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Development and validation of capillary zone electrophoresis method for simultaneous determination of CDK4/6 inhibitors in pharmaceutical dosage forms

Breast cancer is one of the most common cancers in women. Approximately two-thirds of breast cancers are HR+/HER2- tumors [1]. Advances in the treatment of this cancer phenotype have been made with abemaciclib (ABE), ribociclib (RIB), and palbociclib (PAL), inhibitors of cyclin D dependent kinases 4 and 6 (CDK4/6) in combination with aromatase inhibitors letrozole or anastrozole, and selective estrogen receptor degrader fulvestrant [2]. Based on a literature search, there is an unmet need for fast and simple methods for their determination in pharmaceutical dosage forms. Thus, we developed a first capillary electrophoresis method for fast simultaneous analysis of three CDK4/6 inhibitors. Separation was achieved by capillary zone electrophoresis in an acidic medium, in accordance with the structures of analytes and their pKa values. The optimal pH of the running buffer was found to be 2.9. The optimal method conditions were 27.5 kV separation voltage, the temperature of 30 °C, 5 s injection under 50 mbar pressure, and 50 mM phosphate buffer. The developed method was validated according to the ICH guidelines and was shown to be linear in the range of 10 to 100 µg mL-1 with correlation coefficients being 0.9981, 0.9984, and 0.9991 for ABE, RIB, and PAL, respectively. Selectivity of the method was tested by calculating the peak purities and was shown to be acceptable. The robustness of the method was tested by changing applied voltage, temperature, and pH one variable at a time, and the changes in peak areas and migration times were shown to be in the range of 0.22 to 1.63 %. Intra-day and inter- day repeatabilities were acceptable with RSD values in the ranges of 0.22 to 1.08 % and 0.64 to 3.95 %, respectively. The validated method was successfully applied to pharmaceutical dosage forms of all CDK4/6 inhibitors.

capillary electrophoresis ; CDK4/6 inhibitors, breast cancer

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