Objective: To establish an LC-MS method for determination cannabidiol(CBD) in rat to verify the methodology and to study the influence of CBD on pharmacokinetics in normal rats. Methods: CBD solution(20, 50, 100 mg·kg-1) and CBD oil(50 mg·kg-1) were administrated intragastricly. The blood samples were collected before administration and at 0.083, 0.25, 0.5, 1,1.5,2,3, 4,5, 6, 7, 8, 10, 12, 24 and 48 h after administration. The concentrations of CBD were determined by LC-MS method, which using Waters Atlantis T3 column, 0.1% formic acid-water as mobile phase A, 0.1% formic acid-acetonitrile as mobile phase B, gradient elution, multiple reaction monitoring (MRM) andpositive ion mode detection. Winnonlin software package was used to analyze the calculations of pharmacokinetic parameters. Results: Excellent linear relationships of CBD were obtained in the serum. The recoveries of the analytes were 103.3%-115.7%. The intra-day RSDs of low, medium and high CBD concentrations were 3.3%, 1.5% and 0.29%, and the intra-day RSDs were 3.8%, 2.7%, and 5.8%,respectively. The extraction recoveries were (104.9±2.4)%, (115.7±0.4)% and (103.3±3.6)%. The sample was stable at -80 ℃. The Tmax of CBD solution was 2 h, and the Tmax of CBD oil was 9 h. The plasma concentrations of CBD in different doses were significantly different. Cmax and AUC increased with the dose, and MRT was between 7 and 13 h. Conclusion: The proposed method consumed shorter analysis time and less injection than investigation reported before. The specificity and sensitivity can meet requirements of serum pharmacokinetic assay. The CBD solution distributes rapidly in the blood, with a Tmax of only 2 h. The CBD solution and CBD oil quickly pass through the blood-brain barrier and enter the brain within 30 min after administration. The blood concentration of CBD administered with different doses is quite different, and Cmax and AUC increase with the dose.
AN Na, NIE Ying-lan
. Determination of cannabidiol in rat serum and its pharmacokinetic effects based on LC-MS/MS*[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(4)
: 630
-636
.
DOI: 10.16155/j.0254-1793.2022.04.09
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