中药多成分药代动力学分析技术研究进展

中药多成分药代动力学是中医药理论和作用机制阐明的重要研究内容。如何全面、准确地描述中药复杂成分在体内的药代动力学过程，诠释中药多成分、多靶标、多途径的特点，需要强有力的分析技术支撑。近年来，多种高通量、快速、自动化的前处理技术显著提升了中药体内外多成分的分离提取效率；色谱、质谱分析技术蓬勃发展，推动了中药体内外多成分的快速鉴别和全面、准确定量；质谱成像等新兴技术不断涌现，为中药多成分药代动力学研究提供了新的分析平台和研究手段。本文综述了近10年来中药多成分药代动力学研究分析技术的进展和应用，并对其前景进行展望。

Research Advance on Multi-Component Pharmacokinetic Analytical Techniques of Traditional Chinese Medicine

The multi-component pharmacokinetic of traditional Chinese medicine (TCM) is vital to clarify the theory and mechanism of TCM. Based on information of absorption, distribution, metabolism, and excretion dynamic changes for active components of TCM in vivo, the material basis for the safety and efficacy can be elucidated via combination with pharmacodynamics. However, due to the complexity and diversity of TCM components, and their complicated and unclear interactions with biological system, there are many bottleneck problems for the multi-component pharmacokinetics of TCM, such as the numerous chemical composition and diverse metabolic reaction make it difficult to identify their structures and interpret metabolic pathway in vivo; and unclear active components, low concentrations of target components in biological samples, endogenous interferences from matrix and lack of authentic standards bring difficulties to establish qualitative and quantitative methods. In recent years, the pretreatment methods for biological samples have been well developed. The separation and extraction efficiency for multi-component of TCM in vivo and in vitro have been significantly improved using various high-throughput, fast and automated pretreatment techniques. The development of chromatography and mass spectrometry promotes the rapid comprehensive and accurate discovery and quantification for multi-component of TCM. Novel analytical methods such as mass spectrometry imaging were used to provide new strategies for multi-component pharmacokinetics of TCM. In this paper, the development and application of analytical techniques for multi-component pharmacokinetic of TCM in the past 10 years were summarized, and a brief perspective was discussed. Firstly, the pretreatment of biological sample was introduced, the advantages and disadvantages of some usual sample pretreatment methods were compared such as protein precipitation and liquid-liquid extraction, solid phase extraction, microextraction, microdialysis. The applications of these different pretreatment techniques in the pharmacokinetics research of TCM were interviewed. Then, the principles and developments of different chromatographic techniques including high performance liquid chromatography and gas chromatography used in multi-component pharmacokinetic of TCM were introduced. Finally, the mass spectrometry ionization techniques were summarized and discussed including electrospray ionization and atmospheric pressure chemical ionization for liquid chromatography, electron impact and chemical ionization for gas chromatography, desorption electrospray ionization, direct analysis in real time, mass spectrometry imaging.