LC-MS analysis of selected sulfur-containing non-steroid antiinflammatory agents: Applications to pharmaceutical products

A rapid, specific, sensitive, and reproducible high performance liquid chromatography-mass spectrometric assay has been developed for the quantitation of five sulfur-containing non-steroid anti-inflammatory drugs (NSAIDs), namely, celecoxib (Cel), piroxicam (Per), rofecoxib (Rof), sulindac (Sul), and tenoxicam (Ten), in available tablets and capsules. The examined compounds were extracted from the dosage forms with methanol and chromatographed on a Shim-Pack column using a mobile phase of acetonitrile and 1% acetic acid solution in a ratio 4.1 (Cel, Per, Sul, Ten) or acetonitrile and 20 mM ammonium acetate buffer solution (4:1) (Rof). The analytes were determined by an ion-trap mass spectrometer (Finnigan Mat) using APCI as an ionization process. The eluted compounds were detected either in the positive single ion monitoring mode at m/z 382.0, 332.0, 357.0, 338.4 (Cel, Per, Sul, Ten), or in the negative single ion monitoring mode at m/z 313.2 (Rof). Linear correlations of the peak area and concentration were confirmed for all compounds over the concentration ranges 0.25-1.0 mug/mL (Cel), 0.5-1.5 mug/mL (Per), 0.25-1.0 mug/mL(Sul), 1.0-2.0 mug/mL. (Ten), and 0.1-1.0 mug/mL(Rof). The high specificity of the method was elucidated by analyzing mixtures of piroxicam/tenoxicam and celecoxib/sulindac. The developed method was successfully applied to determine the examined drugs in marketed pharmaceutical products.