Green and sustainable drug analysis: Combining microsampling and microextraction of drugs of abuse

A novel method combining microsampling of whole blood containing drugs of abuse with 96-well liquid solution microextraction (Parallel Artificial Liquid Membrane Extraction, PALME) and analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was evaluated. Different donor solutions, supported liquid membranes and acceptor solutions were tested, and the most promising set-up was validated. The method included common classes of drugs of abuse, such as opioids, amphetamines, cocaine, benzodiazepines and z-hypnotics. Extraction recoveries above 70% were found for 13 of the compounds, while the last four compounds had recoveries of 10–58%. THC was not extracted with the current method. A linear calibration model was found for all drugs but morphine. Limits of quantitation were between 1 and 5 ng/mL and inter-day precision and accuracy was within 20% for all compounds except for morphine and zopiclone that had a CV of 25% at LOQ. All matrix effects were within 78–123%. Samples were stable for 14 days except for zopiclone and zolpidem. With low-cost, high sample throughput, semi-automated miniaturized sample preparation in combination with dried blood microsamples, and an Eco-Scale score of 78, the proposed method fulfills green chemistry principles.