Toward Sustainable Clinical Analysis: Benchmarking Plastic Use in LC–MS Sample Preparation – Exemplified by Ketamine Analogs in Whole Blood

The aim of this study was to assess and benchmark plastic consumption in sample preparation for forensic analysis, alongside the development of an LC–MS method for ketamine analogs in whole blood, with various sustainability-related scores and parameters examined throughout. Ketamine analogs are emerging psychoactive substances associated with intoxication and fatalities globally. An analytical method was developed for determining ketamine and eight of its analogs (DCK, DMXE, 2-FDCK, 3-MeO-PCE, MXE, MXiPr, MXPr, O-PCE) in human whole blood. Focus was placed on traditional analytical parameters, but also the consumption of plastics and reagents, an overlooked aspect of clinical and forensic chemistry. We evaluated three sample preparation techniques: protein precipitation (PPT), liquid-liquid extraction (LLE), and electromembrane extraction (EME). While PPT and LLE are well-established techniques used in clinical settings, EME (i.e. electrophoresis across an oil membrane) is a less established but highly promising approach. All three sample preparation approaches demonstrated similar performance, with recoveries above 85% and matrix effects averaging approximately 100%. The EME approach was subsequently refined using a Box-Behnken-based design of experiment, and the method was validated according to the American Academy of Forensic Sciences guidelines. All validated parameters were within the limits, suggesting that the tunable EME approach is a potentially valuable tool in clinical chemistry. The amount of plastic consumables per 100 samples was calculated as being 511 g for PPT, 864 g for LLE, and 303 g for EME. Correspondingly, the amount of organic solvent consumption per sample was 470 µL, 1570 µL, and 210 µL. The AGREEprep scores (ranges from 0 to 1, 1 is best) were 0.48 ± 0.04, 0.36 ± 0.04, and 0.55 ± 0.05. EME fared best in greenness. However, the investigated approaches have a significant use of single-use consumables, inviting for sample preparation approaches that can reduce the plastic footprint toward more sustainable clinical chemistry. The rounded value of PPT (arguably the most used approach for related samples) is 0.5 kg per 100 samples, and we propose this number be used as a benchmark for plastic consumption in today´s sample preparation. This may serve as a practical reference point when developing and evaluating future sample preparation strategies.