An investigation of the utility of QuEChERS for extracting acid, base, neutral and amphiphilic species from example environmental and clinical matrices.

Accurate measurement of the composition of complex samples is key for the safety and efficacy of a range of products used in daily life, with sample preparation a critical step in this workflow. QuEChERS is one such method, however published protocols do not explicitly address acidic, basic, neutral, and amphiphilic species in a single protocol and often use extra steps or an alternative preparation to recover the breadth of chemical types. Our work addresses this need by investigating the use of QuEChERS for monitoring this wide range of chemistries within environmental solids and blood plasma, using a protocol that can accommodate both milliliter and microliter sample volumes. While published methods can require significant resource and time, our approach offers a reduction in preparation time (for environmental samples), with the "micro-QuEChERS" protocol offering a further reduction in cost. The analytical performance of these methods were assessed using reversed-phase LC-MS and showed good accuracy, precision, and sensitivity for the expected concentrations in the tested applications. Target analytes of variable lipophilicity/acidity were extracted and isolated from soil, with largely repeatable matrix effects < 15%RSD and recoveries of 39-100%. An initial "proof-of-concept" investigation using the "micro-QuEChERS" protocol showed reduced matrix enhancement (median value of 90%ME) for soil, and improved matrix effects and recovery (>65%) for blood plasma. This novel sample preparation method can therefore offer an improved approach with wider applicability providing "cleaner" extracts than other methods used for high-throughput clinical analysis.