帕博昔布胶囊的制备及其有关物质HPLC检测方法的建立
|
摘要
参考原研的帕博昔布胶囊(Ibrance)说明书中所述辅料,通过正交试验筛选确定了仿制胶囊的最佳处方,即每100粒含:帕博昔布7.5 g,微晶纤维素11 g,一水乳糖5.6 g,羧甲淀粉钠1.59 g,胶态二氧化硅0.265 g,硬脂酸镁0.545 g。以3%羧甲淀粉钠溶液为黏合剂湿法制粒后,60℃干燥整粒,填充胶囊。同时建立了一种新的高效液相色谱法分离和测定帕博昔布中的5种有关物质。采用InertSustain C_(18)柱,以pH 5.7乙酸铵缓冲液∶乙腈为流动相,梯度洗脱,在225 nm下检测。经方法学验证表明,本法专属性强、灵敏度高、耐用性好,可用于帕博昔布产品有关物质的检测和质量控制。
Palbociclib is an inhibitor of CDK4/6 which studied by Pfizer. It is used in the treatment of female patients with ER positive breast cancer clinically. Because of its outstanding effect in clinical trials, the FDA approved its listing only in United States. There are no relevant reports of its preparation yet. Based on the excipients of palbociclib capsules(Ibrance) from Pfizer, the formulation of generic palbociclib capsules was screened by orthogonal test, finally the optimal formulation was as follows: palbociclib 7.5 g, microcrystalline cellulose 11 g, lactose monohydrate 5.6 g, sodium carboxymethyl starch 1.59 g, colloidal silica 0.265 g, magnesium stearate 0.545 g for 100 capsules. During the preparation, 3% sodium carboxymethyl starch solution was used as adhesive for wet granulation, then the granules were dried at 60 ℃ and filled into the capsules. Meanwhile, a novel HPLC method for isolating and detecting five related substances of palbociclib was established. An Inert Sustain C_(18) column was used with ammonium acetate buffer(pH 5.7)∶acetonitrile as mobile phase by gradient elution. The detective wavelength was 225 nm. The method was validated with specificity, sensitivity, and durability. The results indicated that the novel HPLC method could be used for its related substances' analysis and quality control.
Palbociclib is an inhibitor of CDK4/6 which studied by Pfizer. It is used in the treatment of female patients with ER positive breast cancer clinically. Because of its outstanding effect in clinical trials, the FDA approved its listing only in United States. There are no relevant reports of its preparation yet. Based on the excipients of palbociclib capsules(Ibrance) from Pfizer, the formulation of generic palbociclib capsules was screened by orthogonal test, finally the optimal formulation was as follows: palbociclib 7.5 g, microcrystalline cellulose 11 g, lactose monohydrate 5.6 g, sodium carboxymethyl starch 1.59 g, colloidal silica 0.265 g, magnesium stearate 0.545 g for 100 capsules. During the preparation, 3% sodium carboxymethyl starch solution was used as adhesive for wet granulation, then the granules were dried at 60 ℃ and filled into the capsules. Meanwhile, a novel HPLC method for isolating and detecting five related substances of palbociclib was established. An Inert Sustain C_(18) column was used with ammonium acetate buffer(pH 5.7)∶acetonitrile as mobile phase by gradient elution. The detective wavelength was 225 nm. The method was validated with specificity, sensitivity, and durability. The results indicated that the novel HPLC method could be used for its related substances' analysis and quality control.
引文
[1]Baselga J,Campone M,Piccart M,et al.Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer[J].N Engl J Med,2012,366(6):520—529.
[2]Akinleye A,Avvaru P,Furqan M,et al.Phosphatidylinositol3-kinase(PI3K)inhibitors as cancer therapeutics[J].J Hematol Oncol,2013,6(1):88.
[3]Takalkar A,Adams S,Subbiah V.Radium-223 dichloride bone-targeted alpha particle therapy for hormone-refractory breast cancer metastatic to bone[J].Exp Hematol Oncol,2014,3(1):23.
[4]Verma S,Miles D,Gianni L,et al.Trastuzumab emtansine for HER2-positive advanced breast cancer[J].N Engl J Med,2012,367(19):1783—1791.
[5]Incorvati J A,Shah S,Mu Y,et al.Targeted therapy for HER2positive breast cancer[J].J Hematol Oncol,2013,6(23):38.
[6]王树森,佘鸿雁.Palbociclib联合来曲唑一线治疗ER阳性、HER2阴性进展期乳腺癌能显著提高无进展生存期[J].循证医学,2015,15(3):146—148.
[7]Zhang GP.Research progress of effects of palbociclib on advanced breast cancer[J].Chin Foreign Med Res,2016,14(11):151—152.
[8]Department of health and human services.Ibrance(palbociclib)capsules,for oral use FDA label[EB/OL].https://www.accessda ta.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf
[9]袁铎,朱雄,张仕金.Palbociclib有关物质的分析及合成[J].中国药科大学学报,2015,46(6):696—699.
[10]Ma XL,Liu L,Cao N,et al.Isolation and structural elucidation of palbociclib's eight process-related impurities:two identified as new compounds[J].J AOAC Int,2016,99(3):638—647.
[11]大卫·托马斯·埃尔德曼,卡斯林·马莉亚·弗拉弥.2-(吡啶-2-基氨基)-吡啶并[2,3-d]嘧啶-7-酮的合成:中国,101511829A[P].2009-08-19.
[12]Erdman D T,Flamme C M,Nelson J D.Synthesis of 2-(pyridin-2-ylamino)-pyrido[2,3-d]pyrimidin-7-ones:WO,2008032157[P].2008-03-20.
