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<p>Tissue pharmacokinetics is crucial for druggability assessment and plays a vital role in identifying the core bioactive components of traditional Chinese medicines (TCMs). This study aims to develop an integrated analytical approach combining ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to systematically characterize the temporal and spatial brain exposure profiles of <i>Corydalis Decumbentis Rhizoma</i> (CDR) in rats. Using UPLC-quadrupole time of flight mass spectrometry (UPLC-QTOF), a total of 35 drug-derived constituents were identified from rat brain after oral administration of CDR. Then, a rapid and sensitive UPLC-triple-stage quadrupole mass spectrometry (UPLC-TSQ) method was developed and validated for the quantification of 15 major alkaloids in rat brain tissue. The pharmacokinetic results indicated that most compounds reached peak concentrations within 4 h and were rapidly eliminated within 12 h. Tetrahydropalmatine and protopine exhibited notably high brain exposure levels (AUC<sub>0-t</sub> &gt; 100 ng·h·g⁻<sup>1</sup>), suggesting their potential as key active constituents responsible for the anti-ischemic effects of CDR. DESI-MSI further revealed the spatial distribution of these compounds, with most alkaloids predominantly localized in the telencephalon. The spatial distribution of CDR constituents furnished a scientific basis for its traditional application against cerebral ischemic injury. This study provides a scientific basis for the anti-stroke effects of CDR and a reference for investigating the material basis of other TCMs.</p> Graphical abstract <p></p>

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Elucidating spatiotemporal distribution of chemical constituents from Corydalis Decumbentis Rhizoma in rat brain via integrated UPLC-MS/MS quantification and DESI-MSI visualization

  • 期刊论文

  • 发表日期：

    2025年11月12日

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  • Xiaoshuang Li,
  • Sijian Chen,
  • Wenxin Zhang,
  • Yuqi Wang,
  • Peng Gao,
  • Yulin Ouyang,
  • Chun Li,
  • Yingyuan Lu,
  • Pengfei Tu

摘要

Tissue pharmacokinetics is crucial for druggability assessment and plays a vital role in identifying the core bioactive components of traditional Chinese medicines (TCMs). This study aims to develop an integrated analytical approach combining ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to systematically characterize the temporal and spatial brain exposure profiles of Corydalis Decumbentis Rhizoma (CDR) in rats. Using UPLC-quadrupole time of flight mass spectrometry (UPLC-QTOF), a total of 35 drug-derived constituents were identified from rat brain after oral administration of CDR. Then, a rapid and sensitive UPLC-triple-stage quadrupole mass spectrometry (UPLC-TSQ) method was developed and validated for the quantification of 15 major alkaloids in rat brain tissue. The pharmacokinetic results indicated that most compounds reached peak concentrations within 4 h and were rapidly eliminated within 12 h. Tetrahydropalmatine and protopine exhibited notably high brain exposure levels (AUC0-t > 100 ng·h·g⁻1), suggesting their potential as key active constituents responsible for the anti-ischemic effects of CDR. DESI-MSI further revealed the spatial distribution of these compounds, with most alkaloids predominantly localized in the telencephalon. The spatial distribution of CDR constituents furnished a scientific basis for its traditional application against cerebral ischemic injury. This study provides a scientific basis for the anti-stroke effects of CDR and a reference for investigating the material basis of other TCMs.

Graphical abstract