Chao Ma, Dan Li, Rui Dang
Oct 31, 2022
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Quality indicators
Journal
Biomedical chromatography : BMC
Abstract
Yuanhuacine is a daphne-type diterpene ortho-ester and originated from genkwa flos. Anti-cancer activity of yuanhuacine have been well investigated on various tumor cells and animal models, but information about metabolism and pharmacokinetics is limited. The aims of the present study were to investigate metabolic and pharmacokinetic profiles of yuanhuacine in rat. The metabolic profile of yuanhuacine was obtained from rat plasma, urine, and feces using an ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry. Total 7 metabolites were detected, and the proposed metabolic pathways involved oxidation and glucuronidation. A simple and sensitive ultra-high performance liquid chromatography tandem mass spectrometry method was developed for determination of yuanhuacine in rat plasma. The linear range of yuanhuacine was 1-1000 ng/mL (R2 = 0.998). The intra- and inter-precision (CV%) of the assay were 3.86%-6.18% and 2.65%-5.75%, and the intra- and inter-accuracy (RE%) were -3.83%-4.77% and -3.03%-5.11%, respectively. The extraction recovery, matrix effect, stability, and incurred sample reanalysis of yuanhuacine were within acceptable levels. The established method was validated and successfully applied to the preclinical pharmacokinetic study of yuanhuacine. The absolute oral bioavailability of yuanhuacine was calculated as 1.14%, and it reached the maximum plasma concentration of 28.21 ± 2.79 ng/mL in rat plasma at 2 h for oral dosing group. The apparent volume of distribution of intravenous and intragastric administrations were 26.07 ± 6.45 L/kg and 21.83 ± 3.54 L/kg, respectively. The half-life of elimination of yuanhuacine was 9.64 ± 1.53 h in intravenous dosing group.