光动力治疗用福大赛因异构体的拆分及结构鉴定  

Structural identification and quality study on isomers of a novel anticancer photosensitiser Photocyanine

作　　者：杨蓓蓓[1] 么会生 刘宏[2] 江舟[2] 王建[2] 贺文义[1] 王琰[1] 陈耐生[2] 黄金陵[2] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050 [2]福州大学功能材料研究所,福建福州350002

出　　处：《药学学报》2010年第12期1545-1549,共5页Acta Pharmaceutica Sinica

基　　金：国家科技重大专项综合平台资助项目(2009ZX09301-003-7-1);福建省教育厅科技资助项目(JA09011;JA09016)

摘　　要：光动力治疗用抗癌光敏剂"福大赛因"是ZnPcS2P2中4个异构体组成的取代酞菁化合物的混合物,为了更好地对"福大赛因"进行质量研究和质量控制,需要对这4个结构相似、化学性质相近的同分异构体进行拆分及结构鉴定。本研究以反相C18色谱柱,乙腈-0.01 mol.L-1十六烷基三甲基溴化铵-0.01 mol.L-1 KH2PO4(用KOH试液调至pH 6.8)为流动相进行梯度洗脱(0 min 60%～30 min 65%),流速为1.0 mL.min-1,在674 nm波长处检测,4个同分异构体得到较好分离。采用反相C18半制备柱,通过反复进样首次成功分离、制备了4个同分异构体纯品,并进行了1H NMR谱、gCOSY、NOE1D谱测定。通过已知的酞菁母核结构特征,推断了4个异构体的结构。同时对FD-1、FD-2、FD-3、FD-4四个异构体通过HPLC/DAD含量测定方法学研究,4个异构体在测定范围内呈良好的线性关系,方法的精密度(以RSD%表示)分别为0.12%、0.66%、0.99%和1.21%,最低检出限分别为15、20、12和25 ng。实现了以单一成分来控制福大赛因的质量,并测定了10份不同批次的样品,为完善"福大赛因"的质量标准提供了依据。Our work focuses on the quality control and structural identification of Photocyanine as a cancer therapeutic photosensitizer.Photocyanine is a mixture which contains four ZnPcS2P2 type substituted Phthalocyanine isomers.In order to obtain the single component from Photocyanine,the mixture of four isomers possessing the similar structures and chemical property had been isolated and purified.An HPLC method with a mixture of methanol-acetonitrile-ion-pair buffer as the mobile phase was applied to isolate the four isomers by means of a semi-preparative C18 column.To remove the salts which were mixed in the preparative product,a SPE C18 column was used to separate the salts by elution with water and then the marker component was eluted by methanol.Subsequently,a column of Sephadex LH-20 gel was applied to elute the crudes with methanol to desalination.The purity of the isolated compound was measured by TLC and four different isomers of phthalocyanine were obtained.The chemical structures of them were elucidated by 1H NMR spectra,gCOSY and NOE1D.An HPLC-DAD method was developed for simultaneously determination of four major isomers in Photocyanine with a C18 column（Grace Smart,150 mm × 4.6 mm ID,5 μm）.The separation was carried out with a gradient program at a flow rate of 1.0 mL.min？1.The mobile phase was a mixture of acetonitrile and ion-pair buffer（0.01 mol.L？1 hexadecyl trimethyl ammonium bromide and 0.01 mol.L-1 potassium dihydrogen phosphate,adjusted the pH value to 6.8 with potassium hydroxide solution）.The resolution values of four isomers were 2.5,1.20,1.33,and 1.8.Linear regression analysis for four compounds was performed by the external standard method.Four constituents were linear in the concentration range of 0.005 to 10 μg.The values of relative standard deviation（RSD） of intra-day were 0.12%,0.66%,0.99%,and 1.21%,respectively.The limits of detection for four compounds were 15 ng,20 ng,12 ng,and 25 ng,respectively.This method was simple,accurate and reproducible.The developed method c

关 键 词：舒他兰锌 福大赛因 抗癌光敏剂 酞菁异构体 拆分分析 结构鉴定 

分 类 号：R917[医药卫生—药物分析学]