ISSN:
1052-9306
Keywords:
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A chemical ionization gas chromatographic mass spectrometric assay is described for ethyl loflazepate (CM 6912), a new benzodiazepine with a potent anti-anxiety activity, and two of its metabolites in plasma and urine. The parent drug was separated from the biological samples by simple extraction at pH 9. In all samples analysed, parent drug levels were below the detection limit, confirming its extensive biotransformation at the sites of absorption and during its first pass through the liver. Pharmacokinetic data were obtained by measuring the total levels of two of the major metabolites. Accurate data may not be obtained for both metabolites separately since one of them (M1) is chemically transformed to metabolite M2 during plasma sampling, storage and extraction. Their total levels were measured after complete degradation of the unstable metabolite and extraction of the sample at pH9. The precision and accuracy of this method are better than 10% in the low ng range. The detection limit is 1 ng m1-1. Pharmacokinetic data were obtained from human volunteers given a single oral dose of 2 mg CM 6912 in tablet form. Cp max values ranged from 30 to 55 ng ml-1 and were reached within 1.5 to 3 h after administration. Following the achievement of peak levels the concentration declined with an apparent biexponential pattern showing an elimination half-life ranging from 51 to 103 hours in its terminal phase.
Additional Material:
12 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/bms.1200071124
Permalink
