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Planta Med 2023; 89(05): 571-579
DOI: 10.1055/a-1915-5456
Pharmacokinetic Investigations
Original Papers

Comparative Pharmacokinetic Study of Two Pyrrolizidine Alkaloids Lasiocarpine and Heliotrine in Rats

Feifei Lin
1   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
2   School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
,
Lijuan Zhao
2   School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
,
Yingying Wang
2   School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
,
Yang Ye
1   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
2   School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
,
Jia Liu
2   School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
› Author AffiliationsSupported by: Science and Technology Commission of Shanghai Municipality 20430780300
Supported by: Key-Area Research and Development Program of Guangdong Province 2020B0303070002
Supported by: National Natural Science Foundation of China 21920102003
Supported by: National Natural Science Foundation of China 81803610
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Abstract

Lasiocarpine (LAS) and heliotrine (HEL) are two different ester types of toxic pyrrolizidine alkaloids (PAs): open-chain diester and monoester. However, the pharmacokinetics of these two types of PAs in rats have not been reported. In the present study, two LC-MS/MS methods for determining LAS and HEL were established and validated. The methods exhibited good linearity, accuracy, and precision and were then applied to a comparative pharmacokinetic study. After intravenous administration to male rats at 1 mg/kg, the AUC0-t values of LAS and HEL were 336 ± 26 ng/mL × h and 170 ± 5 ng/mL × h. After oral administration at 10 mg/kg, the AUC0-t of LAS was much lower than that of HEL (18.2 ± 3.8 ng/mL × h vs. 396 ± 18 ng/mL × h), while the Cmax of LAS was lower than that of HEL (51.7 ± 22.5 ng/mL × h vs. 320 ± 26 ng/mL × h). The absolute oral bioavailability of LAS was 0.5%, which was significantly lower than that of HEL (23.3%). The results revealed that the pharmacokinetic behaviors of LAS differed from that of HEL.

Key words

Lasiocarpine - Heliotrine - pyrrolizidine alkaloid - pharmacokinetics

Supporting Information

    Mass spectra of analytes and ISs, and metabolite screening methods and results are available as Supporting Information.

  • Supporting Information


Publication History

Received: 05 January 2022

Accepted after revision: 27 July 2022

Article published online:
28 September 2022

© 2022. Thieme. All rights reserved.

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