Identification and characterization of in vitro, in vivo, and reactive metabolites of tandutinib using liquid chromatography ion trap mass spectrometry

2021 ◽  
Author(s):  
Nasser S. Al-Shakliah ◽  
Mohamed W. Attwa ◽  
Haitham AlRabiah ◽  
Adnan A. Kadi
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Ion Trap ◽  
Reactive Metabolites ◽  
Ion Trap Mass Spectrometry ◽  
Identification And Characterization

Ten metabolites and five cyano adducts of TND were characterized using LC-ITMS. All metabolic and bioactivation reactions occurred at the N-piperidine and piperazine groups, which were predicted to be responsible for the TND toxicity and instability.

scholarly journals Detection and Structural Characterization of Nucleophiles Trapped Reactive Metabolites of Limonin Using Liquid Chromatography-Mass Spectrometry

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yujie Deng ◽  
Yudong Fu ◽  
Shumin Xu ◽  
Ping Wang ◽  
Nailong Yang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Ion Trap ◽  
Structural Information ◽  
Enzyme Inactivation ◽  
Reactive Metabolites ◽  
Liquid Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry

Limonin (LIM), a furan-containing limonoid, is one of the most abundant components of Dictamnus dasycarpus Turcz. Recent studies demonstrated that LIM has great potential for inhibiting the activity of drug-metabolizing enzymes. However, the mechanisms of LIM-induced enzyme inactivation processes remain unexplored. The main objective of this study was to identify the reactive metabolites of LIM using liquid chromatography-mass spectrometry. Three nucleophiles, glutathione (GSH), N-acetyl cysteine (NAC), and N-acetyl lysine (NAL), were used to trap the reactive metabolites of LIM in in vitro and in vivo models. Two different types of mass spectrometry, a hybrid quadrupole time-of-flight (Q-TOF) mass spectrometry and a LTQ velos Pro ion trap mass spectrometry, were employed to acquire structural information of nucleophile adducts of LIM. In total, six nucleophile adducts of LIM (M1–M6) with their isomers were identified; among them, M1 was a GSH and NAL conjugate of LIM, M2–M4 were glutathione adducts of LIM, M5 was a NAC and NAL conjugate of LIM, and M6 was a NAC adduct of LIM. Additionally, CYP3A4 was found to be the key enzyme responsible for the bioactivation of limonin. This metabolism study largely facilitates the understanding of mechanisms of limonin-induced enzyme inactivation processes.

Application of liquid chromatography/ion trap mass spectrometry to the characterization of the related substances of clarithromycin

2006 ◽  
Vol 20 (20) ◽  
pp. 3101-3110 ◽  
Author(s):  
Stefanie Leonard ◽  
Monica Ferraro ◽  
Erwin Adams ◽  
Jos Hoogmartens ◽  
Ann Van Schepdael
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Ion Trap ◽  
Ion Trap Mass Spectrometry ◽  
Related Substances
Sign in / Sign up

Export Citation Format

Share Document