The method uses an unequal variance t-test at each mass-to-charge ratio in the scan range to determine whether two spectra are statistically associated or discriminated. If the two spectra are associated, a random-match probability is calculated to estimate the likelihood that the mass spectral fragmentation pattern in question occurs by random chance alone. If the two spectra are discriminated, the fragment ions responsible for the discrimination are determined. The current study examined mass spectral data from case samples containing amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), phentermine, and psilocin. All spectra were collected in an accredited forensic laboratory, using routine methods for controlled substance analysis. Using the statistical method, spectra of case samples were statistically associated to the corresponding reference standard at the 99.9-percent confidence level. In these instances, random-match probabilities ranged from 10−39 to 10−29, indicating the probability that the characteristic fragmentation pattern occurred by random chance was extremely small. Further, spectra of case samples were discriminated from other reference standards at the 99.9-percent or 99.0-percent confidence level, with 1-26 ions responsible for discrimination in each comparison. (Publisher abstract modified)