Exhaustive electromembrane extraction of some basic drugs from human plasma followed by liquid chromatography–mass spectrometry

Citalopram, loperamide, methadone, paroxetine, pethidine, and sertraline were extracted exhaustively with electromembrane extraction (EME) by increasing the number of hollow fibers from one to three. Experiments reported recoveries in the range 97–115% from 1000 μl spiked water samples. EME was accomplished with 200 V as extraction voltage, the extraction time was set to 10 min (equilibrium), and the extraction unit was subjected to 1200 revolutions per minute (rpm). The same experiment with different geometry in a stagnant system conducted with 21 μl acceptor solution provided recoveries from 50 μl undiluted human plasma (pH 7.4) in the range of 56–102% for the six basic model substances. In each experiment the acceptor solution was distributed into three separately hollow fibers in the same sample vial. The importance of an electrical field was verified by comparing EME with liquid-phase microextraction (LPME) under optimal conditions and demonstrated that the time needed to reach equilibrium was reduced by EME. EME–LC/MS provided linearity >0.99 (r2 values) for the six basic model substances, and the repeatability within the low therapeutic range (10 ng/ml) was in the range 5.1–21.4% RSD. LC–MS provided estimated limit of quantification (S/N = 10) in the range 0.6–3.2 ng/ml. Eventually, patient samples from a reference laboratory were analyzed and provided reliable results with a relative difference <14% compared to stated values from the reference laboratory.