Optimization of solid-phase extraction for a liquid chromatographic–tandem mass spectrometric general unknown screening procedure by means of computational techniques

A solid-phase extraction (SPE) method was optimized to suit the particular demands of an information-dependent acquisition LC–MS–MS procedure for general unknown screening in a forensic toxicology setting. In a first phase, a Plackett–Burman screening design with fold-over was carried out to distinguish the significant factors affecting the extraction procedure. This part eventuated in the determination of only three statistically relevant parameters, requiring consecutive optimization. To that end, in phase II of this study, a rotatable central composite design was applied to define the response surface as a function of the significant parameters and to choose the optimal conditions for the SPE.