Analytical procedures for the determination of meperidine, tramadol and oxycodone in oral fluid have been developed and validated using gas chromatography-mass spectrometry (GC/MS) following initial screening with enzyme linked immunosorbent assay (ELISA). The oral fluid samples were collected using the Quantisal device, and any drugs present were quantified using mixed mode solid-phase extraction and electron impact GC/MS. For confirmation, three ions were monitored and two ion ratios determined, which were within 20% of those of the known calibration standards. The limits of quantitation were 10 ng/mL; the intra-day precision of the assays (n=5) was 2.33%, 1.00% and 7.61%; inter-day precision 2.48%, 2.44% and 5.8% (n=10) for meperidine, tramadol and oxycodone, respectively. The percentage recovery of the drugs from the collection pads was 86.7%, 87.7% and 96.6%, respectively (n=6). The methods were applied to specimens obtained during research studies in the USA.