目的: 建立碳酸镧原料药固体样品中2个杂质的X-射线粉末衍射定量分析方法,用于碳酸镧原料药的稳定性研究和质量控制。方法: X-射线粉末衍射单峰法,通过检测参数优化提高检测灵敏度,以杂质Ⅰ的特征衍射峰2θ=17.8 °和杂质Ⅱ的特征衍射峰2θ=26.1 °的峰高为定量参数,建立峰高与杂质含量的线性关系,利用标准曲线法检测碳酸镧原料药样品中杂质Ⅰ和杂质Ⅱ的含量;通过优化混合方法,提高方法的重复性。结果: 杂质Ⅰ和杂质Ⅱ的特征衍射峰的峰高与其含量线性关系良好,杂质Ⅰ和杂质Ⅱ的检测限分别为0.55%和0.29%,杂质Ⅰ线性范围为0.55%~5.06%,线性方程Y=408.77X-103.8,r=0.992 1;杂质Ⅱ线性范围为0.29%~5.12%,线性方Y=816.95X-182.52,r=0.996 0;杂质Ⅰ和杂质Ⅱ的准确度分别为95.9%和96.1%,重复性的RSD分别为6.8%和7.1%。3批样品中杂质Ⅰ和杂质Ⅱ的含量均低于相应的检测限。结论: 本研究所建立的定量方法准确可靠,快速简便,可用于碳酸镧原料固体样品中2个杂质的定量分析。
Objective: To develop a method to determine the content of impurity Ⅰ and impurity Ⅱ in lanthanum carbonate raw materials by X-ray powder diffraction, and provide a simple, convenient and feasible quantitative analysis method for the stability research and quality control of lanthanum carbonate drugs. Methods: Single peak method, the detection sensitivity was improved by optimizing the detection parameters, and the characteristic diffraction peak of impurity I was 2θ=17.8 ° and characteristic diffraction peak of impurity Ⅱ was 2θ=26.1 °. The height of diffraction peak was used as the quantitative parameter, and the linear relationship between the peak height and impurity content was established. The content of impurity I and impurity Ⅱ in lanthanum carbonate API samples were determined by the standard curve method. By optimizing the hybrid method, the repeatability of the method was improved. Results: The heights of characteristic diffraction peaks of impurity Ⅰ and impurity Ⅱ showed a good linear relationship with their content. The detection limits of impurity Ⅰ and impurity Ⅱ were 0.55% and 0.29%, respectively. The linear range of impurity Ⅰ was 0.55%-5.06%, the linear equation was Y=408.77X-103.8, and the correlation coefficient r=0.992 1. The linear range of impurity Ⅱ was 0.29%-5.12%, the linear equation square was Y=816.95X-182.52, and the correlation coefficient r=0.996 0. The accuracy of impurity Ⅰ and impurity Ⅱ were 95.9% and 96.1% respectively, and the RSD of repeatability were 6.8% and 7.1% respectively. The contents of impurity Ⅰ and impuriyt Ⅱ in the three batches of samples were lower than the corresponding detection limit. Conclusion: The quantitative method established in this study is accurate, reliable, fast and simple, and can be used for the quantitative analysis of two impurities in lanthanum carbonate raw materials.
