Gas chromatography-high resolution mass spectrometry methods were developed for quantifying nitrosodimethylamine (NDMA) and nitrosoproline (NPRO) in human urine. The limits of quantitation of these methods, which utilize stable isotope analogues of NDMA and NPRO as internal standards, were 5 pg per ml for NDMA and 0.14 ng per ml for NPRO. The assays were used to quantify NDMA and NPRO in urine samples collected 4 times a wk for 5 wk from 24 healthy volunteers. The mean urinary excretion of NDMA during this time was found to be 38.2 ng per day, and the mean urinary excretion of NPRO was found to be 3.26 micrograms per day. Treatment of the volunteers with 600 mg of ascorbic acid and 100 IU of alpha-tocopherol 4 times a day for the final 3 wk of the study did not influence the urinary excretion of NDMA or NPRO. Considerable person-to-person and day-to-day variations were observed for the urinary excretion of both nitrosamines, but the urinary excretion of NDMA was not correlated with the urinary excretion of NPRO. Person-to-person and day-to-day differences in the urinary excretion were greater for NPRO than for NDMA. The mean urinary excretion of NDMA by the 24 subjects was as much as 5-fold higher on some days than on other days, but this was not observed for NPRO. Day-to-day differences in the mean urinary excretion of NDMA were correlated with the concentrations of nitrogen dioxide in the air.

Nitrosamine

N-Nitrosodimethylamine

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Citations (48)

Determination of acetyltrimoprostil and its metabolite trimoprostil in human or dog plasma by gas chromatography—negative-ion chemical ionization mass spectrometry

Journal of Chromatography B Biomedical Sciences and Applications (1985)

F. Rubio William A. Garland

Selected ion monitoring

Dichloromethane

10.1016/s0378-4347(00)84658-7

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Citations (7)

Disposition of [14C]acitretin in humans following oral administration.

Drug Metabolism and Disposition (1994)

F. Rubio Bradford K. Jensen L Henderson William A. Garland Alice J. Szuna

The disposition of the antipsoriatic agent, acitretin, was investigated in six healthy human volunteers who each received a single, oral 50 mg dose of [14C]acitretin (50 microCi). plasma, urine, and feces were collected for 240 hr after administration. Mean values of 20.9 and 62.6% of the administered dose were recovered in the urine and feces, respectively. The terminal elimination half-life of total radioactivity from the plasma was approximately 120 hr. Extraction of pooled plasma samples followed by separation by HPLC and quantitation by liquid scintillation counting indicated that acitretin and its 13-cis-isomer, isoacitretin, were minor fractions of the total drug-related material in the plasma at most time points up to 72-hr postdose. The structures of acitretin, isoacitretin, and two other metabolites--(5E,7E)-8-(4-methoxy,2,3,6-trimethylphenyl)-2,6 -dimethyl-5,7- octadienoic acid (I) and (5E,7E)-8-(4-hydroxy-2,3,6-trimethylphenyl)-2,6-dimethyl-5,7 -octadienoic acid (II)--were confirmed by MS and cochromatography with authentic standards. I and II were major fractions of the drug-related material in the plasma at all time points. Other compounds, whose structures could not be confirmed, also account for a significant fraction of the circulating radioactivity.

Acitretin

Free fraction

Half-life

Blood plasma

10.1016/s0090-9556(25)08360-6

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Citations (10)