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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(02): e103-e112
DOI: 10.1055/s-0042-1749081
Original Article

Development of a UPLC-MS/MS Method for Pharmacokinetic and Tissue Distribution of Isoeleutherin, Eleutherin, and Eleutherol in Bulbus eleutherinis in Rats

Peng-Cheng Guo‡   #
1   Functionalized DDS and New Drug Development Research Group, School of Pharmacy, Shanghai Jiao Tong university, Shanghai, People's Republic of China
,
Jie-Yu Chen‡   #
1   Functionalized DDS and New Drug Development Research Group, School of Pharmacy, Shanghai Jiao Tong university, Shanghai, People's Republic of China
,
Jing Su‡   #
1   Functionalized DDS and New Drug Development Research Group, School of Pharmacy, Shanghai Jiao Tong university, Shanghai, People's Republic of China
,
Faisal Raza
1   Functionalized DDS and New Drug Development Research Group, School of Pharmacy, Shanghai Jiao Tong university, Shanghai, People's Republic of China
,
Bin Hao
1   Functionalized DDS and New Drug Development Research Group, School of Pharmacy, Shanghai Jiao Tong university, Shanghai, People's Republic of China
,
Xin-Yi Wu
1   Functionalized DDS and New Drug Development Research Group, School of Pharmacy, Shanghai Jiao Tong university, Shanghai, People's Republic of China
,
Yi-Qing Cheng
2   Indian Springs School, Indian Springs, Alabama, United States
,
Ming-Feng Qiu
1   Functionalized DDS and New Drug Development Research Group, School of Pharmacy, Shanghai Jiao Tong university, Shanghai, People's Republic of China
› Author Affiliations Funding This research was supported by the Shanghai Committee of Science and Technology (Grant No. 17401900900 and 15401901700), the National Natural Science Foundation of China (Grant No. 81973487 and 81573617), and National Facility for Translational Medicine (Shanghai) with Grant No. TMSK-2020-110.
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Abstract

Bulbus eleutherinis is a classical traditional Dai medicine, and has been widely used in clinical treatment of coronary heart disease (CHD) in Yunnan, China. Naphthoquinone, as the main active compound in Bulbus eleutherinis in treating CHD, mainly contain isoeleutherin, eleutherin, and eleutherol. This study aimed to investigate the in vivo parameters of isoeleutherin, eleutherin, and eleutherol. In this work, male Sprague Dawley (SD) rats were treated with the three compounds by oral administration, and then blood and tissue samples were collected. A novel UPLC-MS/MS (ultra-performance liquid chromatography-tandem mass spectrometry) method has been developed to determine the absolute oral bioavailability, and the tissue distribution profile of the compounds. Acetonitrile and 0.1% (v/v) solution of formic acid were selected as the mobile phase of the chromatogram. C18 column was employed. Betamethasone was used as an internal standard in the method. The detection was performed with a multireaction monitor of scan type in positive ion mode by MS/MS. Our data showed linearity of the method with r over 0.9983. Lower limits of quantification of isoeleutherin, eleutherin, and eleutherol were 1.00, 3.84, and 0.498 ng/mL, respectively. The overall precision of the compounds was less than 12.68%, recoveries ranged from 85.44 to 103.83%, and the accuracy of the compounds in plasma was between 91.56 and 110.75%. The stability assay showed that they were stable (87.83–114.62%) under different conditions in plasma. For oral administration, the half-lives of isoeleutherin, eleutherin, and eleutherol was 6.11, 7.30, and 3.07 hours, respectively. The absolute oral bioavailabilities were 5.38, 4.64, and 2.47%, respectively. Moreover, the three components had the highest distribution in small intestine. In conclusion, the established method was successfully applied to the determination of the in vivo parameters of the three components in SD rats. This work provides a reference for the development of new drugs of Bulbus eleutherinis in the future.

Keywords

Bulbus eleutherinis - UPLC-MS/MS - naphthoquinone - pharmacokinetics - tissue distribution

# These authors contributed equally to this work.




Publication History

Received: 17 December 2021

Accepted: 12 April 2022

Article published online:
30 June 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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