ION-PAIR SOLID-PHASE EXTRACTION OF CIMETIDINE FROM PLASMA AND SUBSEQUENT ANALYSIS BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

An improved method is described for the solid-phase extraction of cime tidine from plasma or serum with subsequent analysis by HPLC. New aspe cts of the method include protein precipitation with metaphosphoric ac id (5%, w/v), followed by selective adsorption of cimetidine and the i nternal standard ranitidine on the surface of a solid-phase phenyl (PH Bond Elut) column, using octanesulfonate as an ion-pairing agent. Sep aration 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 va riation varied between 0.7 and 4.0%. The procedure provides cleaner an d more stable samples and a better recovery (90 +/- 2.3%) and sensitiv ity (limit of detection 5 ng/ml and limit of quantitation 25 ng/ml) as compared with previous methods.