Pharmacokinetics and Tissue Distribution of Four Characteristic Constituents from Cocculus orbiculatus in Rats Using UHPLC-Q-trap-MS/MS

Abstract Background Cocculus orbiculatus (L.) DC, a plant belonging to the genus Cocculus of the Menispermaceae, is rich in alkaloids, flavonoids, and other constituents, and exhibits anti-inflammatory and antimicrobial activities. However, studies on the in vivo processes of its bioactive components remain limited. Objective This study established a UHPLC-Q-trap-MS/MS-based detection method to explore the pharmacokinetic profile and tissue distribution of magnoflorine, oblongine, syringic acid, and laurifoline in rats after intragastric administration of Cocculus orbiculatus extract. Method A UHPLC-Q-trap-MS/MS method with MRM in ESI± modes was developed to quantify magnoflorine, laurotetanine, oblongine, and syringic acid in rat plasma and tissues (heart, liver, spleen, lung, kidney, prostate, intestine, and stomach) after oral administration of Cocculus orbiculatus extract to SD rats. Results No obvious interference from endogenous substances was observed for the internal standard and analytes in plasma and liver samples, and the established method exhibited good linearity, with correlation coefficients r exceeding 0.999. In addition, the precision, accuracy, stability, matrix effect, and extraction recovery of this method met the requirements of biological sample analysis. Pharmacokinetic results indicated that after intragastric administration, magnoflorine, oblongine, and syringic acid were eliminated rapidly, while laurifoline was eliminated slowly. Tissue distribution results revealed that magnoflorine, oblongine, and laurifoline were detectable in all examined tissues, with the highest levels in the intestine and stomach, while syringic acid was detectable only in the kidney and stomach. Conclusions In this study, the established method enables sensitive detection of chemical components in plasma and tissues, exhibiting good selectivity, specificity, precision, and reproducibility. Therefore, the obtained pharmacokinetic parameters and tissue distribution characteristics can provide references for optimizing clinical dosing regimens and exploring pharmacodynamic mechanisms. Highlights Results from this study offer important insights into administration dosage in pharmacodynamic research of Cocculus orbiculatus and support further exploration of its pharmacodynamic material basis.