Abstract
Two sensitive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets. The methods are based on the oxidation of SMT by a measured excess of cerium (IV) in acid medium followed by determination of unreacted oxidant by two different reaction schemes. In one procedure (method A), the residual cerium (IV) is reacted with a fixed concentration of fer- roin and the increase in absorbance is measured at 510 nm. The second approach (method B) involves the reduction of the unreacted cerium (IV) with a fixed quantity of iron (II), and the resulting iron (III) is com- plexed with thiocyanate and the absorbance measured at 470 nm. In both methods, the amount of cerium (IV) reacted corresponds to SMT concentration. The experimental conditions for both methods were opti- mized. In method A, the absorbance is found to increase linearly with SMT concentration (r = 0.9995) whereas in method B, the same decreased (r = -0.9943). The systems obey Beer's law for 0.6-7.5 and 0.5- 5.0 µg mL-1 for method A and method B, respectively. The calculated molar absorptivity values are 2.7 X 104 and 1.06 X 105 Lmol-1 cm-1, respectively; and the corresponding sandel sensitivity values are 0.0153 and 0.0039µg cm-2, respectively. The limit of detection (LOD) and quantification (LOQ) are reported for both methods. Intra-day and inter-day precision, and accuracy of the methods were established as per the current ICH guidelines. The methods were successfully applied to the determination of SMT in tablets and the results were statistically compared with those of the reference method by applying the Student's t-test and F-test. No interference was observed from the common excipients added to tablets. The accuracy and validity of the methods were further ascertained by performing recovery experiments via standard addition procedure.
Highlights
Simvastatin (SMT), chemically known as (1S, 2S, 8S, 8aR)-1,2,6,8,8a-hexahydro-1-(2-((2R, 4R)-terahyro-4-hydroxy-6-oxo-2H-pyran-2-yl)2,6-dimethylnapthalen-8-yl 2,2-dimethylbutanoate (Fig.1) is a cholesterol lowering lactone,and is identified as being among the most widely prescribed drugs in the world in 2007
The present methods entail adding a known excess of cerium (IV) sulphate to SMT in acid medium followed by the determination of unreacted oxidant by two reaction schemes involving the use of ferroin, and iron (II) and thiocyanate as reagents
The decreasing concentrations of cerium (IV) sulphate upon reacting with a fixed concentration of ferroin resulted in increasing absorbance at 510 nm due to the bleaching of ferroin colour by the oxidant, the bleaching being caused by the oxidation of ferroin to ferriin by cerium (IV) sulphate
Summary
Simvastatin (SMT), chemically known as (1S, 2S, 8S, 8aR)-1,2,6,8,8a-hexahydro-1-(2-((2R, 4R)-terahyro-4-hydroxy-6-oxo-2H-pyran-2-yl)2,6-dimethylnapthalen-8-yl 2,2-dimethylbutanoate (Fig.1) is a cholesterol lowering lactone,and is identified as being among the most widely prescribed drugs in the world in 2007. It is found to lower cholesterol by inhibiting the synthesis of movalinic acid, which is a key precursor in cholesterol synthesis. SMT is administered as a prodrug, and in liver, it is hydrolysed to the β-hydroxy acid form [1]. The therapeutic importance of SMT justifies research to develop analytical methods for its determination in body fluids and pharmaceuticals. The most widely used technique for the assay of SMT has been the high performance liquid chromatography (HPLC) with UV, ms-ms or fluorescence detection. The drug in plasma has been assayed by LC
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