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.
abstract: Lappaconitine (LAP), a non-addictive potent analgesic drug, is broadly used to treat cancer and postoperative pain in many countries, and it also has antibiotic activity against Pseudomonas aeruginosa and Salmonella Typhi. Despite its widespread usage and potential for expanded use, its metabolism was 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 high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-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 rat and human, which will help better understand the pharmacological and toxicological activities of LAP.
authors: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing 100193, People's Republic of China.
authors: Shupeng
authors: S
authors: Yang
authors: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing 100193, People's Republic of China.
authors: Huiyan
authors: H
authors: Zhang
authors: U.S. Department of Agriculture, Agricultural Research Service, Southern Plains Agricultural Research Center, Food and Feed Safety Research Unit, College Station, TX 77845, USA.
authors: Ross C
authors: RC
authors: Beier
authors: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing 100193, People's Republic of China.
authors: Feifei
authors: F
authors: Sun
authors: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing 100193, People's Republic of China.
authors: Xingyuan
authors: X
authors: Cao
authors: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing 100193, People's Republic of China.
authors: Jianzhong
authors: J
authors: Shen
authors: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing 100193, People's Republic of China.
authors: Zhanhui
authors: Z
authors: Wang
authors: College of Veterinary Medicine, China Agricultural University, Beijing Laboratory for Food Quality and Safety, Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing 100193, People's Republic of China. Electronic address: suxia@cau.edu.cn.
authors: Suxia
authors: S
authors: Zhang
mesh_terms: D000107:Acetylation; D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003640:Dealkylation; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D006868:Hydrolysis; D006900:Hydroxylation; D066237:Intestinal Elimination; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D017208:Rats, Wistar; D065667:Renal Elimination; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D018712:Analgesics, Non-Narcotic; D000157:Aconitine; C022150:lappaconitine
keywords: In vivo; Lappaconitine; Liver microsomes; Metabolism; UHPLC–Q/TOF-MS