Abstract
Background: Scoparone, the principal natural active ingredient of Artemisia capillaries (Yin Chen), can effectively treat cholestatic diseases, but the pharmacokinetic properties of scoparone are rarely studied in intrahepatic cholestatic rats.
Objective: A sensitive and rapid LC-MS/MS method was established to detect scoparone and its metabolite of scopoletin in rat plasma and then compare their plasma pharmacokinetic differences between the normal and ANITinduced cholestasis rats.
Methods: Positive ionization was used to separate scoparone and scopoletin using acetonitrile and 0.1 % formic acid water as the mobile phase on a Hypersil ODS-BP column.
Results: The calibration curves presented good linearity (R=0.9983 and 0.9989) in the concentration range of 10- 10000 ng/mL and 0.5-500 ng/mL for scoparone and scopoletin, respectively. The precision of ≤ 9.4% and the accuracy ranged from -6.4% to 6.8% were recorded over three validation runs, and the recovery was higher than 83.9%. Under different storage conditions, scoparone and scopoletin were stable. Therefore, we studied the pharmacokinetic properties of scoparone and scopoletin in rats after a single oral administration with the above method. According to the results, the pharmacokinetic parameters of AUC, t1/2, and Cmax values of scoparone in the ANIT group were increased by 106%, 75%, and 44%, respectively, while these values of scopoletin were increased by 142%, 62%, and 65%.
Conclusion: The findings indicated that the pharmacokinetic properties of scoparone and scopoletin were significantly different between the normal and ANIT-induced cholestasis rats, which suggested that the clinical application dosage of scoparone should be adjusted according to the liver function of patients.
Graphical Abstract
[http://dx.doi.org/10.1186/s12929-018-0475-8] [PMID: 30367658]
[http://dx.doi.org/10.1002/hep.31430] [PMID: 32583448]
[http://dx.doi.org/10.1016/j.jpha.2020.05.005] [PMID: 32612873]
[http://dx.doi.org/10.1016/j.mayocp.2020.01.015] [PMID: 33012354]
[http://dx.doi.org/10.12659/MSM.894043] [PMID: 26467199]
[http://dx.doi.org/10.2147/PGPM.S107152] [PMID: 28790862]
[http://dx.doi.org/10.1016/j.jep.2015.03.058] [PMID: 25849734]
[http://dx.doi.org/10.1111/j.1476-5381.2011.01522.x] [PMID: 21649640]
[http://dx.doi.org/10.1172/JCI200418385] [PMID: 14702117]
[http://dx.doi.org/10.1016/0306-3623(95)02112-4] [PMID: 8853310]
[http://dx.doi.org/10.1055/a-0835-2301] [PMID: 30736072]
[http://dx.doi.org/10.1007/s11655-012-1272-8] [PMID: 23086487]
[http://dx.doi.org/10.1016/j.fitote.2012.03.010] [PMID: 22465507]
[http://dx.doi.org/10.1016/j.phymed.2008.01.006] [PMID: 18339526]
[http://dx.doi.org/10.1002/bmc.1739] [PMID: 22068685]
[PMID: 18751499]
[http://dx.doi.org/10.1016/j.jep.2015.07.037] [PMID: 26231452]
[http://dx.doi.org/10.1093/jac/dku457] [PMID: 25587994]
[http://dx.doi.org/10.1002/bmc.3182] [PMID: 24806456]
[http://dx.doi.org/10.3109/10717544.2013.876561] [PMID: 24447164]
[http://dx.doi.org/10.1089/omi.2012.0064] [PMID: 23514563]
[http://dx.doi.org/10.3390/molecules23102716] [PMID: 30360359]
[PMID: 20662310]
[http://dx.doi.org/10.1002/rcm.3296] [PMID: 17979104]
[http://dx.doi.org/10.1016/j.jep.2015.12.033] [PMID: 26723467]
[http://dx.doi.org/10.1016/0006-2952(93)90648-G] [PMID: 8267654]
[http://dx.doi.org/10.1016/j.jep.2016.12.022] [PMID: 27988401]
[http://dx.doi.org/10.1093/mutage/gei001] [PMID: 15598703]
[http://dx.doi.org/10.1055/s-0043-119886] [PMID: 28950382]
[http://dx.doi.org/10.1016/j.cbi.2015.09.012] [PMID: 26365562]
[http://dx.doi.org/10.1016/j.phrs.2020.105170] [PMID: 32877694]