[1] JAN A, ANNE-LISE BM. Lanthanum carbonate-a new phosphate binding drug in advanced renal failure[J].Curr Med Chem, 2018, 25(1): 113
[2] HIROAKI O, MASAFUMI F, HIDEKI H, et al. Effect of treating hyperphosphatemia with lanthanum carbonate vs calcium carbonate on cardiovascular events in patients with chronic kidney disease undergoing hemodialysis: the LANDMARK randomized clinical trial[J].JAMA, 2021, 325(19): 1946
[3] 夏尔国际许可有限公司. 碱式碳酸镧的检定法: 中国, 200780024593.3[P].2009-07-15
Shire International Licensing Co., Ltd. Determination of Basic Lanthanum Carbonate: China, 200780024593.3[P].2009-07-15
[4] 张应. 碳酸镧的制备工艺研究及与碱式碳酸镧的鉴别研究[D].开封: 河南大学, 2012
ZHANG Y. Study on the Preparation of Lanthanum Carbonate and Identification of Basic Lanthanum Carbonate[D].Kaifeng: Henan University, 2012
[5] 马雨璇, 王娜, 李钢. 药用四水碳酸镧及其杂质碱式碳酸镧的定性和定量分析[J].分析仪器, 2021(4): 9
MA YX, WANG N, LI G. Qualitative and quantitative analysis of pharmaceutical lanthanum carbonate tetrahydrate and its impurity lanthanum basic carbonate[J].Anal Instrum, 2021(4): 9
[6] 梁敬魁. 粉末衍射法测定晶体结构: X射线衍射结构晶体学基础[M].北京: 科学出版社, 2011
LIANG JK. Determination of Crystal Structure by Powder Diffraction: Crystallographic Basis of X-ray Diffraction Structure[M].Beijing: Science Press, 2011
[7] 梁敬魁. 粉末衍射法测定晶体结构:X射线衍射在材料科学中的应用[M].北京: 科学出版社, 2011
LIANG JK. Determination of Crystal Structure by Powder Diffraction: application of X-ray diffraction in material science[M].Beijing: Science Press, 2011
[8] 肖燕, 王静康, 尹秋响, 等. 固体药物晶型定量分析方法[J].石油化工, 2015, 44(1): 8
XIAO Y, WANG JK, YIN QX, et al. Quantitative analyzing methods for polymorphism of pharmaceuticals[J].Petrochem Technol, 2015, 44(1): 8
[9] 戚淑叶, 邹文博, 姚尚辰, 等. 注射用头孢噻肟钠晶型一致性评价研究[J].药物分析杂志, 2021, 41(10): 8
QI SY, ZOU WB, YAO SC, et al. Evaluation of crystal form consistency of cefotaxime sodium for injection[J].Chin J Pharm Anal, 2021, 41(10): 8
[10] 中华人民共和国药典2020年版. 四部[S].2020: 55, 457
ChP 2020.Vol Ⅳ[S].2020: 55, 457
[11] ICH. Q2(R1): Validation of Analytical Procedures Text and Methodology[S].2005: 11
[12] 刘红超, 郭常霖. 研究固体微结构的X射线粉末衍射全谱图拟合方法[J].物理学进展, 1996, 16(2):23
LIU HC, GUO CL. X-Ray powder diffraction full-pattern-fitting method studying on the solid microstructure[J].Prog Phys, 1996, 16(2): 23
[13] 曾令民, 杨喜英, 王力珩, 等. X射线衍射里特沃尔德全谱图拟合法测定粉尘中游离的SiO2[J].分析化学, 2008, 36(5): 5
ZENG LM, YANG XY, WANG LH, et al. Determination of weight concentration of free silicon dioxide for dust using X-ray diffraction technique and rietveld refinement method[J].Chin J Anal Chem, 2008, 36(5): 5
[14] 徐婷, 王彦, 朱美兰, 等. 盐酸文拉法辛多晶型X-射线粉末衍射定量分析[J].中国新药杂志, 2017, 26(21): 6
XU T, WANG Y, ZHU ML, et al. Quantitative determination of venlafaxine hydrochloride polymorphs using X-ray powder diffractometry[J].Chin New Drugs J, 2017, 26(21): 6
[15] 黄继武, 李周. 多晶材料X射线衍射―实验原理、方法与应用[M].北京: 冶金工业出版社, 2012: 9
HUANG JW, LI Z. X-ray Diffraction of Polycrystalline Materials-Experimental Principle, Method and Application[M].Beijing: Metallurgical Industry Press, 2012: 9
