Two new techniques for analyzing praziquantel (PZQ), an effective antiparasitic drug used in fresh and saltwater aquariums, were optimized and compared. One method was based on voltammetry and the other method used gas chromatography combined with mass spectrometry (GC-MS), although both procedures utilized the same sample pretreatment strategy which involved the PZQ being quantitatively transferred into acetonitrile using solid phase extraction. GC-MS analysis led to lower limits of detection (0.32 μM, 0.10 ppm) and quantification (0.72 μM, 0.22 ppm) compared to voltammetry, although both methods gave acceptable quantification for levels of PZQ > 25 μM (7.8 ppm). GC-MS is preferred for the most accurate determination, but voltammetry may provide a cost-effective alternative for detecting PZQ where on site testing is required.