高效液相色谱法用于那格列奈质量控制的研究  

Study on the Quality Control of Nateglinide by HPLC

作　　者：张哲峰[1,2] 杨更亮[1,3] 周宇[1] 陈义[4] 

机构地区：[1]河北大学化学与环境学院河北省分析科学重点实验室 [2]河北省药品检验所 石家庄 050011 [3]中国科学院化学所分子科学中心 北京 100080 [4]中国科学院化学所分子科学中心

出　　处：《药物分析杂志》2004年第2期129-132,共4页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金资助项目(20075005);河北省自然科学基金资助项目(200077)

摘　　要：目的:建立那格列奈对映体、有关物质及含量测定的HPLC分析法。方法:采用OA-3300手性柱(250mm×4.6mm,5μm),柱温30℃,以0.025 mol·L-1醋酸铵的甲醇溶液为流动相,210 nm检测,分离对映体;LUNA ODS柱(250mm×4.6mm,5μm),乙腈-甲醇-0.1mol·L-1的磷酸二氢铵(5:2:4,用磷酸调pH 3.0)为流动相,210 nm检测,用于有关物质及含量测定。结果:D、L异构体分离度3.0以上,最低检出限分别为0.08和0.12 ng;顺反异构体及各中间体在20 min内较好分离,线性关系良好,最低检出限0.62 ng以下。结论:方法简便、快速、准确,两色谱系统结合,分别用于检测光学纯度、有关物质及含量,可在较高水平上控制本品质量。Objective:To establish HPLC methods for separating and determining the enantiomers,cis-and trans isomers, related substances and content of nateglinide. Methods: The chromatographic condition of the enantiomers separation:OA-3300(250 mm×4.6 mm,5 μm)column,a 0.025 mol ·L-1 ammonium acetate in methanol solution as mobile phase,the flow rate was 1.0 mL·min-1 ,the column temperature was at 30 ℃,the detection wavelength was 210 run. The chromatographic condition of the related substances and content determination: LUNA ODS (250mm×4. 6 mm,5μn)column,acetonitrile-methyl alcohol-0.1 mol·L-1(NH4)H2PO4(5:2:4)(adjusted to pH 3.0 with 85% phosphoric acid)as mobile phase,the flow rate and the detection wavelength was the same as above. Results:The two enantiomers could be separated within 12 minutes without derivatization and the resolution was above 3.0. The detection limits were 0.08 ng for D-and 0.12 ng for L-enantiomer,respectively. The five compounds, cis-and trans-isomers of nateglinide, cis-and trans-isomers of isopropylcyclohexylcarbic acid D phenylalanine could be separated within 20 minutes. The standard curves of the five compounds were good linear, and the detection limits came to below 0.62 ng. Conclusion:The developed methods have the advantages of simple, rapid and accurate, and could be used for quality control of the chiral purity, cis-isomer, related substances and content of nateglinide.

关 键 词：高效液相色谱法 那格列奈 质量控制 对映异构体 顺反异构体 手性分离 有关物质 

分 类 号：R977.15[医药卫生—药品] R927.11[医药卫生—药学]