HIGH-THROUGHPUT SOLID-PHASE EXTRACTION FOR THE DETERMINATION OF CIMETIDINE IN HUMAN PLASMA

For the implementation and validation of an automated 'high-throughput ' solid-phase extraction (SPE) system, using microtiter solid-phase te chnology and a pipetting robot, a SPE method previously validated manu ally for cimetidine in human plasma was adapted. Sample cleanup was pe rformed by means of SPE using Microlute extraction plates in the 96-we ll format, each well filled with 50 mg of Varian C-18 sorbent. Separat ion was performed by reversed-phase high-performance liquid chromatogr aphy (HPLC) with UV detection at 234 nm. The validated calibration ran ge was from 0.100 to 5.00 mg/l, with an inaccuracy and imprecision bel ow 20% at all concentration levels. Validation results on linearity, s pecificity, precision, accuracy and stability are shown and are found to be adequate. Cross-check analysis of samples from a clinical trial showed that there is a good correlation between results obtained by th e automated method and results obtained by the manual method. The aver age sample preparation time for a technician decreased from approximat ely 4 min per sample to 0.6 min. A sample throughput of at least 160 s amples per day can be achieved, the HPLC analysis time being the rate- limiting step. (C) 1998 Elsevier Science B.V. All rights reserved.