Semi-automated 96-well liquid-liquid extraction for quantitation of drugs in biological fluids

A semi-automated liquid-liquid extraction (LLE) technique for biological fl uid sample preparation was introduced for the quantitation of four drugs in rat plasma. All liquid transferring during the sample preparation was auto mated using a Tomtec Quadra 96 Model 320 liquid handling robot, which proce ssed up to 96 samples in parallel. The samples were either in 96-deep-well plate or tube-rack format. One plate of samples can be prepared in approxim ately 1.5 h, and the 96-well plate is directly compatible with the autosamp ler of an LC/MS system. Selection of organic solvents and recoveries are di scussed. Also, precision, relative error, linearity and quantitation of the semi automated LLE method are estimated for four example drugs using LC/MS /MS with a multiple reaction monitoring (MRM) approach. The applicability o f this method and future directions are evaluated. (C) 2000 Elsevier Scienc e B.V. All rights reserved.