论文部分内容阅读
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。
Photodynamic therapy with anti-cancer photosensitizer “Fu major race because of ” is ZnPcS2P2 four isomers in the composition of the mixture of substituted phthalocyanine compounds, in order to better the “Fortes 赛 因” for quality research and quality control , The four structurally similar, chemically similar isomers need to be resolved and their structures identified. In this study, reversed-phase C18 column, acetonitrile-0.01 mol.L-1 cetyltrimethylammonium bromide-0.01 mol.L-1 KH2PO4 (adjusted to pH 6.8 with KOH solution) as the mobile phase gradient (0 min 60% ~ 30 min 65%) at a flow rate of 1.0 mL.min-1, detected at a wavelength of 674 nm, and the four isomers were well separated. Four reversed-phase C18 semi-preparative columns were successfully separated by repeated injections. Four isomers were prepared and analyzed by 1H NMR, GCOSY and NOE1D spectra. The structure of four isomers was deduced from the known structural characteristics of the phthalocyanine core. At the same time, four isomers of FD-1, FD-2, FD-3 and FD-4 were studied by HPLC / DAD method. The four isomers showed a good linear relationship in the determination range. Degrees (in RSD%) were 0.12%, 0.66%, 0.99% and 1.21%, respectively, and the lowest detection limits were 15, 20, 12 and 25 ng, respectively. It realizes the control of the quality of Forsythin by a single component and determines the samples of 10 different batches, which provides the basis for the improvement of the quality standard of Forsythe.