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The detection and identification of phosphodiesterase type 5 enzyme (PDE-5) inhibitors in dietary supplements poses an analytical challenge due to the large number of analogs and isomers currently available and the continued introduction of novel analogs. Trapped ion mobility spectrometry (TIMS) in conjunction with liquid chromatography (LC) and electrospray ionization tandem mass spectrometry (MS/MS) can be used for the analysis of two groups of isomeric PDE-5 inhibitor analogs.