The assay of acetaminophen (APAP) and ascorbic acid (AA) was performed by liquid chromatography (LC) with amperometric detection at a screen printed carbon based electrode poised at +0.6 V versus Ag pseudoreference electrode. A microparticle based conventional RP-C18 and a monolithic RP-C18 column were studied comparatively for the analytes separation using a mobile phase based on 0. 1 M phosphate buffer-methanol 91: 9 (v/v) at pH 6.5. The linear calibration range for both compounds was comprised within 2 x 10(-7)-1 x 10(-4) M. Limit of detection (LOD) for APAP and AA was 2 x 10(-7) and 5 x 10(-7) M, respectively and the limit of quantification (LOQ) was 5. 10(-7)and 1 x 10(-6) M, respectively. Square wave voltammetry at a Nafion modified glassy carbon electrode was developed and applied to the determination of APAP in order to validate the results obtained by the monolithic LC method for drug formulations.