Determination of 7 Related Substances in Abemaciclib Active Pharmaceutical Ingredient by LC-MS/MS

OBJECTIVE  To establish an LC-MS/MS method for the determination of 7 related substances in abemaciclib active pharmaceutical ingredient.

METHODS A liquid chromatography-triple quadrupole mass spectrometer was adopted. An Agilent ZORBAX Eclipse Plus C₁₈(2.1 mm×100 mm, 1.8 μm) column was used. Mobile phase A was 0.01 mol·L⁻¹ ammonium formate solution(pH adjusted to 9.0 with ammonia water), and mobile phase B was acetonitrile. Gradient elution was performed at a flow rate of 0.3 mL·min⁻¹ with the column temperature set at 40 ℃. Electrospray ionization source was applied, and detection was carried out in positive ion mode combined with multiple reaction monitoring.

RESULTS The linear range of impurity Ⅴ with genotoxic alerting structure was 0.10−9.76 ng·mL⁻¹(r=0.99948). The linear range of impurity Ⅰ, Ⅱ, Ⅲ, Ⅳ, Ⅵ and Ⅶ were 19.44−583.08 ng·mL⁻¹(r=0.99930), 19.53−586.00 ng·mL⁻¹(r=0.99975), 22.26−667.92 ng·mL⁻¹(r=0.99929), 20.75−622.64 ng·mL⁻¹(r=0.99902), 20.52−615.65 ng·mL⁻¹(r=0.99971), 21.17−635.04 ng·mL⁻¹(r=0.99705), respectively. The RSD values of precision and repeatability tests were all <3%; The average recovery rate of impurity Ⅴ was 94.8%(RSD=4.06%), while the average recoveries of the other 6 impurities ranged from 94.9% to 97.4%, with RSD values between 0.16% and 3.65%.

CONCLUSION The established LC-MS/MS method possesses high accuracy, good sensitivity and strong specificity, which can provide a reference for the quality control of abemaciclib active pharmaceutical ingredient.