Ultra‐High Performance Liquid Chromatography/Triple Quadrupole Ion‐Trap Mass Spectrometry‐Based Quantitative Assay of 17 Compounds to Unveil the Extraction Difference of Potentially Toxic Components Between the Single Drugs and Sishen Formula

ABSTRACT Sishen formula is a famous prescription utilized to treat kidney diarrhea. The main components of Psoraleae Fructus and Euodiae Fructus are reported with the liver toxicity; however, the dissolution difference of those reported toxic compounds among the single medicine decoctions and those versatile compatibility forms has yet not been documented by quantitative assays. We established and validated an ultra‐high performance liquid chromatography/triple quadrupole‐linear ion‐trap mass spectrometry‐multiple reaction monitoring approach by targeting 17 components (e.g., four coumarins and eight flavonoids from Psoraleae Fructus; three alkaloids and two limonoids from Euodiae Fructus). Co‐decoction with Myristicae Semen or Schisandrae Chinensis Fructus could significantly affect the dissolution of coumarins and flavonoids from Psoraleae Fructus, whereas a weak influence was observed for combining Euodiae Fructus with Psoraleae Fructus. Combination with Schisandrae Chinensis Fructus could significantly increase the contents of both alkaloids and limonoids of Euodiae Fructus, but the effect of Myristicae Semen or Psoraleae Fructus was relatively slight. Moreover, the dissolution of Psoraleae Fructus coumarins and Euodiae Fructus limonoids in Sishen formula was remarkably inhibited, compared with the pure Psoraleae Fructus decoction, whereas the variation was weak between the Euodiae Fructus decoction and Sishen formula. These results benefit the bridge to the efficacy and toxicity changes of Sishen formula.