LC-MS/MS-Based Concurrent Quantification of Cannabidiol and Melatonin in Mouse Plasma to Elucidate Complex PK...

Area of Science:

• Pharmacology and Toxicology
• Analytical Chemistry

Background:

• Cannabidiol (CBD) and melatonin (MT) are compounds with significant physiological effects.
• Understanding their pharmacokinetic interactions is crucial for therapeutic applications and safety assessments.

Purpose of the Study:

• To develop and validate a quantitative LC-MS/MS method for simultaneous determination of CBD and MT in mouse plasma.
• To investigate the pharmacokinetic interactions between CBD and MT in vivo.

Main Methods:

• A protein precipitation method was employed for sample preparation.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for analysis.
• Pharmacokinetic parameters were determined in male ICR mice following intravenous and oral administrations of MT and CBD.

Main Results:

• A robust LC-MS/MS method was established for quantifying CBD and MT in mouse plasma.
• Oral co-administration of high-dose CBD (40 mg/kg) significantly altered MT (10 mg/kg) pharmacokinetics, affecting Cmax and AUC.
• Intravenous CBD also influenced MT's oral bioavailability, indicating complex interactions.

Conclusions:

• The developed LC-MS/MS method is suitable for pharmacokinetic studies of CBD and MT.
• CBD exhibits complex effects on MT pharmacokinetics, potentially inhibiting intestinal absorption and metabolic clearance at high oral doses.
• These findings highlight the need for careful consideration of CBD-MT co-administration in preclinical and clinical settings.