The cannabinomimetic drug JWH-250 is found in herbal “spice” mixtures and is banned in many parts of the world. It is easy to misidentify JWH-250 with the positional isomers JWH-302 and JWH-201 using conventional gas chromatograph/mass spectrometry (GC/MS) because all three compounds have similar GC retention times and nearly identical mass spectra. The isomers differ by the position of a methoxy group on one of the aromatic rings; the methoxy is either ortho, meta or para relative to the indole substituent. Statistical analysis of principal fragment ions in the 70 eV electron ionization mass spectra of each synthetic cannabinoid showed the three isomers to be very significantly different in their respective ratios of m/z 121:91, thus forming an utilizable method for conclusive identification. The different abundance ratios of m/z 121:91 is explained by the ease of loosing the methoxy group when it is ortho, meta or para to an acetyl-indole-containing group in the different isomers. The ratios of m/z 121:91 were averaged across three different instruments over an extended period and provided m/z 121:91 ratios of: JWH-250 (ortho isomer) = 0.4 ± 0.02 (95% CI, N = 14); JWH-302 (meta isomer) = 1.3 ± 0.1(95% CI, N = 6); and JWH-201 (para isomer) = 7.2 ± 0.5 (95% CI, N = 7).