APPLICATION OF A STANDARDIZED COEXTRACTIVE CLEANUP PROCEDURE TO ROUTINE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY ASSAYS OF TEICOPLANIN AND GANCICLOVIR IN PLASMA

Deproteinization of plasma samples with acetonitrile followed by coext racting acetonitrile and lipophilic solutes with chloroform, as alread y proposed for methotrexate, is stressed as a general sample cleanup p rocedure for liquid chromatography of highly polar drugs, and was vali dated for two more applications: teicoplanin and ganciclovir. A dedica ted ''prevalidation'' experimental design was used to assess performan ces of both assays, including sample preparation. Deviations from line arity were less than 10% over the ranges of 3.1 to 50 mg/l (teicoplani n) and 0.2 to 15 mg/l (ganciclovir), respectively, and limits of quant itation were 0.09 and 0.01 mg/l, respectively. Mean chromatographic me asurement R.S.D.s were 4.6% and 1.9%, respectively, with an additional mean cleanup R.S.D. of 2% for both. Mean analyte losses ascribable to cleanup were 6% and 2.5%, respectively from water, and 18% and 12%, r espectively from the plasma matrix. (C) 1998 Elsevier Science B.V.