A study comparing recently available 100 × 3 mm id, 200 × 3 mm id monolithic reversed-phasecolumns with a 50 × 2.1 mm id, 1.8 µm particle packed reversed-phasecolumns was carried out to determine the most efficient approach (using traditional van Deemter analysis and a modern kinetic plot approach) for the rapid screening of samples for 16 illicit drugs and associated metabolites. A plot of column backpressure versusplate number (N) showed a significant advantage of using the monolithic phases, with the 20 cm monolithic column exhibiting a maximum 15 000 plates at a column backpressure of ≈70 bar, compared to ≈7000 plates at 150 bar for the 5 cm 1.8 µm particle packed column. Optimum linear velocities were found to be 0.40 mm s^–1, 0.52 mm s^–1 and 0.98 mm s^–1 for the three above columns, respectively. The 20 cm monolithic column was subsequently applied to the separation and determination of illicit drug contamination on Irish euro banknotes, using methanol extraction followed by LC-MS/MS. Method performance data showed that the new LC-MS/MS method was significantly more sensitive than previous GC-MS/MS based methods for this application, with detection limits in the pg note^–1 region, based upon a 20 µL standard injection. All of the notes examined tested positive for trace quantities of cocaine, with benzoylecgonine detected on 12 of the 45 notes sampled. Traces of heroin were also detected on three of the 45 notes.