Premium
The biosynthesis of [5′‐ 14 C]cotinine and other radiolabeled nicotine metabolites
Author(s) -
Tsai MuiChiung,
Sai Yang,
Li Yan,
Aislaitner George,
Gorrod John W.
Publication year - 1999
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199904)42:4<387::aid-jlcr203>3.0.co;2-5
Subject(s) - nornicotine , cotinine , chemistry , nicotine , chromatography , metabolite , biosynthesis , biochemistry , high performance liquid chromatography , alkaloid , stereochemistry , enzyme , medicine
The present study describes the biosynthesis and isolation of the major radiolabeled nicotine metabolites formed using phenobarbitone (PB)‐induced rabbit hepatic homogenates (10,000 g fraction). The optimal incubation and extraction methods for cotinine formation from non‐labeled nicotine were established. The biosynthesis and isolation of [5′‐ 14 C]cotinine and other radiolabeled metabolites such as [2′‐ 14 C]nornicotine and [4‐ 14 C]‐(3‐pyridyl)‐4‐oxobutyric acid, from commercially available [2′‐ 14 C]nicotine, were carried out using the developed methods. Cotinine was isolated using preparative silica gel TLC, whereas the other metabolites were obtained using a cation‐exchange HPLC method. This study showed that in addition to the two major metabolites (i.e. cotinine and nornicotine), 4‐(3‐pyridyl)‐4‐oxo‐butyric acid, 3‐hydroxycotinine, norcotinine, nicotine‐1′‐ N ‐oxide and cotinine‐1‐ N ‐oxide were also formed when PB‐induced rabbit hepatic homogenates were used. Two further metabolites of unknown structure were detected. However, the isolation and further purification were only carried out on cotinine, nornicotine and 4‐(3‐pyridyl)‐4‐oxo‐butyric acid. Copyright © 1999 John Wiley & Sons, Ltd.