Stable isotope labeling (SIL) still has not been used very much in pediatric and perinatal clinical pharmacology. However, this method has numerous advantages. It allows one to determine the concentration of drugs with great sensitivity, thereby allowing quantification in small amounts of biologic samples. It also allows quantification with great specificity, eliminating interference by drug metabolites found in some radioactive tracer methods. SIL is safe because stable isotopes are not radioactive. The only possible toxicity that may be related to an isotope effect is a slowing of biochemical reactions because of the greater mass of the stable isotope. Because of the great difference between deuterium and hydrogen, a significant isotope effect occurs only with deuterium. However, toxicity related to the isotope effect of deuterium can only be produced by very high levels of deuteration (>15% of body water), far higher than the amount of deuterium in a typical tracer dose of drug.1 SIL also allows noninvasive in vivo studies such as the co2 breath test (CBT). All of these advantages explain the great potential interest in SIL in pediatric pharmacology. The costs of stable isotopes and limited facilities available for sample analysis are undoubtedly the greatest limitations to their increased use. SIL is useful in different types of studies,2 such as studies on the fate of drugs (drug metabolic pathways and pharmacokinetics), determination of compliance, and assessment of therapeutic and unwanted effects of drugs. The use of SIL of drugs in positron emission tomography investigations is not addressed in this article. ### Definition In the periodic table, the elements are ranked according to their atomic number, ie, the number of protons contained in the nucleus. All elements located at the same place in the table are isotopes of the same family, for example, the family of carbon. All members …