HPLC法测定替米沙坦中的有关物质  

Determination of related substances in telmisartan by HPLC

作　　者：王春 张素珍 陶鸿珠 彭亚 赵斌锋 WANG Chun;ZHANG Su-zhen;TAO Hong-zhu;PENG Ya;ZHAO Bin-feng(Zhejiang Kinglyuan Pharmaceutical Co.,Ltd.,Shaoxing 312369,China)

机构地区：[1]浙江金立源药业有限公司,绍兴312369

出　　处：《药物分析杂志》2024年第1期126-133,共8页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立高效液相色谱法测定替米沙坦原料药中的有关物质。方法:采用Waters Symmetry Shield RP8(150 mm×4.6 mm, 3.5μm)色谱柱,以0.1%磷酸溶液(用三乙胺调pH至3.0)-乙腈为流动相,梯度洗脱,流速0.8 mL·min^(-1),柱温25℃,检测波长230 nm。结果:替米沙坦与9种已知杂质色谱峰之间的分离度均>1.5,定量限均<40 ng·mL^(-1),检测限均<10 ng·mL^(-1)。替米沙坦及各杂质质量浓度在30~600 ng·mL^(-1)范围内线性关系良好(r>0.999 5)。杂质Ⅰ~杂质Ⅸ的平均回收率分别为93.8%、99.8%、97.5%、99.2%、99.8%、98.3%、98.4%、99.2%、99.7%,RSD均<2.0%。改变流速、柱温、波长、流动相比例及pH后,对有关物质的检测结果无影响。3批替米沙坦中最大单杂含量均为0.02%,杂质总量<0.10%。结论:经方法学验证,本方法专属性强,灵敏、精密,准确度高,可用于替米沙坦原料药有关物质的测定。Objective:To establish an HPLC method for the determination of the related substances in telmisartan. Methods: Waters Symmetry Shield RP8(150 mm×4.6 mm, 3.5 μm) column was adopted. The mobile phase A was 0.1% phosphoric acid solution(pH was adjusted to 3.0 with triethylamine), and the mobile phase B was acetonitrile. The gradient elution was performed. The flow rate, column temperature and wavelength were 0.8 mL·min^(-1), 25 ℃ and 230 nm, respectively. Results: The resolutions between the peaks of telmisartan and nine known impurities were greater than 1.5. The limits of quantitation of all impurities were less than 40 ng·mL^(-1), and the limits of detection of all impurities were less than 10 ng·mL^(-1). The standard curves of telmisartan and its impurities were linear within the range 30-600 ng·mL^(-1), and the correlation coefficients were all greater than 0.999 5. The average recovery rates of impurities Ⅰ-Ⅸ were 93.8%, 99.8%, 97.5%, 99.2%, 99.8%, 98.3%, 98.4%, 99.2% and 99.7%, respectively, and the RSDs of 9 results were all less than 2.0%. Changing the flow rate, column temperature, wavelength, mobile phase ratio and pH did not affect the detection results of the related substances. The results of maximum single impurity were 0.02% in three batches of telmisartan, and the results of total impurities were less than 0.10%. Conclusion: The method is highly specific, sensitive, precise and accurate, and can be used for the determination of related substances of telmisartan.

关 键 词：替米沙坦 原料药 有关物质 药典标准 质量控制 高效液相色谱法 梯度洗脱 

分 类 号：R917[医药卫生—药物分析学]