Sensitive, high-throughput gas chromatographic-mass spectrometric assay for fluoxetine and norfluoxetine in human plasma and its application to pharmacokinetic studies.
A sensitive, robust gas chromatographic-mass spectrometric assay suitable for use in pharmacokinetic or bioequivalence studies is presented for the selective serotonin reuptake inhibitor, fluoxetine, and its major metabolite, norfluoxetine (N-desmethylfluoxetine). This method employs solid-phase extraction followed by acetylation with trifluoroacetic anhydride and analysis of the derivatives using selected ion monitoring. The lower limit of quantification was 1.0 ng/ml, and the assay was linear for both analytes from 1 to 100 ng/ml. Mean recoveries following solid-phase extraction at concentrations of 5.0, 20 and 100 ng/ml were 91% (fluoxetine) and 87% (norfluoxetine). Assay precision (as mean RSD) and accuracy (as mean relative error) for both analytes were tested at the same three nominal concentrations and were found to be within 10% in all cases. Analysis of fluoxetine concentrations in plasma samples from 18 volunteers following administration of a single 40 mg dose of fluoxetine provided the following pharmacokinetic data (mean+/-SD): Cmax, 32.73+/-9.21 ng/ml; AUC0-infinity, 1627+/-1372 ng/ml h; Tmax, 3.08 h (median); ke, 0.022+/-0.007 h(-1); elimination half-life, 37.69+/-21.70 h.
Addison
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RS
Centre for Studies in Drug Disposition, Department of Medicine, The University of Queensland, Royal Brisbane Hospital, Australia.
Franklin
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ME
Hooper
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WD
D000328:Adult; D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D012680:Sensitivity and Specificity; D017367:Selective Serotonin Reuptake Inhibitors
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; C036139:norfluoxetine