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.
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ABSTRACT: Simple, accurate and reliable kinetic spectrophotometric method for the determination of fluvastatin sodium (FVS) in pure form and pharmaceutical formulations has been described. The method is based on the formation of colored product between FVS and 4-chloro-7-nitrobenzofurazan (NBD-Cl) in acetone medium at 55 ± 2ºC. The reaction is followed spectrophotometrically by measuring the increase in absorbance at 462 nm as a function of time. The rate data and fixed time methods were adopted for constructing the calibration curves. The linearity ranges were found to be 15.0-50.0 and 10.0-90.0 μg mL-1 for rate data and fixed time methods, respectively. The limit of detection for rate data and fixed time methods is 0.017 and 0.134 μg mL-1, respectively. The proposed methods have been successfully applied to the determination of fluvastatin sodium in pharmaceutical dosage forms with no interference from the excipients. Statistical comparison of the results shows that there is no significant difference between the proposed and official methods.International Journal of Biomedical Science. 01/2011;
Article: Spectroscopic and chromatographic determination of fluvastatin sodium in presence of its acid degradate[show abstract] [hide abstract]
ABSTRACT: Six new selective and precise methods were developed and validated for the determination of fluvastatin sodium (Flu) in pure form, in presence of its acid degradate and in pharmaceutical formulations. The degradate was isolated, via acid degradation, characterized and confirmed. The first method was a third derivative (3D) method which allows the determination of Flu at 318.6 nm (zero-crossing of its acid degradate) over the concentration range of 4 – 20 μg.mL-1 for Flu. The second and third methods were first and second derivative ratio techniques (1DD and 2DD). The measurements were taken at 240.4 nm (1DD240.4), 259.4 nm (1DD259.4), 294.8 nm (1DD294.8) (1DD method), at 250.4 nm (2DD250.4) and at 264.2 nm (2DD264.2) (2DD method) over the concentration range 4 – 20 μg.mL-1, for Flu, (1DD and 2DD methods), using normalized spectra as divisors. The fourth method was a sensitive spectrofluorimetric method which was based on measuring the native fluorescence intensity of FLU in ethanol at 776 nm with excitation at 258 nm, over the concentration range of 1 – 10 μg.mL-1. The fifth method was based on separation of Flu from its acid degradate followed by densitometric measurements of the spots at 304 nm. The separation was carried out on silica gel F254 plates using chloroform : hexane : methanol : glacial acetic acid (5 : 5 : 1 : 1, v/v/v/v) as developing system. This method allows the determination of FLU over a concentration range of 1 – 10 μg/spot with mean percentage recovery 100.07 ± 0.935. The sixth method was based on high performance liquid chromatographic (HPLC) separation of Flu from its acid degradate on reversed phase Zorbax C18 column, using methanol : water (80 : 20, v/v) as mobile phase at a flow rate of 1 mL.min-1 and sodium benzoate was used as internal standard (IS) with UV detection at 242 nm. Linear relationship was obtained over the concentration range of 5 – 50 μg.mL-1. The selectivity of the proposed methods was checked using laboratory prepared mixtures and satisfactory results were obtained. The proposed methods have been successfully applied to the analysis of FLU in pharmaceutical dosage form and the validity of these methods was ascertained by applying the standard addition technique. The results were statistically compared with the reported USP method and no significant difference was found with respect to both precision and accuracy. Five of the suggested methods have the advantage of being stability indicating. Therefore, they can be used for routine analysis of the drug in quality control laboratories.Int J. PharmTech Res. 01/2010; 2:875-898.