Structural Characterization And Quantitative Analysis Of The Polymorphic Drug Palbociclib

Palbociclib is an oral cyclin-dependent kinase(CDK)4/6 inhibitor.It plays a role in the phosphorylationofretinoblastomaproteinby inhibiting CDK4/6.Palbociclibcan prevent cell from growing to DNA replication and blocking cell DNA synthesis.Palbociclib combined Letrozole for estrogen receptor(ER+)and human epidermal negative factor receptor 2(HER2)-ofthe first-line therapy for postmenopausal women with advanced breast cancer.Compared with the previous two generations of CDKs inhibitors,Palbociclib is highly active and selective in CDK4/6 and with a wide range of clinical application prospects.At present,the polycrystalline structure of Palbociclib includes crystal type A and crystal type B,in which A is stable and is considered to be an effective crystal of anticancer drugs.But palbociclibpreparation process is relatively complex,if improper control of conditions during preparation,drug often exist in mixed crystal or amorphous form,so it is necessary to establish a quantitative analysis methods to ensure drug quality.This paper firstly conducts a qualitative analysis of Palbociclib by elemental analysis(EA),mass spectrometry(MS),scanning electron microscope(SEM),Fourier transform infrared spectroscopy(FT IR),X-ray powder diffraction(PXRD)and differential scanningcalorimetry(DSC).Then the method of single-peak and K-value method was used to quantitatively analyze the palbociclib crystal type A and crystal type B.The results showthat the standard curve establishedby unimodal methodshows a good linear relationship(R2=0.995 and R2=0.9903).The value of K was 0.1571 by the calculation of the palbociclib type A and the reference material,?-Al2O3.Finally,the single peak method and k-value method are verified by means of accuracy,precision,sensitivity and practical application.The results showthat the accuracy of single peak method are higher than K value method,which can be used for actual detection.The research work done in this paper can quickly and accurately identify the palbociclib crystal type A and crystal type B,and make quantitative analysis of it,which has certain theoretical and practical significance.