Wang Mengran, Zhang Wenpeng, Wu Xia, Wang Lingchao, Li Cong, Liu Chunyan, Zhuang Xiaomei
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
College of Pharmacy, North China University of Science and Technology, Tangshan 063210, China.
Pharmaceutics. 2024 Nov 25;16(12):1511. doi: 10.3390/pharmaceutics16121511.
This study aimed to develop a quantitative analytical method for the simultaneous determination of cannabidiol (CBD) and melatonin (MT) in mouse plasma using the protein precipitation method coupled with LC-MS/MS. Additionally, this study sought to investigate the impact of CBD on the pharmacokinetics of MT in mice using this method. Mouse plasma samples were precipitated with acetonitrile and analyzed using a Kromasil 100-5-C8 (2.1 × 50 mm) column. Following a single administration, thirty male ICR mice were randomly assigned to five groups: MT 2 mg/kg intravenously (), MT 10 mg/kg orally (), MT + CBD (10 + 10) mg/kg , MT + CBD (10 + 40) mg/kg , and MT 10 mg/kg followed by CBD 2 mg/kg Pharmacokinetic parameters were calculated using a non-compartmental model and analyzed to investigate the interactions of CBD with MT. The calibration curves for CBD and MT were linear over the range of 2 to 1000 ng/mL. Co-administration of a high dose of CBD (40 mg/kg) orally reduced the C of MT (10 mg/kg) to 57% of the control, while the area under the curve from 0.5 to 8 h (AUC) was 2.85-fold that of the MT-only group. When CBD (2 mg/kg) was administered intravenously alongside MT orally, the AUC was 1.54 times that of MT given orally alone. The AUC of CBD was positively correlated with the AUC of the distribution and elimination phases of MT, while the C of CBD negatively correlated with the C of MT. The developed LC-MS/MS method is robust and suitable for pharmacokinetic studies involving CBD and MT. The in vivo effects of CBD on MT pharmacokinetics are complex. High oral doses of CBD inhibit both the intestinal absorption and metabolic clearance of MT, resulting in a more smooth PK profile.
本研究旨在开发一种采用蛋白沉淀法结合液相色谱 - 串联质谱（LC - MS/MS）同时测定小鼠血浆中大麻二酚（CBD）和褪黑素（MT）的定量分析方法。此外，本研究试图使用该方法研究CBD对小鼠体内MT药代动力学的影响。小鼠血浆样品用乙腈沉淀，并用Kromasil 100 - 5 - C8（2.1×50 mm）色谱柱进行分析。单次给药后，将30只雄性ICR小鼠随机分为五组：静脉注射MT 2 mg/kg（）、口服MT 10 mg/kg（）、MT + CBD（10 + 10）mg/kg 、MT + CBD（10 + 40）mg/kg 以及MT 10 mg/kg 随后给予CBD 2 mg/kg 。使用非房室模型计算药代动力学参数，并进行分析以研究CBD与MT之间的相互作用。CBD和MT的校准曲线在2至1000 ng/mL范围内呈线性。口服高剂量CBD（40 mg/kg）可使MT（10 mg/kg）的Cmax降低至对照组的57%，而0.5至8小时的曲线下面积（AUC）是仅给予MT组的2.85倍。当静脉注射CBD（2 mg/kg）与口服MT同时给药时，AUC是单独口服MT的1.54倍。CBD的AUC与MT分布和消除相的AUC呈正相关，而CBD的Cmax与MT的Cmax呈负相关。所开发的LC - MS/MS方法稳健，适用于涉及CBD和MT的药代动力学研究。CBD对MT药代动力学的体内影响较为复杂。高口服剂量的CBD抑制MT的肠道吸收和代谢清除，从而导致更平稳的药代动力学曲线。
