A facile preparative method for stable isotope labeled molecules is widely demanded in analytical standard chemicals, biochemical science and medical applications. A rapid O-16-O-18 isotope exchange reaction of carbonyl group to attain a high isotopic purity has been demonstrated using a capillary column reactor packed with Dowex 50WX4 resin as a solid acid catalyst. Thus, carbonyl-O-18 compounds such as benzaldehyde-O-18, 3-/4-nitrobenzaldehydes-O-18, 1-naphthaldehyde-O-18 and acetophenone-O-18 were produced with more than 95 at.% purity under the stable flow operation at a moderate temperature within a residence time of 51 s. when the acetonitrile solutions of carbonyl-O-16 compounds were injected to the reactor with 100 eq. mol of (H2O)-O-18. The maximal product isotopic ratio, z(max), has been formularized as z(max) = (x(0y) + z(0))/(y + 1), where x(0) and z(0) are isotopic ratio of H2O and carbonyl group as reactants, respectively, and y is the molar ratio [[H2O]/[carbonyl group]. The achievement ratio of the actual isotopic ratio (z) to theoretical z(max) has reached 0.98 or higher. (C) 2010 Elsevier B.V. All rights reserved.