Elucidation of Degradation Behavior of Tricyclic Antidepressant Amoxapine in Artificial Gastric Juice

• Saito Koichi

  Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University

• Hagiwara Nami

  Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University

• Sakamoto Miho

  Department of Pharmaceutical Sciences, Tokyo Metropolitan Institute of Public Health

• Wakana Daigo

  Department of Bioregulatory Science, Faculty of Pharmaceutical Sciences, Hoshi University

• Ito Rie

  Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University

• Hosoe Tomoo

  Department of Bioregulatory Science, Faculty of Pharmaceutical Sciences, Hoshi University

Abstract

The degradation behavior of eight tricyclic antidepressants (TCAs; amitriptyline, amoxapine (AMX), imipramine, clomipramine, desipramine, doxepin, dothiepin, and nortriptyline) in artificial gastric juice was investigated to estimate their pharmacokinetics in the stomach. As a result, among the eight TCAs, only AMX was degraded in artificial gastric juice. The degradation was a pseudo first-order reaction; activation energy (Ea) was 88.70 kJ/mol and activation entropy (ΔS) was −80.73 J/K·mol. On the other hand, the recovery experiment revealed that the degradation product did not revert to AMX and accordingly, this reaction was considered to be irreversible. In the AMX degradation experiment, peaks considered to be degradation products A (I) and B (II) were detected at retention times of around 3 min and 30 min in LC/UV measurements, respectively. Structural analysis revealed that compound (I) was [2-(2-aminophenoxy)-5-chlorophenyl]-piperazin-1-yl-methanone, a new compound, and compound (II) was 2-chlorodibenzo[b,f][1,4]oxazepin-11(10H)-one. As for the degradation behavior, it was estimated that AMX was degraded into (II) via (I), i.e., (II) was the final product. The results are expected to be useful in clinical chemistry and forensic science, including the estimation of drugs to be used at the time of judicial dissection and suspected drug addiction.

Journal

• Chemical and Pharmaceutical Bulletin

  Chemical and Pharmaceutical Bulletin 68 (9), 848-854, 2020-09-01

  The Pharmaceutical Society of Japan

Keywords

• tricyclic antidepressant
• amoxapine
• degradation pathway
• artificial gastric juice
• HPLC

Details

• CRID: 1390566775163157760
• NII Article ID: 130007893862
• NII Book ID: AA00602100
• DOI: 10.1248/cpb.c20-00313
• ISSN: 13475223
• ISSN: 00092363
• NDL BIB ID: 030605917
• PubMed: 32879225
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I030605917
• Web Site: https://www.jstage.jst.go.jp/article/cpb/68/9/68_c20-00313/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2021209623
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed