Gas Chromatography/Mass Spectrometry (GC/MS) testing is used to confirm instant drug test findings. GC/MS can detect the presence of small quantities of a specific drug. Although GC/MS testing is more time-consuming, it provides the most accurate, sensitive, and reliable drug test results. Lab technicians with a high level of expertise are required to perform confirmation testing, so GC/MS is usually reserved for verification of positive immunoassays.

Since GC/MS tests identify drug metabolites and not the parent compound, it can be difficult to discern prescription medication from illicit drugs. This means heroin users will test positive for morphine. All drug testing methods are susceptible to human and environmental error, despite the high accuracy of GC/MS confirmation.