Identification in rats of N-nitrosonipecotic acid as a major urinary metabolite of the areca-nut alkaloid-derived nitrosamines, N-nitrosoguvacoline and N-nitrosoguvacine

N-Nitrosamines derived from areca-nut alkaloids have been implicated in cancer of the oral cavity and esophagus caused by betel quid chewing in India and other Asian countries. A major urinary metabolite of N-nitrosoguvacoline and N-nitrosoguvacine, both present in saliva of betel quid chewers of ppb levels, was isolated from rat urine and identified as N-nitrosonipecotic acid by comparison with the authentic compound. When a dose of 50 or 500 μg/rat of either compound was administered orally to BDIV rats, 66-85% of the dose was excreted in the urine as N-nitrosonipecotic acid and 2-8% as N-nitrosoguvacine. These N-nitrosamino acids could be analysed in the urine of betel quid chewers as a marker of exposure to areca-nut specific nitrosamines.