Simultaneous determination of paracetamol and chlorpheniramine in human plasma by liquid chromatography-tandem mass spectrometry

An analytical method for the determination of paracetamol and chlorpheniram ine in human plasma has been developed, validated and applied to the analys is of samples from a phase I clinical trial. The analytical method consists in the extraction of paracetamol and chlorpheniramine with diethyl ether, followed by the determination of both drugs by an LC-MS-MS method, using 2- acetamidophenol as internal standard. The intra-assay and inter-assay preci sion and accuracy of this technique were good and the limit of quantitation was 0.5 mu g/ml of plasma for paracetamol and 0.2 ng/ml for chlorphenirami ne. The concentration working range was established between 0.5 mu g/ml and 25 mu g/ml for paracetamol and between 0.2 ng/ml and 50 ng/ml for chlorphe niramine. This method has been used for analyzing more than 1200 human plas ma samples from a clinical study with 24 volunteers. (C) 2000 Elsevier Scie nce B.V. All rights reserved.