Relative Hydrophobicity of Drug Molecules and Retention Behavior in Hydrophobic Interaction Chromatography†

doi:10.7503/cjcu20170854

Abstract

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

CLC Number:

O657

TrendMD:

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

Figures/Tables 5

References 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