Objective: To develop the HPLC-DAD/MS method for the determination of related substances in simvastatin capsules,including the validation of known impurities A,B,C,D,E,F and G and the attribution analysis of related substances in the product. Methods: The analysis was performed on a C18 column (33 mm×4.6 mm,3 μm) with mobile phases A (acetonitrile-0.1% phosphoric acid solution,50: 50) and B (0.1% phosphoric acid in acetonitrile) by gradient elution at the flow rate of 3.0 mL·min-1,and the detection wavelength was set at 238 nm. Results: Simvastatin was separated completely from known impurities and degradation products under various conditions with the purity factor greater than 999.0.Simvastatin and impurities A,B,C,D,E,F,G revealed good linearities over the ranges of 0.7924-39.62 μg·mL-1 (r=1.000),0.3118-6.236 μg·mL-1 (r=0.9999),0.3204-6.408 μg·mL-1 (r=0.9999),0.3016-6.032 μg·mL-1 (r=1.000),0.3296-6.592 μg·mL-1 (r=1.0000),0.2032-4.064 μg·mL-1 (r=0.9997),0.2056-4.112 μg·mL-1 (r=0.9999),0.3232-6.464 μg·mL-1 (r=0.9999),respectively.The average recoveries of the above impurities were 101.9%,102.2%,99.8%,102.9%,98.8%,101.5%,99.2%,respectively.Sampling precision,repeatability and intermediate precision all met the requirements and the blank test showed no interference.The limits of quantification of simvastatin and impurities A,B,C,D,E,F,G were 0.20,0.78,0.80,0.60,1.01,0.51,0.62,0.65 ng and the relative correction factors were 1.07,1.06,1.06,2.84,0.97,0.96,1.00,respectively.Conclusion: This method can be used for the determination of simvastatin and its preparations by methodological validation.
