Chiral Separation of Atorvastatin Calcium and Its Enantiomeric Impurity by Supercritical Fluid Chromatography / 中国药学杂志

ABSTRACT

OBJECTIVE: To develop a supercritical fluid chromatography method for the separation of atorvastatin calcium and its enantiomer, meanwhile assaying the enantiomer. METHODS: Atorvastatin calcium and its enantiomer were separated on a ACQUITY UPC2 Trefoil CEL2 column(3.0 mm×150 mm, 2.5 μm) maintained at 45 ℃ with the mobile phase containing a mixture of CO2 and methanol with 0.1% TFA(78∶22, V/V) at 1.5 mL·min-1, and the detection wavelength was set at 244 nm. The back pressure was set at 13.8 MPa. RESULTS: The enantiomer and atorvastatin calcium were separated successfully in 5 min with a resolution factor of 4.1. Good linear relationship was established between the peak response and the concentration in the range of 2.5-50 μg·mL-1 for enantiomer(r2=0.999 9, n=6), the quantitative limit(S/N=10) was 2.5 μg·mL-1, and the detection limit(S/N=3) was 1.0 μg·mL-1. The spiked recovery of the enantiomer was 100.40%(n=9). CONCLUSION: The proposed method shows high accuracy, repeatability and stability. It can be employed for the quality control and stability research of the enantiomer of atorvastatin calcium.