The study of urea metabolism In humans necessitates sen-sitive methods, so that very low Isotopic enrichments of plasma or urinary urea can be measured. A stable derivative of urea, suitable for the measurement of 1SN or 13C enrich-ments of urea using gas chromatography/mass spectrometry, Is described. The trlmethylslloxypyrlmidlne could be iised to measure [1SN2]-and p'N^ urea enrichments as low as 0.5% with a coefficient of variation below 5%. Determination of a lower enrichment of [15N2] urea required the use of 2-trlfluoroacetoxypyrimidine, which had a background of 0.4% at the (+ 2) Ion. The coefficient of variation In determining this background was 1.6%; this means a low enrichment, such as 0.1%, could be determined with confidence. This technique was applied to the study of urea metabolism In humans and dogs.

The quantitationof urea turnover rate in humans has generally been done by isotope tracer dilution techniques (1-3). In these experiments, thenonradioactive tracer,[15N2] urea, is administered to the subject by either single bolus injection or constant infusion. Serial sampling of plasma or urine and the determination of [15N] urea enrichments in these samples provide data for the calculation of turnovérrate. Traditionally, the measurement of [15N] urea enrichments has been accomplishedby using an isotope ratio mass spectrometer after converting urea to nitrogen (1-3). Such methods have the disadvantages of being time-consuming and requiring large sample size. The preparation of sample for ratio mass spectrometric measurement requires tedious operation of a vacuum line; this operation usually takes a couple of days. The amount of urea needed for a ratio mass spectrometric mea-