Development and validation of a novel CE method for simultaneous analysis of ribociclib, letrozole and ibuprofen

Breast cancer is the most common cancer worldwide while the HR+/HER2- subtype is the most prevalent [1]. Locally advanced or metastatic HR+/HER2- breast cancers are treated with the combination of CDK4/6 inhibitors and drugs with anti-estrogen effects. One of the common combinations used in clinical practice is ribociclib with letrozole [2]. Many breast cancer patients suffer from various comorbidities and side effects. Thus, different drug classes are regularly used in clinical practice, painkiller ibuprofen being one of the most common. Because of that, we developed a capillary electrophoresis (CE) method for the simultaneous determination of ribociclib, letrozole, and ibuprofen since drugs metabolized by the same enzymes can have interactions. During method development, different buffer types (borate and phosphate with and without SDS) and additives and surfactants (SBE-β-CD and i-PrOH) were tested. Separation was achieved with 75 mM phosphate, 8.5 mM sulfobutylether-β-cyclodextrin, and 5% i-PrOH. The optimal conditions were 15 kV, 25 °C and 5 s hydrodynamic injection under 50 mbar. The developed method was validated according to the ICH guidelines and was shown to be linear in the range of 1 to 75 µg mL-1 (r>0.9957). Intra-day and inter-day repeatabilities were evaluated for method precision with acceptable RSD values. The robustness of the method was tested by changing applied voltage (± 0.5 kV), cyclodextrin concentration (± 0.5 mM), and temperature (± 2 ºC) one variable at a time, and the changes in peak areas and migration times were shown to be in the range of 0.34 to 7.27 %. The validated method is the basis for the further development of an even more sensitive method capable of detecting low plasma concentrations of these drugs using innovative sample preparation techniques and coupling to the mass detector which could then be applied to standard clinical practice.