Methylcellulose-immobilized reversed-phase precolumn for direct analysis of drugs in plasma by HPLC

We evaluated a new restricted access media (RAM) precolumn for direct analy sis of drugs in plasma using a column switching HPLC system. The new RAM ma terial was prepared by the modification of the external surface of porous s ilica with hydrophilic methylcellulose (MC), followed by modification of th e internal surface with octadecylsilane (ODS). The external surface of the MC-immobilized ODS silica material (MC-ODS) suppressed the adsorption of pr oteins, while the internal surface of MC-ODS retained various types of drug s, such as ketoprofen, propranolol, caffeine and atenolol in plasma samples . In addition, MC-ODS allowed direct analysis of drugs in a 1000- muL plasm a sample to monitor trace amounts of analytes contained. Reduced efficiency and clogging of the MC-ODS precolumn and/or the analytical column were not observed even after the repetitive injection of plasma sample up to 40 mL. Our results indicated that the MC-ODS precolumn could be used in pharmacod ynamic and clinical studies.