摘要：

Abstract 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′-¹⁴C]cotinine and other radiolabeled metabolites such as [2′-¹⁴C]nornicotine and [4-¹⁴C]-(3-pyridyl)-4-oxobutyric acid, from commercially available [2′-¹⁴C]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′-<em>N</em>-oxide and cotinine-1-<em>N</em>-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.

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