Abstract: The present invention provides a capability of Ion Mobility Spectrometry/Atmospheric Pressure Ionization Mass Spectrometry (IMS/MS) in the negative ion mode for Ozone detection and methods for ozone layer depletion monitoring in laboratory environment. Ammonium hydroxide vapors, as a dopant chemical, introduced to the inlet system of the IMS/MS interfaced with the reaction sphere enables ozone ionized to be O3?. The data obtainable from proposed methods show how ozone is depleted and which compound affect the most for O3 destruction among the O3 depletion substances of Chloro Fluoro Carbons (CFCs), Hydro Fluoro Carbons (HFCs), Hydro Chloro Fluoro Carbons (HCFCs), Hydro Chloro Bromo Carbons (HCBCs), and Hydro Chloro lodo Carbons (HClCs). Based on the results obtainable, more likely the IMS alone system without coupling with the mass spectrometer (IMS/MS) will rather be selected to develop as a spatial real time ozone layer depletion monitor.