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Dedicated to Professor Dr G. SpiteUer on the occasion of his 60th birthday N-Acetylcysteine and nine N-acetylcysteine conjugates of synthetic origin were characterized by positive-and negative-ion plasma desorption mass spectrometry. For sample preparation the electrospray technique and the nitrocellulose spin deposition technique were applied. The fkagmentation of these compounds, which are best seen as S-substituted desaminoglycylcysteiae dipeptides, shows a similar behaviour to that of linear peptides. In the positive-ion mass spectra intense protonated molecular ion peaks are observed. In addition, several sequence specific fragment ions (A+, B+, IY + 2H]+, Z'), immonium ions (I+) and a diagnostic fragment ion for mercap turic acids %+) are detected. The negative-ion mass spectra exhibit deprotonated molecular ions and in contrast only one fragment ion corresponding to sidechain specific cleavage ([ R,S] -) representing the xenobiotic moiety.In the case of a low alkali metal concentration on the target, cluster molecular ions of the [nM + HI+ or InM -H]ion type (n = 1-3) are observed. The analysis of an equimolar mixture of eight N-acetylcysteine conjugates shows diaerent quasi-molecular ion yields for the positiveand negative-ion spectra.

The potential endogenous nitrosation of nicotine and cotinine to yield 4-(N-methylnitrosamino)-4-(3-pyridyl)butyric acid (Iso-NNAC) has been studied in smokers and non-smokers. Following i.v. administration of 100 micrograms Iso-NNAC to rats, excretion in urine (67.4 +/- 25.4%) and feces (6.1 +/- 1.6%) occurred within 24 h. The urinary excretion of nitrate, nicotine, cotinine and Iso-NNAC were determined in 24 h urine samples from 19 smokers and 10 non-smokers. Iso-NNAC excretion was found on four occasions (44, 65, 74 and 163 ng/day) in smokers; non-smokers did not excrete Iso-NNAC. Oral administration of nicotine (n = 8; 12-40 mg) and cotinine (n = 3; 40-60 mg) to abstinent smokers did not result in Iso-NNAC excretion, even after oral nitrate (150 mg) supplementation. However, Iso-NNAC was found in cigarette tobacco (10-330 ng/g) and mainstream cigarette smoke (1.1-5.5 ng/cig.). Our studies suggest that the occasional presence of Iso-NNAC in smokers' urine results from exogenous exposure to the preformed compound in mainstream cigarette smoke and not from endogenous nitrosation of nicotine and its metabolites.

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