Objective: To establish a UPLC-Q TOF-MS method for the determination of emodin-type monoanthrone and its metabolites in plasma, and to study the toxicokinetic (TK) behavior of its prototype and metabolites in rats. Methods: The TK of the prototype and its metabolites from the first administration to the end of administration was determined in the repeated-dosed toxicity study.The mobile phase was acetonitrile(A)-0.1% formic acid(B), gradient elution(0-7 min, 95%A→50%A; 7-10 min, 50%A→20%A; 10-11 min, 20%A→0%A) negative ion scanning mode.Current speed was 0.4 mL·min-1. Column temperature was 40 ℃. Capillary voltage 1.0 kV, taper hole voltage 30 V, scanning range m/z 50-1 000 the kinetic parameters Tmax, Cmax, AUCall and MRTlast were calculated. Degrees of exposure of the prototype and metabolites in the plasma of rats after oral administration of different doses of emodin-type monoanthrone were evaluated. Results: In this study, after the administration of emodin-type monoanthrone, the Cmax of prototype components in rats were 0.56 μg·mL-1 (high concentration administration), 0.54 μg·mL-1(medium concentration administration) and 0.51 μg·mL-1(low concentration administration), AUCall in vivo were 1.13 h·μg·mL-1(high concentration administration), 1.11 h·μg·mL-1 (medium concentration administration), 1.18 h·μg·mL-1(low concentration administration), there was no significant difference in the plasma exposure of the prototype in rats, and its main metabolites were anthraquinone (emodin, hydroxyemodin, aloe-emodin) and anthracene quinone glycosides (emodin-8-O-β-D-glucoside, aloe-emodin-8-O-β-D-glucoside), the prototype and most metabolites were generally stay in the body for 20 h. Aloe-emodin, hydroxy-emodin and emodin appeared mild accumulation along with the increased doses. Conclusion: After administration of emodin-type monoanthrone, the prototype and its metabolites are eliminated slowly in the body. Therefore, the administration dose and interval of emodin-type monoanthrone should be strictly controlled to prevent adverse reactions from accumulation in the body.
WANG Qi, YANG Jian-bo, WANG Ying, LI Yan-yi, ZHANG Yu-yie, WEN Hai-ruo, MA Shuang-cheng
. Toxicokinetics study of monanthone in rats in vivo*[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(10)
: 1720
-1728
.
DOI: 10.16155/j.0254-1793.2022.10.05
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