Cinetica quimica

InternatIonal journal of BIomedIcal scIence

ORIGINAL ARTICLE

Kinetic Spectrophotometric Determination of Fluvastatin in Pharmaceutical Preparations
Safwan Ashour1, Mahmoud Bahbouh2, Mouhammed Khateeb2
1 2

Department of Chemistry, Faculty of Sciences, University of Aleppo, Aleppo, Syria; Department of Chemistry, Faculty of Sciences, University of Al-Baath, Homs, Syria

AbstrActSimple, 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 inabsorbance 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 successfullyapplied 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. (Int J Biomed Sci 2010; 6(1):19-26) Keywords: fluvastatin; kinetic spectrophotometry; 4-chloro-7-nitrobenzofurazan (NBD-Cl); pharmaceutical dosageforms; method validation

INtroDuctIoN
Fluvastatin sodium (FVS) is (3R,5S,6E)-rel-7-[3-(4fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl]-3,5-dihyroxy-6-heptenoicacid, monosodium salt, is a competitive inhibitor of HMG-CoA reductase, which is responsible for the conversion of 3-hydroxy-3- methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, a precursor of sterols including cholesterol. It is used toreduce triglycerides, LDL-cholesterol, apoliporotein B and to increase HDLcholesterol, in the treatment of hyperlipidaemias including

Corresponding author: Safwan Ashour, Department of Chemistry, Faculty of Sciences, University of Aleppo, Aleppo, Syria. Tel: 00963-933604016; E-mail: profashour@myway.com. Received September 10, 2009; Accepted november 13, 2009

hypercholesterolaemias and combinedhyperlipidaemia. FVS is metabolized in the liver, primarily via hydroxylation of the indole ring at the 5 and 6-positions. N-dealkylation and beta-oxidation of the side-chain also occurs. The hydroxyl metabolites have some pharmacological activity, but do not circulate in the blood. FVS has two optical enantiomers, an active 3R, 5S and an inactive 3S, 5R form. FVS is 98% bound to plasma proteins(1-3). Literature survey reveals that FVS is official in U.S.P. (4). Several electroanalytical methods are available for the determination of the latter compound by differential plus voltammetry (5), square-wave adsorptive-stripping voltammetry (SWAdSV) (6) in pharmaceutical preparations, cyclic voltammetry (7) and variety of voltammetric techniques (8) in pharmaceutical dosage forms andbiological fluids. FVS has been determined by capillary electrophoresis (CE) (9), first derivative spectrophotometry

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Int J Biomed Sci

vol. 6 no. 1

March 2010

19

KInetIc sPectroPHotometrIc determInatIon oF FluVastatIn

(10), High performance liquid chromatography (HPLC) with fluorescence detector (11-16) and ultraviolet detector (17, 18), Liquid chromatography/negativeion electrospray tandem mass spectrometry (19), Liquid chromatography/ electrospray mass spectrometry (20), and gas chromatography/negative ion chemical ionization mass spectrometry (21) in pharmaceutical formulations and biological samples. No kinetic spectrophotometric methods have been reported in the literature for the assay of FVS. Some specific advantages that the kinetic methods possess are...