Oxygen-18 exchange reactions in steroidal ketones. Determination of relative rates of incorporation by gas chromatography-mass spectrometry

Relative rates of O18 incorporation have been measured for the acid catalyzed exchange reaction between H2O18 and steroidal ketones. Microgram samples from a reaction mixture of steroids and H2O18 are injected directly into a gas chromatograph-mass spectrometer. O18-content of each steroid is calculated from the second isotope peak of the molecular ion. Relative rates of incorporation, obtained from pseudofirst-order kinetic plots, varied widely depending on the electronic and steric environment of the carbonyl function. Increasing depolarization of the carbonyl group in ¿4- and ¿1,4-3-ones resulted in exchange rates more than 102 and 104 times slower than the saturated 3-one, while the 16-one group exchanged 8 times more rapidly than the more hindered 17-one. The technique offers a novel means of characterizing steroidal ketones, and represents an example of the considerable utility of mass spectrometry in obtaining kinetic data.