Quantification of thonningianin a in rat plasma by liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study

CONTEXT: Thonningianin A is an ellagitannin substance and displays multiple pharmacological activities. OBJECTIVE: This study investigated the pharmacokinetic characteristics of thonningianin A after oral administration in rats using a fully validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. MATERIALS AND METHODS: A sensitive and selective LC-MS/MS assay was developed for quantifying thonningianin A. Eighteen Wistar rats were randomly divided into three groups (n = 6), which were given at a single dose of 10, 20, or 40 mg/kg thonningianin A by gavage. Blood samples (200 µL) were collected from the orbit vein at designated time points and analyzed using the LC-MS/MS method to measure the levels of thonningianin A. RESULTS: Thonningianin A and internal standard (IS) were eluted at 1.5 and ∼3.0 min, respectively. The selected reaction mode transitions monitored were m/z 873.2 > 300.3 and 819.3 > 610.6 for thonningianin A and the IS, respectively. The calibration range was 10–1200 ng/mL. The intra- and the inter-day accuracy and precision met the acceptance criteria. No carryover and matrix effect were observed. The plasma concentrations of thonningianin A increased rapidly after oral administration of three dosages and reached the mean peak concentrations (C(max)) within 0.61–0.83 h. Meanwhile, AUC(0–t)/AUC(0–∞) of the three dosage groups was more than 89.0% (10 mg/kg), 95.7% (20 mg/kg), and 97.0% (40 mg/kg). DISCUSSION AND CONCLUSIONS: The present method is the first report in terms of the simple precipitation procedure, high sensitivity, and high-throughput efficiency. This validated assay was successfully applied to determine the pharmacokinetic behaviours of thonningianin A in rats. This study should be helpful for providing references for understanding the action mechanism and further application of Penthorum chinense.