Occupational exposures to isocyanates can lead to occupational asthma. Once sensitized, some workers could react to isocyanate monomers at concentrations below 1% of the Permissible Exposure Limit of 5 ppb in air. Currently available methods are not sufficiently sensitive to adequately evaluate isocyanates present at these levels in workplace air. This article describes a novel method for isocyanate determination allowing the ultratrace quantification in workplace air of hexamethylene diisocyanate, 2,4-toluene diisocyanate and 2,6-toluene diisocyanate monomers. Sampling is performed during a complete workshift at a flow rate of 1 L min⁻¹ with a cassette containing a 1-(2-methoxyphenyl)piperazine-impregnated 25 mm filter. Analysis is performed using liquid chromatography hyphenated with coordination ionspray tandem mass spectrometry. The analytical method’s linearity was measured for a concentration range varying from the limit of detection of 0.04–0.13 ng mL⁻¹, depending on the monomer, up to approximately 32 ng mL⁻¹ for every isocyanate monomer, all with correlation coefficients (R²) greater than 0.999. The analytical method’s lower limit of quantification combined with an adapted sampling strategy allow the quantification of isocyanate monomers down to 0.04 ppt for an 8 h work shift when a lithium adduct is used, which is more than 300 times lower than the most sensitive method currently available. This novel method can be used to confirm the very low level of isocyanate monomers for the safe reassignment of sensitized workers and it is also useful for charting the isocyanate dispersion tail in workplace environments.