Pharmacokinetics and Tissue Distribution of Anwuligan in Rats after Intravenous and Intragastric Administration by Liquid Chromatography-Mass Spectrometry

• Published in: Molecules (Basel, Switzerland) Switzerland), 2019-12, Vol.25 (1), p.39
• Main Authors: Song, Yang, Zhang, Yuan, Duan, Xiao-Yi, Cui, Dong-Wei, Qiu, Xin, Bian, Yu, Wang, Ke-Fei, Feng, Xue-Song
• Format: Article
• Language: English
• Subjects: Accuracy; Acetic acid; Acetonitrile; Administration, Intravenous; Animals; Aqueous solutions; Bacteria; Bioavailability; Calibration; Cancer therapies; Diabetes; Drug dosages; Ethyl acetate; Formic acid; Intravenous administration; Ionization; Kinases; Lignans; Lignans - chemistry; Lignans - pharmacokinetics; Lignans - pharmacology; Liquid chromatography; Liquid-liquid extraction; Liver; Liver - metabolism; Male; Mass spectrometry; Mass spectroscopy; Myristica - chemistry; Nutmeg; Oral administration; Pharmacokinetics; Pharmacology; Plasma; Proteins; Rats; Rats, Sprague-Dawley; Reagents; Sample preparation; Spectroscopy; Tissue Distribution; Tissues; Tumor necrosis factor-TNF
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25010039

Anwuligan, a natural 2,3-dibenzylbutane lignan from the nutmeg mace of , has been proved to possess a broad range of pharmacological effects. A rapid, simple, and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been established and successfully applied to the study of pharmacokinetics and tissue distribution of anwuligan after intravenous or intragastric administration. Sample preparation was carried out through a liquid-liquid extraction method with ethyl acetate as the extraction reagent. Arctigenin was used as the internal standard (IS). A gradient program was employed with a mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile. The mass spectrometer was operated in a positive ionization mode with multiple reaction monitoring. The transitions for quantification were / 329.0→205.0 for anwuligan and / 373.0→137.0 for IS, respectively. Calibration curves were linear over the ranges of 0.5-2000 ng/mL for both plasma samples and tissue samples (r > 0.996). The absolute bioavailability is 16.2%, which represented the existing of the obvious first-pass effect. An enterohepatic circulation was found after the intragastric administration. Anwuligan could be distributed rapidly and widely in different tissues and maintained a high concentration in the liver. The developed and validated LC-MS/MS method and the pharmacokinetic study of anwuligan would provide reference for the future investigation of the preclinical safety of anwuligan as a candidate drug.