The differentiation of a controlled drug from uncontrolled novel compounds related to regioisomers is a significant issue in forensics. The compound 1-(2,3-dihydro-1H-inden-5-yl)-2-(pyrrolidin-1-yl)butan-1-one (5-PPDI) is a novel synthetic cathinone first identified in 2015 as a new psychoactive substance. 5-PPDI is the indanyl analog of α-PBP, a typical synthetic cathinone, as well as the aliphatic ring analog of MDPBP, a synthetic cathinone with a heterocyclic ring. 5-PPDI can have three possible regioisomers, 1-(2,3-dihydro-1H-inden-1-yl)-2-(pyrrolidin-1-yl)butan-1-one (1-PPDI), 1-(2,3-dihydro-1H-inden-2-yl)-2-(pyrrolidin-1-yl)butan-1-one (2-PPDI), and 1-(2,3-dihydro-1H-inden-4-yl)-2-(pyrrolidin-1-yl)butan-1-one (4-PPDI), differing by the substituted position of the alkyl side-chain. In this study, 5-PPDI and its three regioisomers were synthesized from commercially available precursor compounds and analyzed by gas chromatography/electron ionization–quadrupole mass spectrometry (GC/EI–Q-MS) and by liquid chromatography/electrospray ionization–linear ion trap mass spectrometry (LC/ESI–LIT–MS). The four PPDI isomers could be differentiated by GC/EI–Q-MS with three types of separation columns and by 2nd generation product ion spectra (MS3) analysis using ESI–LIT–MS.