Chiral separation of ezetimibe and R-enantiomer by supercritical fluid chromatography / 中国药学杂志

ABSTRACT

OBJECTIVE: To develop an isocratic supercritical fluid chromatography method for the separation of ezetimibe and its R-enantiomer. METHODS: Ezetimibe and its R-enantiomer were separated on a Chiralcel OD column (4.6 mm × 250 mm, 10 μm) maitained at 35℃ with the mobile phase containing a mixture of CO2 and methanol with 0.1% TFA-0.1% TEA (90:10, V/V) at 3.0 mL · min-1, and the detection wavelength was set at 235 nm. The back pressure of SF-CO2 was set at 15 MPa. RESULTS: The R-enantiomer and ezetimibe were separated successfully in 15 min with a resolution factor of 1.6. Good linear relationships were established between the peak response and the concentration in the range of 0.010-0.100 mg · mL-1 for each analyte(r =0.999 9 and 0.999 9, respectively, n =7), the quantitation limits (S/N = 10) were 34 and 32 ng, and the detection limits (S/N =3) were 10 and 9 ng, respectively. The spiked recovery of R-enantiomer of ezetimibe was 98.4% (n =9). CONCLUSION: The proposed method shows high accuracy, repeatability and stability. It could be employed for the quality control and stability research of R-enantiomer of ezetimibe and its tablet formulation.