Development and validation of a sensitive liquid chromatography‐tandem mass spectrometry method for the assay of 12 substances in rat plasma and its application to rat pharmacokinetics of Epimedium and Psoraleae Fructus herb pair after oral administration

Epimedium (EM) and Psoraleae Fructus (PF) are a traditional herb combination often used as a fixed form to treat osteoporosis disease in the clinic. However, the intricate interactions of this pair remain unknown. In our study, we undertook a comprehensive examination of their compatibility behaviors. Concurrently, a precise and sensitive quantitation method was successfully developed and validated using liquid chromatography‐tandem mass spectrometry for the determination of 12 components. This method was applied in analyzing herbal extracts and biological samples (both in the portal vein and systemic plasma), which was also used to study the pharmacokinetics of the herb pair. The results indicated that the combination of EM and PF enhanced the dissolution of chemical components from PF in extracts, but it had a negligible influence on the contents of the components from EM. On the contrary, the in vivo exposure of the lowly exposed EM flavonoids significantly increased following the combination of EM and PF, whereas the highly exposed psoralen and isopsoralen were greatly reduced. These interactions might be crucial for the synergy and toxicity reduction of the herbal pair in disease treatment, which pave the way for further exploration into the clinical application and pharmacological mechanisms of EM and PF.