Simultaneous determination of caffeic acid derivatives by UPLC-MS/MS in rat plasma and its application in pharmacokinetic study after oral administration of Flos Lonicerae-Fructus Forsythiae herb combination

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• 作者：Wei Zhou ; Jinjun Shan ; Shouquan Wang ; Wenzheng Ju ; Minxin Meng ; Baochang Cai ; Liuqing Di
• 关键词：Flos Lonicerae&ndash ; Fructus Forsythiae herb combination ; Caffeic acid derivatives ; UPLC&ndash ; MS/MS ; Oral delivery ; Pharmacokinetics
• 刊名：Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences
• 出版年：15 February, 2014
• 年：2014
• 卷：949-950
• 期：Complete
• 页码：7-15
• 全文大小：2005 K

文摘

The current study aims to investigate the pharmacokinetic study of eight caffeic acid derivatives (forsythoside A, isoforsythoside, forsythoside B, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 3,5-dicaffeoylquinic acid and 3,4-dicaffeoylquinic acid) following oral administration of Flos Lonicerae-Fructus Forsythiae herb combination in rats. A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to determine the eight caffeic acid derivatives simultaneously in rat plasma. After mixing with the internal standard (IS) tinidazole, plasma samples were pretreated by liquid-liquid extraction with n-butyl alcohol/ethyl acetate (7:3, v/v). The separation was performed on an Acquity UPLC HSS T3 C18 column (100 mm 脳 2.1 mm, 1.8 渭m) at a flow rate of 0.4 mL min^鈭?, and acetonitrile/methanol (4:1, v/v)-0.4% formic acid was used as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with positive and negative ionization modes. All calibration curves had good linearity (r > 0.991) over the concentration ranges of 1.097-2246 ng mL^鈭? for neochlorogenic acid, 6.535-6692 ng mL^鈭? for chlorogenic acid, 2.103-2153 ng mL^鈭? for cryptochlorogenic acid, 0.5058-129.5 ng mL^鈭? for 3,5-dicaffeoylquinic acid, 0.3205-82.05 ng mL^鈭? for 3,4-dicaffeoylquinic acid, 1.002-512.8 ng mL^鈭? for isoforsythoside, 0.4795-982.1 ng mL^鈭? for forsythoside A and 0.7587-776.9 ng mL^鈭? for forsythoside B, respectively. The intra- and inter-batch precisions were all within 15% and the accuracy (relative error, RE%) all ranged from 85.68% to 114.7%. It was shown from pharmacokinetic parameters that the rank order of AUC_0-t, C_max and T_1/2k for phenolic acids was chlorogenic acid > neochlorogenic acid 鈮?#xA0;cryptochlorogenic acid > 3,4-dicaffeoylquinic acid 鈮?#xA0;3,5-dicaffeoylquinic acid (most of them had significant differences), which corresponded to their administration dosages to rats, but that of MRT_0-t and T_1/2z were opposite. Besides, the AUC_0-t, C_max, MRT and T_1/2z except T_1/2k of isoforsythoside and forsythoside B had no significant difference, compared to that of forsythoside A though their administration dosages were significantly lower than that of forsythoside A. All results showed that the method was applied to the pharmacokinetic study of the eight caffeic acid derivatives in rat plasma successfully after oral administration of Flos Lonicerae-Fructus Forsythiae herb combination, and there were significant differences of caffeic acid derivatives even isomers in the pharmacokinetic parameters.