Metabolite profiling of l‐isocorypalmine in rat urine, plasma, and feces after oral administration using high performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry

Abstract

l‐Isocorypalmine, an active alkaloid compound isolated from Rhizoma Corydalis yanhusuo, has been reported to possess biological activity for treating cocaine use disorder. A high‐performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry method was established for identification of the metabolites of l‐isocorypalmine in urine, plasma and feces samples of rats after a single intragastric gavage of l‐isocorypalmine at a dose of 15 mg/kg. As a result, a total of 21 metabolites (six phase І metabolites and fifteen phase II metabolites) were detected and tentatively identified by mass spectrometry and fragment ions from tandem mass spectrometry spectra. All metabolites were present in the urine samples, nine metabolites were found in the plasma samples and three metabolites were found in the feces samples. Results indicated that metabolic pathways of l‐isocorypalmine included oxidation, dehydrogenation, demethylation, sulfate conjugation, and glucuronide conjugation. In addition, glucuronidation was the major metabolic reaction. Results of this investigation could provide significant experimental basis for efficacy, safety and action mechanism of l‐isocorypalmine, which will be advantageous to new drug development for treating cocaine addiction.

Pharmacokinetic study of three different formulations of l‐tetrahydropalmatine in brain tissues of rats

“…Extensive studies during several decades indicate that dopamine (DA) is one of the most critical neurotransmitters involved in drug reward and addiction (Wang et al, 2017a). Nowadays a large number of studies focus on candidate drugs to regulate dopaminergic mechanisms and further concentrate on the drugs that function as D3 DA receptor antagonists, D1 partial agonists and more complex pharmacological profiles with differential roles in various receptor types and positions (Li et al, 2019).…”

Metabolic profiling of ligustilide and identification of the metabolite in rat and human hepatocytes by liquid chromatography combined with high‐resolution mass spectrometry

“…Drug metabolism is one of the main routes of drug elimination from body, and it also plays an increasingly important role in drug discovery and development. Identification of metabolite(s) of a potential drug candidate provides key information on drug efficacy and toxicological profiles [11][12][13]. Several studies on the metabolism of ligustilide have been performed.…”