Ion-pair solid-phase extraction of cimetidine from plasma and subsequent analysis by high-performance liquid...

An improved method is described for the solid-phase extraction of cimetidine from plasma or serum with subsequent analysis by HPLC. New aspects of the method include protein precipitation with metaphosphoric acid (5%, w/v), followed by selective adsorption of cimetidine and the internal standard ranitidine on the surface of a solid-phase phenyl (PH Bond Elut) column, using octanesulfonate as an ion-pairing agent. Separation was achieved on a LiChrosorb RP-18 column with a mobile phase consisting of acetonitrile-0.01 M phosphate buffer pH 3.0 containing 0.005 M octanesulfonate (22:78, v/v). The intra-assay coefficient of variation varied between 0.7 and 4.0%. The procedure provides cleaner and more stable samples and a better recovery (90 +/- 2.3%) and sensitivity (limit of detection 5 ng/ml and limit of quantitation 25 ng/ml) as compared with previous methods.