Use of stable isotopes to determine compliance

The natural variation in the abundance of stable isotopes of light elements (C, H, O, N) in humans is less than 0.5%. Much larger variations can be induced through administration of drugs labeled with enriched isotopes of these elements. Such labels thus can be used as tracers of compliance. Variations of several percent can be generated without adverse physiological effect. An example is presented of the use of deuterium oxide as a tracer, and a scheme of sampling moisture in expired air is proposed, in which the subject can easily collect a sample and present it for rapid analysis. Tracer levels can be used to estimate the degree of compliance. The labeled compound can be selected to match the drug being tested with respect to residence time in the body. Except for deuterium, the cost of such stable isotope tracers is at present prohibitive. The main problem with the use of stable isotopes in compliance studies is the cost of the tracer, a biologically acceptable substance labeled with a rare-stable isotope. Our original experiments were carried out using 13C-glucose, which costs at present about $600/g. To carry out a tracer experiment on an individual, approximately 10 mg of uniformly labeled tracer would be administered, which would result in a 5% shift of the 13C/12C ratio, which is easily detectable. To minimize the cost of such a study, we proposed utilizing the cheapest enriched light isotope that is available, namely, deuterium. Using a ratio-detecting mass spectrometer in which a sample is compared with a standard, it is possible to detect enrichment or depletion of deuterium with respect to 1H at the level of 0.1%.(ABSTRACT TRUNCATED AT 250 WORDS)