Quality Studies For Palbociclib

Palbociclib（PD）is an oral selective inhibitor of cyclin-dependent kinase（CDK）4 and 6,which can restore the control of cell cycle and block the proliferation of tumor cells.In February 2015,palbociclib was approved by the accelerated approval process of the US FDA,and indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor（ER）-positive,human epidermal growth factor receptor（HER-2）-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.In this paper,the quality study of the palbociclib raw materials had been completed.Finally,the quality standard was formulated.First,a high performance liquid chromatography（HPLC）method for analyzing rawmaterial PD-4、PD-9 and drug intermediate PD-10、PD-11 related substances were established,we have determined the quality standard.And the palbociclib raw materials were researched.The characters of them were investigated.UV and IR spectrophotometry,and High Performance Liquid Chromatography were respectively established to identify them.The content,related substances,loss on drying,heavy metals,residual solvent and other projects were checked.The stability of palbociclib was also researched.These results were symbolized pharmacopoeia and related quality standards.A simple and efficient HPLC method was developed for quality control of the related substances.Agilent HC C₁₈column was used with the mobile phase of gradient elution,and the flow rate was 1.0 m L/min,The detection wavelength is 250 nm,the column temperature was 40°C and the injection volume was 10μL.Palbociclib and the impurities A,B,C,D,raw material PD-9 and Intermediate PD-10 were detected.These results showed that the separation of palbociclib peak and impurities peaks were respectively greater than 1.5,which the determination of related substances were not interfered by blank solvent.Good linearity,specificity,precision,durability and high degree of accuracy were detected in the test,the sample is stable within 24 hours.Therefore,the methods can be used to control the related substances of palbociclib.In addition,the chromatographic conditions for the determination of raw material drug for palbociclib by high performance liquid chromatography were also established.Agilent HC C₁₈column was used with the mobile phase of isocratic elution,and the flow rate was1.0 m L/min,at the detection wavelength of 234 nm,the column temperature was 40°C and the injection volume was 10μL.These results showed that the blank solvent did not interfere the determination of palbociclib.The calibration curve of palbociclib was linear in the concentration range of 0.05mg/m L-0.15mg/m L and R²=0.9999.The RSD was less than 2.0%of the precision,accuracy and stability test.Finally,the stability of palbociclib of the raw materials was investigated.These results showed that there were no significant changes for the traits,loss on drying,assay and the related substances of the three batches of palbociclib raw materials in the accelerated conditions and long-term conditions.The quality standard of the palbociclib was scientific and reliable,having the practical significance.