Background: Modern pharmacological studies show that rhizoma coptidis has protective effects on the liver, gallbladder, kidney, cerebral ischemia-reperfusion, local hypoxia injury, antiinflammatory, bone injury, nerve cells and myocardial cells. The effective components have been isolated from picroside I, II, III and IV.Introduction: A selective and sensitive ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed for the simultaneous quantitative determination of picroside I, II, III and IV in rat plasma to aid the pharmacokinetics studies. Methods: Sprague-Dawley (SD) rats were orally administered with 10 mg/kg, intravenously injected with 1 mg/kg for the mixture of picroside I, II, III and IV. The biological samples were collected at 0.083 3 h, 0.25 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h. A UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm) was used for chromatographic separation with the mobile phase consisting of acetonitrile and 0.1% formic acid by gradient elution. The flow rate was 0.4 mL/min. Multiple reaction monitoring (MRM) transitions were m/z 491.1→147.1 for picroside I, m/z 511.1→234.9 for picroside II, m/z 537.3→174.8 for picroside III and m/z 507.3→163.1 for picroside IV in negative ion mode. Results: The inter-day precision was less than 13%, the intra-day precision was less than 15%. The accuracy ranged from 89.4% to 111.1%. Recovery was higher than 79.1%, and the matrix effect ranged from 96.2% to 109.0%. Conclusion: The sensitive, rapid and selective UPLC-MS/MS method can be applied to the pharmacokinetic study of picroside I, II, III and IV in rats.
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