ascorbic-acid and 1-nitrosopiperazine

The secondary amine piperazine may be nitrosated in vivo, following oral intake or occupational exposure by inhalation. The suspected carcinogen N-mononitrosopiperazine could be formed in the human stomach, and in part excreted in the urine. In this study, 0.4 microgram N-mononitrosopiperazine, determined by gas chromatography-Thermal Energy Analysis, was observed in the urine in one of four volunteers, at an experimental exposure by inhalation of 0.3 mg piperazine/m3. The intake of spinach and beetroot caused an increased nitrosation of piperazine, and up to 1.7 microgram N-mononitrosopiperazine was excreted in the urine in the four individuals. This excretion indicates that about 5% of the absorbed piperazine dose was converted to N-mononitrosopiperazine. With the same nitrate-rich diet, but with the addition of citrus fruits and fresh vegetables, the highest excretion was 0.6 microgram N-mononitrosopiperazine. The excretion was significantly correlated with the ratio between the maximum level of nitrite in saliva and the ascorbate level in plasma. There was also a significant interindividual variation. N,N'-Dinitrosopiperazine was not found in any sample of urine.

Topics: Administration, Inhalation; Adult; Air Pollutants; Ascorbic Acid; Carcinogens; Diet; Humans; Male; Middle Aged; Nitrates; Nitrites; Nitrosamines; Piperazine; Piperazines; Saliva

Piperazine, a secondary amine widely used as an anthelmintic drug, nitrosates rapidly in vitro to form two N-nitrosamines. Anhydrous piperazine and a drug formulation were found to have a content of 0.2 to 20 micrograms of the suspected carcinogen N-mononitrosopiperazine per gram piperazine, but no detectable amounts of the carcinogen N,N'-dinitrosopiperazine. The aim of this study was to investigate the possible nitrosation of the drug piperazine in man. Thirty minutes after oral administration of 480 mg piperazine to four fasting, healthy, male volunteers, gastric juice contained 140 to 230 micrograms/liter N-mononitrosopiperazine as determined by gas chromatography-thermal energy analysis. The total amount produced by endogenous formation in the stomach is estimated to have been 30 to 66 micrograms. N-Mononitrosopiperazine was not detected in blood, but was excreted in the urine, mainly in the first 6 hr (0.07 to 2.1 micrograms) with half of this appearing within 3 hr. Internal acidification of the urine did not affect the excretion or content. N,N'-Dinitrosopiperazine was not found in any sample of gastric juice, blood, or urine. The excretion of piperazine was in accordance with earlier findings. Coadministration of 2 g ascorbic acid resulted in a significant but incomplete and varying inhibition of both the nitrosation in the stomach and the excretion in urine.

Topics: Administration, Oral; Adult; Animals; Ascorbic Acid; Chromatography, Gas; Drug Combinations; Gastric Juice; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Nitrosamines; Piperazine; Piperazines