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

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2014-02, Vol.949-950, p.7-15
• Main Authors: Zhou, Wei, Shan, Jinjun, Wang, Shouquan, Ju, Wenzheng, Meng, Minxin, Cai, Baochang, Di, Liuqing
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Caffeic acid derivatives; Caffeic Acids - blood; Caffeic Acids - chemistry; Chlorogenic acid; Chromatography; Chromatography, High Pressure Liquid - methods; Derivatives; Dosage; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacokinetics; Flos Lonicerae–Fructus Forsythiae herb combination; Herbs; Ionization; Linear Models; Male; Methyl alcohol; Oral delivery; Pharmacokinetics; Plant Extracts - administration & dosage; Plant Extracts - pharmacokinetics; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry - methods; UPLC–MS/MS
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2013.12.035

•Simultaneous analysis of caffeic acid derivatives in vivo was studied firstly.•The pharmacokinetic study of isoforsythoside was reported firstly.•The pharmacokinetic study of forsythoside B was also reported firstly.•The method was fully validated and applied to the pharmacokinetic study.•There were significant differences of isomers in the pharmacokinetic parameters. 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 (100mm×2.1mm, 1.8μm) at a flow rate of 0.4mLmin−1, 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 1.097–2246ngmL−1 for neochlorogenic acid, 6.535–6692ngmL−1 for chlorogenic acid, 2.103–2153ngmL−1 for cryptochlorogenic acid, 0.5058–129.5ngmL−1 for 3,5-dicaffeoylquinic acid, 0.3205–82.05ngmL−1 for 3,4-dicaffeoylquinic acid, 1.002–512.8ngmL−1 for isoforsythoside, 0.4795–982.1ngmL−1 for forsythoside A and 0.7587–776.9ngmL−1 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 AUC0–t, Cmax and T1/2k for phenolic acids was chlorogenic acid>neochlorogenic acid≥cryptochlorogenic acid>3,4-dicaffeoylquinic acid≥3,5-dicaffeoylquinic acid (most of them had significant differences), which corresponded to their administration dosages to rats, but that of MRT0–t and T1/2z were opposite. Besides, the AUC0–t, Cmax, MRT and T1/2z except T1/2k of i