SPE-HPLC法检测维生素D滴剂(软胶囊)中的有关物质  

Detection of related substances in vitamin D drops(soft capsules)by SPE-HPLC

作　　者：解植彩 杨丽娜 潘寒 徐庆君 卢大峰 李树英 谢强胜 XIE Zhi-cai;YANG Li-na;PAN Han;XU Qing-jun;LU Da-feng;LI Shu-ying;XIE Qiang-sheng(Enterprise's Technical Center of Qingdao Double Whale Pharmaceutical Co.,Ltd.,Qingdao 266109,China;Shandong Institute for Food and Drug Control,Jinan 250101,China)

机构地区：[1]青岛双鲸药业股份有限公司企业技术中心,青岛266109 [2]山东省食品药品检验研究院,济南250101

出　　处：《药物分析杂志》2024年第7期1238-1245,共8页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立固相萃取-高效液相色谱法(SPE-HPLC法)快速检测维生素D滴剂(软胶囊)中维生素D_(3)有关物质反式维生素D_(3)(杂质A)、7-去氢胆固醇(杂质B)、光甾醇3(杂质C)、异速甾醇3(杂质D)。方法:取内容物约1.2 g(约相当于维生素D_(3)1548 IU),精密称定,置于试管中,加入异辛烷4 mL,涡旋混匀,采用固相萃取小柱进行净化,以正己烷-乙酸乙酯(85∶15)为洗脱剂,无水乙醇为解吸剂;采用Luna Silica(2)100Å硅胶柱(150 mm×4.6 mm,3μm),以正己烷-正戊醇(996.5∶3.5)为流动相,采用加校正因子主成分自身对照法计算维生素D_(3)各杂质的含量。结果:前维生素D_(3)与植物油分离度>1.5。维生素D_(3)的线性范围为0.02~0.80μg·mL^(-1),r=0.9995;杂质A的线性范围为0.02~0.80μg·mL^(-1),r=0.9999;杂质B的线性范围为0.02~0.80μg·mL^(-1),r=0.9999;杂质C的线性范围为0.02~0.80μg·mL^(-1),r=0.9999;杂质D的线性范围为0.02~0.80μg·mL^(-1),r=0.9999。维生素D_(3)杂质A~D的平均回收率(n=9)为93.2%~102.9%。对3批维生素D滴剂(软胶囊)样品进行检测,结果已知杂质及其他最大单个杂质含量均≤0.5%,杂质总含量≤1.0%。结论:本方法经系统方法学验证,适用于维生素D滴剂(软胶囊)中维生素D_(3)有关物质的检测,且具有操作简便、快速、准确的优势,为脂溶性维生素D_(3)制剂的质量控制提供了技术保证。Objective:To establish a solid-phase extraction-high performance liquid chromatography(SPE-HPLC)method for the rapid detection of related substances of vitamin D_(3),trans vitamin D_(3)(impurity A),7-dehydrocholesterol(impurity B),lumisterol 3(impurity C),and isotachysterol 3(impurity D),in vitamin D drops(soft capsules).Methods:The content,which was approximately equivalent to vitamin D_(3)1548 IU,was taken in about 1.2 g,weighed accurately,put into a test tube,4 mL of isooctane was added to it,and it was swirled and mixed well.Purification was performed using solid phase extraction columns,with n-hexane-ethyl acetate(85∶15)as the elution agent and anhydrous ethanol as the desorption agent.A Luna Silica(2)100Åsilica gel column(150 mm×4.6 mm,3μm)was used,with n-hexane-n-pentanol(996.5∶3.5)as the mobile phase.The content of vitamin D_(3) impurities was calculated using the adding standard calibration factors principal component self-control method.Results:The separation degree between pre-vitamin D_(3) and vegetable oil was greater than 1.5.The linear range of vitamin D_(3) was 0.02-0.80μg·mL^(-1),with r=0.9995.The linear range of impurity A was 0.02-0.80μg·mL^(-1),with r=0.9999.The linear range of impurity B was 0.02-0.80μg·mL^(-1),with r=0.9999.The linear range of impurity C was 0.02-0.80μg·mL^(-1),with r=0.9999.The linear range of impurity D was 0.02-0.80μg·mL^(-1),with r=0.9999.The average recovery rate of impurities A-D(n=9)was 93.2%-102.9%.The detection results of 3 batches of vitamin D drops(soft capsules)showed that the content of known impurities and other maximum single impurities were less than 0.5%,and the total content of impurities was less than 1.0%.Conclusion:The results indicate that the established method is suitable for the detection of vitamin D_(3) related substances in vitamin D drops(soft capsules).It has the advantages of being easy to operate,providing rapid and accurate results,and providing technical assurance for the quality control of fat-soluble vitamin D_(3) preparat

关 键 词：固相萃取 高效液相色谱法 维生素D_(3)有关物质 工艺杂质 降解杂质 

分 类 号：R917[医药卫生—药物分析学]