Determination of flurazepam and its major metabolites N-1-hydroxyethyl- and N-1-desalkylflurazepam in plasma by capillary gas chromatography
Salama, Z.; Schraufstetter, B.; Jaeger, H.
Arzneimittel-Forschung 38(3): 400-403
1988
ISSN/ISBN: 0004-4172 PMID: 3382464 Document Number: 310225
In the present paper we describe a method for the quantitative determination of flurazepam (I) and two of its metabolites, N-1-desalkylflurazepam (II) and N-1-hydroxyethylflurazepam (III), in serum after therapeutic dosings is described. The method is sensitive (lower limit of quantification for I and III: 1 ng/ml, for II: 2 ng/ml), selective and--compared to the analytical approaches already published--simple to handle. Thus this assay is well suitable for determinations during clinical studies (e.g. evaluating the pharmacokinetics, bioavailability/bioequivalence). Following simple extraction- and derivatization steps (the latter being only required for III) the extract is injected directly onto a fused-silica, bonded-phase capillary column of a gas chromatograph and the compounds of interest detected by an electron-capture detector (ECD). The assay has been used successfully during several clinical studies, especially as very low dosages result in also very low blood concentrations.