title: Quantitative determination of fluvastatin in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry using [18O2]-fluvastatin as an internal standard.
abstract: A sensitive and specific method for the quantitative determination of fluvastatin in human plasma is presented. The drug was isolated from plasma by extractive alkylation with pentafluorobenzyl bromide and further derivatized to the bis-trimethylsilyl derivative. [18O2]-Fluvastatin was prepared from unlabelled fluvastatin and used as an internal standard. Gas chromatography/mass spectrometry under negative ion chemical ionization conditions was used for quantitative measurement of the drug, using m/z 554.26 and 558.26 for target and internal standard, respectively. Calibration graphs were linear within a range of 2 and 512 ng mL(-1) plasma. Intra-day precision was 0.94% (2 ng mL(-1)), 2.53% (8.2 ng mL(-1)), 2.16% (81.9 ng mL(-1)) and 3.26% (409.6 ng mL(-1)); inter-day variability was found to be 1.64% (2 ng mL(-1)), 0.97% (8.2 ng mL(-1)), 1.97% (81.9 ng mL(-1)) and 2.01% (409.6 ng mL(-1)). Intra-day accuracy showed deviations of 0.6% (2 ng mL(-1)), 0.37% (8.2 ng mL(-1)), -1.52% (81.9 ng mL(-1)) and -1.67% (409.6 ng mL(-1)); inter-day accuracy was of -1.64% (2 ng mL(-1)), -1.13% (8.2 ng mL(-1)), -2.28% (81.9 ng mL(-1)) and -0.46% (409.6 ng mL(-1)). The stable isotope labelled standard was found to be stable under the analytical conditions.
authors.affiliation: University Children's Hospital, Division of Analytical Biochemistry and Mass Spectrometry, Auenbruggerplatz 30, A-8036 Graz, Austria. hans.leis@meduni-graz.at
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Leis
authors.forename: Werner
authors.initials: W
authors.lastname: Windischhofer
mesh_terms: D002138:Calibration; D005229:Fatty Acids, Monounsaturated / Q000097:blood*; D000077340:Fluvastatin; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood*; D007211:Indoles / Q000097:blood*; D007553:Isotope Labeling; D010103:Oxygen Isotopes / Q000097:blood; D012015:Reference Standards; D012680:Sensitivity and Specificity
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D010103:Oxygen Isotopes; D000077340:Fluvastatin