Parallel artificial liquid membrane extraction: micro-scale liquid-liquid-liquid extraction in the 96-well format

Background: This paper reports development of a new approach towards analytical liquid-liquid-liquid membrane extraction termed parallel artificial liquid membrane extraction. A donor plate and acceptor plate create a sandwich, in which each sample (human plasma) and acceptor solution is separated by an artificial liquid membrane. Parallel artificial liquid membrane extraction is a modification of hollow-fiber liquid-phase microextraction, where the hollow fibers are replaced by flat membranes in a 96-well plate format. Results: Four basic drugs (pethidine, nortriptyline, methadone and haloperidol) were extracted from human plasma in 30 min, followed by analysis with LC-MS/MS. Extraction recoveries for the model analytes were in the range of 34-74% from human plasma. LOQs were in the range of 0.01-0.35 ng/ml, linearity above 0.9955 for all drugs and with RSD values below 12%. Conclusion: Liquid-liquid-liquid membrane extraction was successfully performed in a slightly modified commercially available 96-well plate format.