These instruments demonstrated similar results for evaluating ADRs in the ICU retrospectively, suggesting that instrument selection with any of the three instruments is reasonable. For concurrent ADR evaluations, there is greater variability in the level of causality obtained among pharmacovigilance algorithms and Kramer displayed better agreement with its comparators. A suggestion for a more definitive concurrent ADR assessment is to use more than one algorithm. This may be challenging in daily clinical practice; however, it is a reasonable expectation for research.
These instruments demonstrated similar results for evaluating ADRs in the ICU retrospectively, suggesting that instrument selection with any of the three instruments is reasonable. For concurrent ADR evaluations, there is greater variability in the level of causality obtained among pharmacovigilance algorithms and Kramer displayed better agreement with its comparators. A suggestion for a more definitive concurrent ADR assessment is to use more than one algorithm. This may be challenging in daily clinical practice; however, it is a reasonable expectation for research.
NOTES P35 cmxom G273 .'I Acid degradation of flavonoids as an aid in their identification In the course of previous studies of constituents from L.&x needlesl~ 2, small quantities of flavonol glycosides were hydrolysed according to standard procedure&a in ethanolic or aqueous HCl. In many cases, especially when very low concentrations were used, partial or complete degradation of the aglycone occurred, even when the time of hydrolysis was restricted to 5 min. Autosidation of flavonols under acid conditions, leading to a benzoic acid, phloroglucinol (phloroglucinol carbosylic acid) and carbon monoxide, has been describedb-7. The rate of autoxidation in I iV WC1 at IOO o given, however, is much lower than that found in our experiments, This is probably due to the concentration used; higher concentrations of the flavonol glycosides produced under similar conditions a reasonable yield of the aglycone. Knowing the effect of autosidation, it may either be prevented by working under an inert atmosphere (nitrogen) or it may be used as a method of identification of the aglycone. In several cases, identification of the benzoic acid(s) obtained from acid degradation provided useful information on the purity and identity of the corresponding aglycone. The glycosides of isorhamnetin and syringetin, for example, proved difficult to separates** and the aglycones differ only in their RF in phenol3. One of the compounds, isolated in low quantity from needles of Larix Zaricina, WCI.S identified as isorhamnetin-3-glucoside by chromatographic and spectral studies. Among the products of acid degradation, however, vanillic acid, as well as syringic acid was found, indicating the presence of a syringetin glycoside; this was later isolated and identified as syringetin-3-glucoside. Obviously, even in phenol, iso-rhamnetin and syringetin were kept at the same spot with RF similar to that of the reference isorhamnetin. Acid degradation followed by identification of the benzoic acid residue(s) has now been introduced as a standard procedure in our laboratory. Chromatography on paper with benzene-acetic acid-water (125 : 72 : 3) proved very useful in this connection, because this solvent system separates both the benzoic acids and the flavonols well, and at the same time indicates the number of hydroxyl groups"gxa. Of course, a similar effect can be obtained by alkaline degradation. Acidic procedures, however, often provide information on the original aglycone, the benzoic acid produced and the sugar residues, and therefore seem much more suited for work on very small samples.
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