Skip to main content
ARS Home » Plains Area » College Station, Texas » Southern Plains Agricultural Research Center » Food and Feed Safety Research » Research » Publications at this Location » Publication #311211
Title: Comparative metabolism of Lappaconitine in rat and human liver microsomes and in vivo of rat using ultra high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry

Author
item YANG, SHUPENG - China Agricultural University
item ZHANG, HUIYAN - China Agricultural University
item Beier, Ross
item SUN, FEIFEI - China Agricultural University
item CAO, XINGYUAN - China Agricultural University
item SHEN, JIANZHONG - China Agricultural University
item WANG, ZHANHUI - China Agricultural University
item ZHANG, SUXIA - China Agricultural University

Submitted to: Journal of Pharmaceutical and Biomedical Analysis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/26/2015
Publication Date: 3/6/2015
Publication URL: https://handle.nal.usda.gov/10113/5508066
Citation: Yang, S., Zhang, H., Beier, R.C., Sun, F., Cao, X., Shen, J., Wang, Z., Zhang, S. 2015. Comparative metabolism of Lappaconitine in rat and human liver microsomes and in vivo of rat using ultra high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. 110:1-11.

Interpretive Summary: Lappaconitine is a natural occurring diterpenoid alkaloid extracted from the plant Aconitum sinomontanum. Lappaconitine has a wide range of biological activities, and among those it is antiarrhythmic, has a strong anti-inflammatory effect, and is antibacterial against Pseudomonas aeruginosa and Salmonella typhi. The potential for new antibiotic development opportunities is very important and should be pursued. However, lappaconitine’s metabolism in humans and animals is not well understood. To help understand its metabolism in animals better and to expand its usefulness, this study was conducted to determine the expected metabolite profiles in the rat and human. As a result of the work, a total of 51 metabolites were identified. The biotransformations of lappaconitine involved five different types of metabolic reactions. This work provides the lappaconitine metabolite profiles in the rat and human, which help to better understand the pharmacological and toxicological activities of lappaconitine.

Technical Abstract: Lappaconitine (LAP) is a non-addictive potent analgesic drug broadly used to treat severe cancer pain and postoperative pain in many countries around the world, and it also has antibiotic activity against Pseudomonas aeruginosa and Salmonella typhi. Despite its widespread usage and potential for expanded use, its metabolism has been poorly investigated. In this work, the metabolic fate of LAP in liver microsomes of the rat and human was compared, and after oral administration the metabolites in the rat were investigated using ultra-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC–Q/TOF-MS). As a result, a total of 51 metabolites were identified, including 48 metabolites that were reported here for the first time. Based on accurate MS/MS spectra and the known structure of LAP, the metabolites structures and their fragment ions were readily characterized. The biotransformations of LAP in vitro and in vivo were shown to involve hydroxylation, N-deacetylation, O-demethylation, N-deethylation, and hydrolysis. Furthermore, the results indicated a quantitative species difference in the metabolites for LAP between the rat and human. However, 16-DMLAP, DAL, and 5’-OH-DAL were the main in vitro and in vivo metabolites. This work provides the LAP metabolite profiles in the rat and human, which help to better understand the pharmacological and toxicological activities of LAP.