title: Qualitative and quantitative determination of complicated herbal components by liquid chromatography hybrid ion trap time-of-flight mass spectrometry and a relative exposure approach to herbal pharmacokinetics independent of standards.
abstract: To date, the pharmacokinetic research of herbal medicines (HMs) is still in its infancy and is facing critical technical challenges on the qualitative and quantitative analysis of complicated components from biological matrices. Additionally, the lack of authentic standards constitutes another bottleneck on assessing herbal pharmacokinetics. This present work contributes to the development of a powerful technical platform for both qualitative and quantitative pharmacokinetic analysis of herbal components, and a strategy of relative exposure that provides a practicable pharmacokinetic assessment independent of authentic standards, based on the use of liquid chromatography hybrid ion trap time-of-flight mass spectrometry (LC-IT-TOF/MS). Taking schisandra lignans extract (SLE) as an example, the LC-IT-TOF/MS assay was initially applied to the global qualitative analysis of components contained in SLE per se and in the rat plasma post SLE dosing. Afterwards, this study focused on validating the quantitative performance of LC-IT-TOF/MS assay by comparison with a well-established LC-Q/MS assay. For the absolute quantification of five lignans components with authentic standards, both assays showed very similar analytical figures of merit such as linearity, precision, accuracy, and pharmacokinetic parameters. Compared with LC-Q/MS, the prominent advantage of LC-IT-TOF/MS assay is its much higher sensitivity. Moreover, a 'relative exposure approach' (REA) that entails the use of sequentially diluted original herbal preparations to prepare the 'mixed calibration curves' was developed to assessing herbal pharmacokinetics independent of specific authentic compounds for each component. Such an approach was found capable of providing virtually identical pharmacokinetic parameters as that from the typical pharmacokinetic assay calibrated by authentic standards, except for the absolute plasma concentrations. The presently developed methodology and approach will find its wide use in, but not limited to, the qualitative and quantitative pharmacokinetic analysis of herbal medicines.
authors.affiliation: Key Lab of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, No. 24, Tongjiaxiang Street, Nanjing 210009, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Haiping
authors.initials: H
authors.lastname: Hao
authors.forename: An
authors.initials: A
authors.lastname: Kang
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Tong
authors.initials: T
authors.lastname: Xie
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng
authors.forename: Chen
authors.initials: C
authors.lastname: Dai
authors.forename: Leren
authors.initials: L
authors.lastname: Wan
authors.forename: Longsheng
authors.initials: L
authors.lastname: Sheng
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D013058:Mass Spectrometry / Q000379:methods*; D010936:Plant Extracts / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D032141:Schisandra / Q000737:chemistry*
chemical_list: D010936:Plant Extracts