吕湘林, 汪秀云, 曹秀玲. dl-15-甲基PGF2α及其甲酯的HPLC分析研究J. 药学学报, 1987, 22(12): 901-907.
引用本文: 吕湘林, 汪秀云, 曹秀玲. dl-15-甲基PGF2α及其甲酯的HPLC分析研究J. 药学学报, 1987, 22(12): 901-907.
LU Xiang-Lin, WANG Xiu-Yun , CAO Xiu-Ling, . SEPARATON AND DETERMINATION OF dl-15-METHYL PGF2α AND ITS METHYL ESTER BY HPLCJ. Acta Pharmaceutica Sinica, 1987, 22(12): 901-907.
Citation: LU Xiang-Lin, WANG Xiu-Yun , CAO Xiu-Ling, . SEPARATON AND DETERMINATION OF dl-15-METHYL PGF2α AND ITS METHYL ESTER BY HPLCJ. Acta Pharmaceutica Sinica, 1987, 22(12): 901-907.

dl-15-甲基PGF2α及其甲酯的HPLC分析研究

SEPARATON AND DETERMINATION OF dl-15-METHYL PGF2α AND ITS METHYL ESTER BY HPLC

  • 摘要: dl-15-甲基PGF2α及其甲酯为前列腺素PGF的衍生物。它们的临床剂量甚小,其合成生产工艺及结构特征表明可能有多种异构体存在,且异构体间的生物活性差异很大。建立具有高专属性、灵敏度以及对各种制剂适用的分析方法是改进生产工艺、深入各项研究和临床安全有效使用所面临的迫切课题。本文报道的反相HPLC直接测定法用ODS柱、UVλ197nm检测、甲醇—水—醋酸为流动相,合成杜鹃素为内标,可对dl-15-甲基PGF2α及其甲酯的各种差向和顺反异构体进行分离和分别直接定量。本法分辨率高,最低检测量为0.03μg,操作简便,定量线性关系良好,分析误差小于3%(CV),节省试剂,并可发展成制备工艺。本法适用于15-甲基PGF2α及其甲酯的合成原料和各种制剂的分析。

     

    Abstract: The dl-15-methyl PGF2α and its methyl ester are the derivatives of PGF. They are used clinically in very low dose and show great difference in biological activities with different configurations.There are two epimer pairs of the 15-methyl (R & S), and C-5,6 (cis & trans).After careful study of the chromatographic behaviours and configuration relationships between these epimers in various chemically bonded phases, which are amino-, cyano-, phenyl-, fluoroether-, C8-, and ODS, and compare the different components of the mobile phase, a reverse phase methed using ODS column and methanol-water-acetic acid (130:100:0.125)as mobile phase is proposed.This study also revealed that the UV max of PGF at shorter wavelength (max 195~197nm) can still be detected with enough sensitivity. The minimum detectable quantity is 0.03 μg with credibility.A procedure of directly introducing the sample solution with internal standard (farrerol) into the chromatographic system and detecting by UV 195~197 nm was suggested. A good resolution between epimer R and S (Rs>3), cis-and trans-isomer (Rs>1.5) can be obtained.The method exhibits very high accuracy (CV<3%) and can be used in a variety of their preparations, e.g. injections, suppositories and sponges (recovery>99%).Several epimer impurities had been separated by the established method in a number of "pure reference standard" of the Upjohn Company.The analytical results showed that the white crystaline products from the Shanghai Institute of Organic Chemistry was very pure in which epimer was not detected.

     

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