A facile method was developed to quantify unreacted ketene acetals during polymerization of poly(ortho ester)s. The method was based on isotopic (deuterium) labeling of the unreacted ketene acetal groups arising from the diketene acetal monomer, 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5,5]undecane (DETOSU). In deuterium oxide, free ketene acetals are hydrolyzed to an alpha-deuterated ester; ortho ester bonds are hydrolyzed to the nondeuterated analog. The relative abundance of the deuterated ester side chain can be quantified by gas chromatography-mass spectrometry (GC-MS). In the current method, aliquots of a diketene acetal/polyol(s) reaction mixture were dissolved (crosslinked polymers swollen) in methylene chloride and excess D2O. The diketene acetal/polyol(s) reaction mixture was hydrolyzed under mildly acidic conditions to yield pentaerythritol dipropionate (PDP; hydrolysis product of DETOSU). PDP was extracted into an organic phase, silylated, and analyzed by GC-MS. Fragments corresponding to the C2H5C=O + ion (57 a.m.u.) and C2H4DC=O + ion (58 a.m.u.) were monitored and the quantity of free ketene acetal groups were calculated from the peak areas of the chromatograms. The precision of the method was +/- 0.1%. The accuracy, as compared to a parallel H-1-NMR study, was within 5%. This method permits determination of the cure end-point of a poly(ortho ester) polymerization reaction to within +/- 0.25%. The curing kinetics agreed well with DSC branching/crosslinking measurements.