Determination of Daphnetin and its 8-O-Methylated Metabolite in Rat Plasma by UFLC-MS/MS: Application to a Pharmacokinetic Study
2022
Wang, Zhongqiong | Wang, Chengyi | He, Bing | Zhang, Wei | Liu, Li | Deng, Mingming | Lü, Muhan | Qi, Xiaoyi | Liang, Sicheng
Daphnetin, which has been developed as a drug against obliterative vasculitis, can be rapidly and stereoselectively metabolized to an active 8-O-methylated metabolite, namely daphnetin 8-methyl ether (daphnetin-Me). Herein, a rapid, sensitive and reliable ultrafast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was developed and validated to simultaneously determine daphnetin and daphnetin-Me in rat plasma after intragastric administration. The MS quantification for the two analytes and 3-aminocoumarin (internal standard, IS) was carried out on a triple quadrupole mass spectrometer using an ESI source in positive multiple reaction monitoring mode (daphnetin: m/z 179.15 → 51.10; daphnetin-Me: m/z 193.30 → 150.05; IS: m/z 162.00 → 106.20). The method exhibited a broad linear range of 1–2000 ng mL⁻¹. The intra- and inter- assay precisions (RSD%) were ≤ 8.29% with the accuracies (RME%) within ± 5.95%. This newly developed method was successfully applied to a pharmacokinetic study of daphnetin after a single dose of 20 mg kg⁻¹ in rats. Daphnetin and daphnetin-Me peaked almost at the same time. Compared with that of daphnetin, a 2.1-fold higher area under the concentration–time curve (AUC) for daphnetin-Me were observed. These results would be beneficial in facilitating further investigation of pharmacological mechanisms, as well as the rational application of daphnetin and daphnetin-containing herb preparations.
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