received 4 g of taurolin by intraperitoneal instillation are shown in Figure 2. The overall derivatisation/extraction yield for taurineamide from plasma was 74% and was independent of the taurineamide concentration up to 100 ,ug ml-'. The overall yield for DPT varied from 19% at 5 ,ug ml-' DPT to 26% at 40 Mg ml-' DPT. Increasing the amount of dansyl chloride, reaction time or the temperature, did not improve the recovery of DPT or taurineamide. The precision (rela-tive standard deviation) of the method estimated from seven replicate analyses was 4.7% for DPT (14.9 ,ug ml-') and 3.7% for tuarineamide (50.6 ug ml-') in blank plasma. Although the overall recovery of DPT is low the precision of the method indicates it is reproducible. Improved sensitivity might result if a fluorescent detector was used in place of a UV detector.
First published in 1989, this book acknowledges that new drugs, food additives and other compounds need to be carefully screened for toxic side-effects. The bulk of this study is devoted to the practical questions of 'what toxicological studies should we perform?' and 'how should we perform them?' Compounds which undergo toxicity testing may be conveniently categorised as those which are intended for administration to man and those which are not. The former include pharmaceuticals to be used medicinally or prophylactically and chemicals which are added to our food, drinks or medicine to improve their stability, appearance or palatability. Since it is on pharmaceuticals that the most comprehensive toxicological evaluations are generally performed, this book has been directed primarily towards to toxicological evaluation of potential new drugs. The principles and methodology of toxicological evaluation of other types of compounds are essentially similar.
Taurolin, a broad spectrum bactericidal agent, protected experimental animals from the lethal effects of Escherichia coli and Bacteroides fragilis endotoxin. Taurolin also prevented the pyrexic response of rabbits to TAB vaccine. Results suggest that Taurolin exerts its antiendotoxic effect by direct reaction with the endotoxin molecule.
Noxythiolin (Noxyflex, Geistlich), given intraperitoneally as a 2.5 per cent solution, protected mice from the lethal effects of an intraperitoneal injection of Escherichia coli. Povidone-iodine (Pevidine, Berk), containing 0.075 per cent iodine, gave no protection.
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