Pharmacokinetic Study and Metabolite Identification of 1-(3'-bromophenyl)-heliamine in Rats

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 15; no. 12; p. 1483
• Main Authors: Xi, Ruqi, Abdulla, Rahima, Zhang, Miaomiao, Sherzod, Zhurakulov, Ivanovna, Vinogradova Valentina, Habasi, Maidina, Liu, Yongqiang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.11.2022; MDPI
• Subjects: Amines; Bioavailability; Cardiac arrhythmia; Cardiovascular agents; Cardiovascular disease; Chemical properties; Circulatory system; Health aspects; Hydrocarbons; Identification and classification; in silico metabolite prediction; LC−MS/MS; Metabolism; Metabolites; Oral administration; Pharmaceutical research; pharmacokinetic; Pharmacokinetics; Plasma; rats; China; Uzbekistan; rats; pharmacokinetic; metabolites; LC−MS/MS; in silico metabolite prediction
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph15121483

Tetrahydroisoquinolines have been widely investigated for the treatment of arrhythmias. 1-(3'-bromophenyl)-heliamine (BH), an anti-arrhythmias agent, is a synthetic tetrahydroisoquinoline. This study focuses on the pharmacokinetic characterization of BH, as well as the identification of its metabolites, both in vitro and in vivo. A UHPLC-MS/MS method was developed and validated to quantify BH in rat plasma with a linear range of 1-1000 ng/mL. The validated method was applied to a pharmacokinetic study in rats. The maximum concentration C (568.65 ± 122.14 ng/mL) reached 1.00 ± 0.45 h after oral administration. The main metabolic pathways appeared to be phase-I of demethylation, dehydrogenation, and epoxidation, and phase II of glucuronide and sulfate metabolites. Finally, a total of 18 metabolites were characterized, including 10 phase I metabolites and 8 phase II metabolites. Through the above studies, we have gained a better understanding of the absorption and metabolism of BH in vitro and in vivo, which will provide us with guidance for future in-depth studies on this compound.