Liu Kuangyi, Song Yonggui, Liu Yali, Peng Mi, Li Hanyun, Li Xueliang, Feng Bingwei, Xu Pengfei, Su Dan
Jiangxi University of Traditional Chinese Medicine, 56 Yangming Road, Nanchang 330006, PR China.
Jiangxi University of Traditional Chinese Medicine, 56 Yangming Road, Nanchang 330006, PR China.
J Pharm Biomed Anal. 2017 May 30;139:165-178. doi: 10.1016/j.jpba.2017.02.043. Epub 2017 Feb 27.
Currently the pharmacokinetic (PK) research of herbal medicines is still limited and facing critical technical challenges on quantitative analysis of multi-components from biological matrices which often accompanied by lacking of authentic standards and low concentration. This present work contributes to the development of an integrated strategy for extensive pharmacokinetics assessments, and a selective and sensitive method independent of authentic standards for multi-components analysis based on the use of ultra-performance liquid chromatography/quadrupole-time-of-flight/MS (UPLC-TOF-MS) and UPLC-TOF-MRM (rnhanced target). Initially, phytochemicals were identified by UPLC-TOF-MS analysis, subsequently the identified components were matched with authentic standards and pre-classified, and UPLC-QTOF-MRM method optimized and developed. To guarantee reliable results, three rules are necessary: (1) detection with a mass error of less than 5ppm; (2) same class chemical compositions with structural high similarity between analytes with and without authentic reference substance; (3) a matching retention time between TOF-MRM mode and TOF-MS within 0.2min. The developed and validated method was applied for the simultaneous determination of 12 lignans in rat plasma after administered with wine processed Schisandra Chinensis fructus (WPSCF) extract. Such an approach was found capable of providing extensive pharmacokinetic profiles of multi-components absorbed into blood after oral administrated with WPSCF extract. The results also indicated that significant difference in pharmacokinetics parameters of dibenzocyclooctadiene lignans was observed between schizandrin and gomisin compounds. For lignans, the absorption via gastrointestinal tract were all rapid and maintained relatively long retention time, especially for schisantherin A and schisantherin B with higher plasma exposure.
目前,草药的药代动力学(PK)研究仍然有限,并且在生物基质中多成分的定量分析上面临关键技术挑战,这通常伴随着缺乏标准品和低浓度的问题。本研究有助于开发一种用于广泛药代动力学评估的综合策略,以及一种基于超高效液相色谱/四极杆-飞行时间/质谱(UPLC-TOF-MS)和UPLC-TOF-MRM(增强靶向)的独立于标准品的多成分分析的选择性和灵敏方法。首先,通过UPLC-TOF-MS分析鉴定植物化学成分,随后将鉴定出的成分与标准品进行匹配并预分类,并优化和开发UPLC-QTOF-MRM方法。为了保证可靠的结果,需要三条规则:(1)质量误差小于5ppm的检测;(2)有和没有标准参考物质的分析物之间具有结构高度相似性的同类化学成分;(3)TOF-MRM模式和TOF-MS之间的保留时间匹配在0.2分钟内。所开发和验证的方法用于同时测定大鼠口服酒制五味子果实(WPSCF)提取物后血浆中的12种木脂素。发现这种方法能够提供口服WPSCF提取物后吸收到血液中的多成分的广泛药代动力学概况。结果还表明,五味子醇和戈米辛类化合物之间的二苯并环辛二烯木脂素药代动力学参数存在显著差异。对于木脂素,通过胃肠道的吸收都很快,并且保持相对较长的保留时间,特别是对于血浆暴露较高的华中五味子酯甲和华中五味子酯乙。