Detection and quantification of non-steroidal anti-inflammatory agents by gas chromatography/mass spectrometry:...

A sensitive and reliable gas chromatography/mass spectrometric assay for diclofenac in plasma using selected ion monitoring is described. The procedure is based on the acidic extraction of diclofenac and ketoprofen (internal standard) with toluene. Both compounds are converted into their ethyl ester derivatives with ethanol containing 0.5% (v/v) sulphuric acid. No internal cyclization to indolone side product is produced in these conditions. The ions monitored are m/z 214 for diclofenac and m/z 209 for ketoprofen. The main recovery of diclofenac added to plasma has been estimated around 84.6% (120 ng ml-1, n = 4). The intra-assay and inter-assay variability were 1.9% and 10.3%, respectively. The sensitivity was lower than 2 ng ml-1. The applicability of the assays to study the bioavailability of two formulations in a multiple-dosage trial is described. The method has been used in more than 600 determinations without any interference.