Determination of diclofenac sodium, flufenamic acid, indomethacin and ketoprofen by LC-APCI-MS

A sensitive, selective and accurate high-performance liquid chromatography-mass spectrometry (LC-MS) assay for the determination of selected non-steroidal anti-inflammatory drugs (NSAIDs), namely diclofenac sodium (DIC), flufenamic acid (FLU), indomethacin (IND) and ketoprofen (KET), either individually or in mixtures, was developed. The examined drugs were injected onto Shim-pack GLC-CN column and were eluted with a mobile phase consisting of acetonitrile and 20 mM ammonium acetate solution (5:1 v/v)/pH 7.4 at a flow rate 1 ml min−1. The mass spectrometer, operated in the single ion monitoring mode, was programmed to admit the negative ions [M–H]− at m/z 295.9 (DIC), 280.1 (FLU), 355.8 (IND) and 252.9 (KET), respectively. The calibration curves were linear (r≥0.9993) over the concentration range 50–300 ng ml−1 (FLU, DIC) and 100–500 ng ml−1 (KET, IND) with detection limits of 0.5–4.0 ng. The mean predicted concentrations for the analytes were in the range −5.9 and 5.2% of the nominal concentrations. Within-day and between-day precision were in the range of 0.8–9.1% of the R.S.D. Mean recovery percentages of the individual compounds from laboratory-made mixtures and pharmaceutical formulations were (99.5–101.5%) and (100.6–102.2%), respectively.