Ribociclib succinate

Ribociclib succinate (CAS No. 1374639-75-4) is a selective cyclin-dependent kinase 4/6 (CDK4/CDK6) inhibitor. Its core bioactivity is to inhibit the proliferation of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer cells, and it is commonly used in combination with endocrine monotherapy or aromatase inhibitors; the limit of detection (LOD) of its analytical method is 1.53 μg/mL and the limit of quantification (LOQ) is 4.66 μg/mL; commonly used application concentrations: in vitro analytical linear range 0.1–150 μg/mL. In weak solubility experiments, the solubility in a simulated gastric environment (pH 1.2, FaSSGF buffer) is 814.05 μg/mL, the solubility in an intestinal environment (pH 6.5, FaSSIF buffer) is 494.71 μg/mL, and the solubility at pH 6.8 is 463.20 μg/mL. The experimental dose is calculated based on a clinically equivalent dose of 600 mg/250 mL water; the effective therapeutic concentration corresponds to a clinical oral dose of 600 mg/day (a single dose is a 200 mg film-coated tablet), which can be taken with or without food. Concomitant use with acid-reducing agents does not significantly affect its solubility or absorption, and no dose adjustment is required.

References:

[1] Desai M, Patil PH, Rao RR, Shenoy GG, Rao M, Mutalik S, Jagadish PC. Should the Use of Acid Reducing Agents in Conjunction with Ribociclib be Avoided? An Integrated QbD Approach for Assessment of pH-Mediated Interaction. J Chromatogr Sci. 2024 Feb 2;62(2):175-181. doi: 10.1093/chromsci/bmac084. PMID: 36241222.