Meconium has become the specimen of choice for determining fetal exposure to drugs of abuse, but its physical complexity can cause interferences from matrix effects. A new method to determine 9-carboxy-11-nor-Δ 9 -THC (9-THCA) and 11-hydroxy-Δ 9 -THC (11-OH-THC) using two-dimensional (2D) GC–MS was developed to reduce interferences and carryover. The method was validated using 70 spiked samples prepared in drug-free meconium and 46 residual patient specimens that were confirmed to contain cannabinoids. Ten patient specimens that failed to confirm due to interferences using the previous GC–MS method were analyzed using the new 2D method and 9-THCA was quantitated in all ten samples. The 2D GC–MS method improved chromatography which significantly reduced interferences and carryover when compared to the previous GC–MS method.