Beyond signal maximisation: A multi-response HS-SPME optimisation incorporating minor-compound contribution and GC×GC...

Headspace solid-phase microextraction (HS-SPME) is widely used for volatile profiling, with method development typically guided by responses that reward signal maximisation, such as total area or peak count. On porous adsorptive coatings (e.g., divinylbenzene/Carboxen/polydimethylsiloxane), competitive adsorption complicates this strategy: under aggressive extraction, compounds that are not preferentially adsorbed on the fibre are displaced from the finite number of adsorption sites by more strongly retained volatiles, reducing the contribution of minor compounds observed in the chemical profile. Here, a multi-response Derringer-Suich desirability framework is developed that introduces two responses beyond conventional sensitivity measures: a minor-peak area fraction, serving as an indicator of competitive adsorption, and a two-dimensional separation orthogonality term, capturing how extracted volatiles populate the available separation space. The framework was demonstrated on GC×GC-TOF MS analysis of extra virgin olive oil. A central composite design (extraction temperature, equilibration time, extraction time) was modelled against these two responses alongside three conventional measures: peak count, lipoxygenase-pathway volatile sum, and nonanal area as an oxidation indicator. Across complementary optimisation scenarios, the optimum consistently converged at approximately 46-47 °C, with 25 min equilibration and 60 min extraction. This temperature sits at the lower end of the reported 40-70 °C range, reflecting the suppression of thermally driven oxidation products that increase with extraction temperature. All responses are derived directly from the standard GC×GC peak table, requiring no additional measurement. Together, these responses extend HS-SPME method development beyond signal maximisation, towards volatile profiles that are both representative and well-separated.