publicado na web em 26/08/2016A specific LC-MS/MS method was developed and validated for automated determination of codeine in human plasma, using online solid phase extraction (SPE) system coupled with positive ion electrospray ionization tandem mass spectrometry. The method allowed plasma direct injection onto cartridge without sample pre-treatment. Total analysis time per run was 3 min, allowing highthroughput for codeine determination. SPE on-line along a monolithic column (Chromolith Performance RP-18e, 100 mm x 4.6 mm) demonstrated to be highly effective in terms of backpressure, separation speed and peak asymmetry. Calibration curves range was linear 5.0-200 ng mL -1 . Method showed an excellent intra-day and inter-day precision ranged from 2.34 to 7.25% (CV%) as well as great intra-day and inter-day accuracy, ranging from 97.64 to 110% (RE%). SPE-LC-MS/MS method provided selectivity, accuracy, precision, fastness and high-throughput to assess codeine pharmacokinetics in human plasma samples.