[13]Chekal BP,Ide ND.Solid forms of a selective CDK4/6inhibitor:WO,2014128588[P].2014-08-28.
[14]Carpino L A,Imazumi H,Foxman BX,et al.Comparison of the effects of 5-and 6-HOAt on model peptide coupling reactions relative to the cases for the 4-and 7-Isomers[J].Org Lett,2000,2(15):2253—2256.
[15]钟飞,鲍光明,党明珠.蒿甲醚胶囊的制备及其含量研究[J].海南师范大学学报:自然科学版,2012,25(4):402—406.
[16]陈琰,赵平,陈雯慧.芹菜籽胶囊的制备与质量研究[J].第二军医大学学报,2012,33(12):1347—1350.
[17]刘明,王慧森,李更生.正交试验优选强心胶囊制备工艺[J].中国实验方剂学杂志,2012,18(4):47—50.
[18]常艳,田冶,马越,等.呋布西林钠有关物质HPLC测定方法的建立[J].药学学报,2015,50(12):1632—1636.
[19]郑亚杰,张瑞萍,高杨,等.左氧氟沙星中杂质的LC-MS/MS定量分析方法及其市售制剂的质量评价研究[J].药学学报,2016,51(3):444—449.
[20]崇小萌,李进,王琰,等.阿莫西林克拉维酸钾片剂的关键质量属性与控制[J].药学学报,2016,51(7):1121—1124.
[21]何秀峰,王爱国,夏鹏飞,等.水杨酸甲酯乳糖苷片制剂工艺与质量研究[J].中国药学杂志,2013,48(10):797—800.
[22]姚静.药用辅料应用指南[M].北京:中国医药科技出版社,2011:53—85.
[2]Akinleye A,Avvaru P,Furqan M,et al.Phosphatidylinositol3-kinase(PI3K)inhibitors as cancer therapeutics[J].J Hematol Oncol,2013,6(1):88.
[3]Takalkar A,Adams S,Subbiah V.Radium-223 dichloride bone-targeted alpha particle therapy for hormone-refractory breast cancer metastatic to bone[J].Exp Hematol Oncol,2014,3(1):23.
[4]Verma S,Miles D,Gianni L,et al.Trastuzumab emtansine for HER2-positive advanced breast cancer[J].N Engl J Med,2012,367(19):1783—1791.
[5]Incorvati J A,Shah S,Mu Y,et al.Targeted therapy for HER2positive breast cancer[J].J Hematol Oncol,2013,6(23):38.
[6]王树森,佘鸿雁.Palbociclib联合来曲唑一线治疗ER阳性、HER2阴性进展期乳腺癌能显著提高无进展生存期[J].循证医学,2015,15(3):146—148.
[7]Zhang GP.Research progress of effects of palbociclib on advanced breast cancer[J].Chin Foreign Med Res,2016,14(11):151—152.
[8]Department of health and human services.Ibrance(palbociclib)capsules,for oral use FDA label[EB/OL].https://www.accessda ta.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf
[9]袁铎,朱雄,张仕金.Palbociclib有关物质的分析及合成[J].中国药科大学学报,2015,46(6):696—699.
[10]Ma XL,Liu L,Cao N,et al.Isolation and structural elucidation of palbociclib's eight process-related impurities:two identified as new compounds[J].J AOAC Int,2016,99(3):638—647.
[11]大卫·托马斯·埃尔德曼,卡斯林·马莉亚·弗拉弥.2-(吡啶-2-基氨基)-吡啶并[2,3-d]嘧啶-7-酮的合成:中国,101511829A[P].2009-08-19.
[12]Erdman D T,Flamme C M,Nelson J D.Synthesis of 2-(pyridin-2-ylamino)-pyrido[2,3-d]pyrimidin-7-ones:WO,2008032157[P].2008-03-20.
[13]Chekal BP,Ide ND.Solid forms of a selective CDK4/6inhibitor:WO,2014128588[P].2014-08-28.
[14]Carpino L A,Imazumi H,Foxman BX,et al.Comparison of the effects of 5-and 6-HOAt on model peptide coupling reactions relative to the cases for the 4-and 7-Isomers[J].Org Lett,2000,2(15):2253—2256.
[15]钟飞,鲍光明,党明珠.蒿甲醚胶囊的制备及其含量研究[J].海南师范大学学报:自然科学版,2012,25(4):402—406.
[16]陈琰,赵平,陈雯慧.芹菜籽胶囊的制备与质量研究[J].第二军医大学学报,2012,33(12):1347—1350.
[17]刘明,王慧森,李更生.正交试验优选强心胶囊制备工艺[J].中国实验方剂学杂志,2012,18(4):47—50.
[18]常艳,田冶,马越,等.呋布西林钠有关物质HPLC测定方法的建立[J].药学学报,2015,50(12):1632—1636.
[19]郑亚杰,张瑞萍,高杨,等.左氧氟沙星中杂质的LC-MS/MS定量分析方法及其市售制剂的质量评价研究[J].药学学报,2016,51(3):444—449.
[20]崇小萌,李进,王琰,等.阿莫西林克拉维酸钾片剂的关键质量属性与控制[J].药学学报,2016,51(7):1121—1124.
[21]何秀峰,王爱国,夏鹏飞,等.水杨酸甲酯乳糖苷片制剂工艺与质量研究[J].中国药学杂志,2013,48(10):797—800.
[22]姚静.药用辅料应用指南[M].北京:中国医药科技出版社,2011:53—85.