ISSN:
0899-0042
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
SL 84.0418 is a new antihyperglycaemic drug. It is an orally active and selective α2-adrenoceptor antagonist. This molecule, a pyrroloindole derivative, contains an asymmetric center yielding two enantiomers. In order to evaluate the pharmacokinetic profile of both enantiomers following oral administration of the racemate we have developed an HPLC method for their separation and quantification. The liquid - liquid extraction involved three steps with two salting-out procedures at pH 11.5 before and after a back-extraction with 0.005 M H2SO4. The enantiomers were separated by HPLC on a stainless-steel column (100 x 4.0 mm) packed with a chiral α1 -acid. The UV response was linear from 1 to 250 ng/ml for both enantiomers. The relative standard deviation (RSD) for reproducibility was below 10.7%. Using quality control samples, precision was found below 7.8% and accuracy was 108%. Extraction recoveries were ca. 60% for both enantiomers and 94% for the internal standard. Column life was brought up to 2 months, which corresponds to about 1,000 injections of biological extract. No guard column was used, but a daily back-flush was carried out. This method is suitable for routine analysis and 30 to 40 plasma samples a day can be processed. This method allows the definition of the pharmacokinetic profile of both enantiomers of SL 84.0418 in human plasma after single oral administration of doses as low as 20 mg of the racemic drug.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chir.530040209
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