药物分子的相对疏水性及色谱保留行为研究

doi:10.7503/cjcu20170854

摘要/Abstract

摘要：

选取多种植物源药物作为模型药物, 基于不同药物的分子结构, 通过基团贡献法计算其溶度参数δ_t; 同时, 利用高效液相色谱(HPLC)测定模型药物的相对保留时间t_RR, 将δ_t与t_RR进行关联, 建立了经验模型t_RR=-0.032+7.27144$e^{-\delta_{t}/3.53874}$(相关系数R=0.97). 根据植物提取液中不同成分的分子结构计算其溶度参数, 基于该经验模型可推算其相对保留时间, 进而快速判断目标药物在疏水色谱分离过程中适宜的淋洗时间, 确定接收淋洗流动相的时间段.

关键词: 植物源药物, 溶度参数, 相对保留时间, 亲疏水性

Abstract:

Botanical medicine plays a significant role in research and production of new drugs, and attracts special attention due to its unique merits, such as rich source, less side effect. There exists certain difficulties to get target products from plant mixture in isolation and purification process. Reverse phase chromatography based on the difference in the polarity and hydrophobicity of drugs is one of the most important methods for purify active ingredients in plants. It is technical significant to establish a simple method to determine the hydrophobicity(retention time) of a target drug compound so as to design the stationary phase materials in chromatographic separation and collect mobile phase solution at an appropriate eluting period. In this study, a variety of botanical medicines were selected as model compounds, their solubility parameters δ_t were calculated by the group contribution method based on the molecular structure of the model compounds and relative retention times t_RR were determined by HPLC. The mathematical model correlating the solubility parameter and the relative retention time is established, t_RR=-0.032+7.27144$e^{-\delta_{t}/3.53874}$(R=0.97). By the method we established, the relative retention time of a drug compound can be obtained by calculating the solubility parameter, which can be used to predict the hydrophobicity and determine the appropriate elution time of such drug compound from hydrophobic membrane chromatography.

Key words: Botanical medicine, Solubility parameter, Relative retention time, Hydrophobicity

中图分类号:

O657

TrendMD:

杨桐, 彭荣, 黄新宇, 孙延松, 陈晓农. 药物分子的相对疏水性及色谱保留行为研究. 高等学校化学学报, 2018, 39(11): 2405.

YANG Tong, PENG Rong, HUANG Xinyu, SUN Yansong, CHEN Xiaonong. Relative Hydrophobicity of Drug Molecules and Retention Behavior in Hydrophobic Interaction Chromatography^†. Chem. J. Chinese Universities, 2018, 39(11): 2405.

图/表 5

参考文献 26

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Group	Number	F_di/(J^1/2·cm^3/2·mol^-1)	F_pi/(J^1/2·cm^3/2·mol^-1)	E_hi/(J·mol^-1)
—CH₃	1	205	0	0
—CH₂—	2	132	0	0
	8	39	0	0
	1	-34	0	0
CH₂=/—CH=	2	34	0	0
—COO—	1	191	239	1672
—OH(Alphatic series)	6	103	244	4777
—O—	3	49	196	717

Group	Number	F_di/(J^1/2·cm^3/2·mol^-1)	F_pi/(J^1/2·cm^3/2·mol^-1)	E_hi/(J·mol^-1)
—CH₃	1	205	0	0
—CH₂—	2	132	0	0
	8	39	0	0
	1	-34	0	0
CH₂=/—CH=	2	34	0	0
—COO—	1	191	239	1672
—OH(Alphatic series)	6	103	244	4777
—O—	3	49	196	717

Sample	t_R/min	t_RR	Sample	t_R/min	t_RR
Gastrodin	4.12	0	Aesculetin	11.16	0.1509
Gallic acid	5.04	0.0197	Paeoniflorin	12.58	0.1813
Danshensu	6.85	0.0585	Ecdysterone	13.43	0.1995
Aesculin	8.74	0.0990	Ferulic acid	15.54	0.2447
Protocatechuic acid	9.03	0.1052	Cinnamaldehyde	27.34	0.4976
Geniposide B	10.10	0.1282	Imperatorin	39.00	0.7475
Gentiopicrin	10.50	0.1367	Tanshinone IIA	50.78	1

Sample	t_R/min	t_RR	Sample	t_R/min	t_RR
Gastrodin	4.12	0	Aesculetin	11.16	0.1509
Gallic acid	5.04	0.0197	Paeoniflorin	12.58	0.1813
Danshensu	6.85	0.0585	Ecdysterone	13.43	0.1995
Aesculin	8.74	0.0990	Ferulic acid	15.54	0.2447
Protocatechuic acid	9.03	0.1052	Cinnamaldehyde	27.34	0.4976
Geniposide B	10.10	0.1282	Imperatorin	39.00	0.7475
Gentiopicrin	10.50	0.1367	Tanshinone IIA	50.78	1

Sample	t_RR	Solubility parameter/ (J·cm^-3)^1/2	Sample	t_RR	Solubility parameter/ (J·cm^-3)^1/2
Gastrodin	0	14.90	Aesculetin	0.1509	14.05
Gallic acid	0.0197	18.11	Paeoniflorin	0.1813	12.60
Danshensu	0.0585	16.00	Ecdysterone	0.1995	11.62
Aesculin	0.099	15.10	Ferulic acid	0.2447	10.59
Protocatechuic acid	0.1052	15.91	Cinnamaldehyde	0.4976	9.20
Geniposide B	0.1282	13.69	Imperatorin	0.7475	8.77
Gentiopicrin	0.1367	12.25	Tanshinone ⅡA	1	6.76