Variation in SPE sample preparation techniques can significantly affect analyte recovery, reproducibility, and overall quality. The studies highlighted here clearly show that even very common and simple operator mistakes can severely compromise the quality of results. Training and experience can help to mitigate these problems, though time and resources may not always be available. Fully automated SPE instruments also provide a solution yet are complicated and costly to set-up and run. By employing the semi-automated Otto SPEcialist Positive Pressure Manifold, with its easy-to-use, compliant software and programmable pressure profiles, reproducible, high-quality results can be obtained regardless of user expertise and without significant capital investment.