药物帕博西尼的定性和定量分析研究
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摘要
采用差示扫描量热分析法(differential scanning calorimetry, DSC)、扫描电子显微镜法(scanning electron microscopy, SEM)和X-射线粉末衍射法(X-ray powder diffraction, PXRD)对帕博西尼进行了结构表征,初步建立了帕博西尼A、B两种晶型的鉴定方法;通过X-射线粉末衍射单峰法(峰面积法和峰高法)对帕博西尼(palbociclib)有效晶型A中混杂的晶型B进行了定量测定。结果表明:DSC法鉴定两种晶型其结果区分不够明显, SEM法和PXRD法可快速有效鉴别两种晶型;峰面积法和峰高法所建立的标准曲线方程分别为y=0.842 75x-0.001 21和y=0.909 64x-0.002 32,两种方法的R~2值分别为0.986 17和0.985 83,两组曲线均取得了较好的线性关系,其中峰面积法的线性关系更好。峰面积标准曲线计算出B晶型的检测限(limit of detection, LOD)和定量限(limit of quantity,LOQ)分别为1.17%和3.92%,峰高标准曲线计算出B晶型的检测限和定量限分别为1.19%和3.97%,峰面积法更为灵敏。采用本实验的方法可快速的鉴定帕博西尼晶型A和晶型B并对其进行定量测定。
In this paper, three methods, differential scanning calorimetry(DSC), scanning electron microscopy(SEM) and X-ray powder diffraction(PXRD), were used to characterize the structure of Palbociclib. The form-B crystal mixed in with form-A crystal, the effective form of Palbociclib, was quantitated by the single peak method(peak area method and peak height method) using X-ray powder diffraction. While the qualitative identification by DSC was not clear, SEM and PXRD quickly and effectively identified two types of crystal. The standard curve equations established by the peak area method and the peak height method are: y = 0.842 75 x-0.001 21 and y = 0.909 64 x-0.002 32. This suggests that the linear relationship of peak area method is better than that of peak height method(R~2= 0.986 17 and R~2= 0.985 83). The sensitivity of the peak area method(LOD = 1.17%, LOQ =3.92%) are higher than the peak height method(LOD = 1.19%, LOQ = 3.97%). The methods from this study can be used to identify and quantify palbociclib form-A and form-B crystal rapidly.
In this paper, three methods, differential scanning calorimetry(DSC), scanning electron microscopy(SEM) and X-ray powder diffraction(PXRD), were used to characterize the structure of Palbociclib. The form-B crystal mixed in with form-A crystal, the effective form of Palbociclib, was quantitated by the single peak method(peak area method and peak height method) using X-ray powder diffraction. While the qualitative identification by DSC was not clear, SEM and PXRD quickly and effectively identified two types of crystal. The standard curve equations established by the peak area method and the peak height method are: y = 0.842 75 x-0.001 21 and y = 0.909 64 x-0.002 32. This suggests that the linear relationship of peak area method is better than that of peak height method(R~2= 0.986 17 and R~2= 0.985 83). The sensitivity of the peak area method(LOD = 1.17%, LOQ =3.92%) are higher than the peak height method(LOD = 1.19%, LOQ = 3.97%). The methods from this study can be used to identify and quantify palbociclib form-A and form-B crystal rapidly.
引文
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[15]Yang XP.The development and application of X-ray diffraction[J].J Shanxi Norm Univ(山西师范大学),2007,21:72-76.
[16]Lu J,Fu LY,Wang X.Discussion on the detecting methods for limit of detection and limit of quantification in validation of analytical method[J].Drug Stand China(中国药品标准),2012,13:33-35.
[2]Zheng Y,Wu C,Zhang M.The epidemic and characteristics of female breast cancer in China[J].China Oncol(中国癌症杂志),2013,23:561-569.
[3]Cicenas J,Kalyan K,Sorokinas A,et al.Highlights of the latest advances in research on CDK inhibitors[J].Cancers,2014,6:2224-2242.
[4]Chekal BP.Solid forms of a selective CDK4/6 inhibitor:US,WO2014/128588[P].2014-08-28.
[5]Bell T,Crown JP,Lang I,et al.Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as firstline treatment[J].Curr Med Res Opin,2016,32:959-965.
[6]Finn RS,Grown JP,Lang I,et al.The cyclin-dependent kinase4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptorpositive,HER2-negative,advanced breast cancer(PALOMA-1/TRIO-18):a randomised phase 2 study[J].Lancet Oncol,2015,16:25-35.
[7]Liu S,Xu J,Cui Y,et al.Palbociclib-a new drug approved for advanced breast cancer[J].Prog Pharm Sci(药学进展),2015,39:634-640.
[8]Tempka D,Tokarz P,Chmielewska K,et al.Downregulation of PARP1 transcription by CDK4/6 inhibitors sensitizes human lung cancer cells to anticancer drug-induced death by impairing OGG1-dependent base excision repair[J].Redox Biol,2018,15:316-326.
[9]Fang H,Huang D,Yang F,et al.Potential biomarkers of CDK4/6inhibitors in hormone receptor?positive advanced breast cancer[J].Breast Cancer Res Treat,2018,168:287-297.
[10]Liu M,Liu H,Chen J.Mechanisms of the CDK4/6 inhibitor palbociclib(PD 0332991)and its future application in cancer treatment[J].Oncol Rep,2018,39:901-911.
[11]Wang SS,Yu HY.Palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor positive,HER2 negative,advanced breast cancer significantly improve progression-free survival[J].J Evid Based Med(循证医学),2015,15:146-148.
[12]Zhao YN,Chen XQ,Zhu K,et al.Thermostability and crystal structure of anticancer drug dasatinib[J].Acta Pharm Sin(药学学报),2011,46:1104-1107.
[13]Huang R,Wang T,Yang X,et al.Characterization of taste-masking dry emulsion of azithromycin by in vitro and in vivo evaluation[J].Acta Pharm Sin(药学学报),2017,52:795-801.
[14]Li G,Su GQ,Xu QW,et al.A new crystal form of nateglinide[J].Acta Pharm Sin(药学学报),2001,37:532-534.
[15]Yang XP.The development and application of X-ray diffraction[J].J Shanxi Norm Univ(山西师范大学),2007,21:72-76.
[16]Lu J,Fu LY,Wang X.Discussion on the detecting methods for limit of detection and limit of quantification in validation of analytical method[J].Drug Stand China(中国药品标准),2012,13:33-35.