Two accurate, reliable, and highly sensitive spectrofluorometric methods were developed for simultaneous determination of the binary mixture of Atorvastatin and Ezetimibe without prior separation steps. The first method is based on double scan synchronous fluorescence spectrometry. Each of Atorvastatin and Ezetimibe can be determined independent of the other when scanned at Δλ 100 nm and 40 nm, respectively. The relative fluorescence intensity-concentration plots at two wavelengths, 272 (Δλ 100 nm) and 266 nm (Δλ 40 nm) were rectilinear over the range of 0.4-8 µg/mL (for Atorvastatin) and 0.6-8 µg/mL (for Ezetimibe), respectively. The second method is based on the technique of simultaneous equations (Vierodt's method), in which two equations are solved simultaneously after using a single excitation wavelength of 273 nm and λ Em1 380 nm of Atorvastatin and λ Em2 301 nm of Ezetimibe. Under the optimum conditions, linear relationships were found between the relative fluorescence intensity and the concentrations of the investigated drugs in the range of 0.4-8 µg/mL (for Atorvastatin) 0.6-8 µg/mL (for Ezetimibe). The different experimental parameters affecting the fluorescence intensities of the two drugs were carefully studied and optimized. The proposed methods were successfully applied for the determination of the investigated drugs in pure form, dosage form and in synthetic mixtures with good recovery and the results obtained were favorably compared to those obtained with a reference method.Key words Atorvastatin; Ezetimibe; synchronous fluorescence spectrometry; Vierodt's method Atorvastatin calcium (ATV), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a lipid regulating drug used to reduce low density lipoprotein (LDL)-cholesterol, apolipoprotein B and triglycerides, and to increase high density lipoprotein (HDL)-cholesterol in the treatment of hyperlipidaemias (Fig. 1a). It is also used for prophylaxis of cardiovascular events in patients with multiple risk factors including diabetes mellitus. ATV is a member of the drug class known as statins.
1)Ezetimibe (EZE) is an inhibitor of intestinal absorption of cholesterol and plant sterols (Fig. 1b). It prevents transport of cholesterol through the intestinal wall by selectively blocking the absorption of cholesterol from dietary and biliary sources. This reduces the overall delivery of cholesterol to the liver, thereby promoting the synthesis of LDL receptors and a subsequent reduction in the serum LDL-C.2) Combining the different mechanisms of action of these agents appears to provide substantial reductions in LDL-C, with additional favorable changes in total cholesterol, triglycerides, and HDL-C. Clinical studies have shown that co-administration of EZE plus ATV was significantly more effective at reducing LDL-C concentrations than EZE or ATV alone.3) There is an urgent need to develop analytical methods for the simultaneous analysis of EZE and ATV in pharmaceutical dosage forms due to the continuous increase in clinical use of these t...