Validation of LC–MS-MS Methods for the Determination of Ibuprofen in Miniature Swine Plasma and Synovial Fluid
Published methods for the determination of ibuprofen in biological fluids by liquid chromatography (LC)–UV or LC–mass spectrometry (MS)-MS have quantitation ranges consistent with the relatively high but typical ibuprofen dose (200–800 mg), generally having lower limits of quantitation in the low micrograms-per-milliliter range. For the analysis of plasma and synovial fluid samples from preclinical (miniature swine) studies utilizing a novel ibuprofen dosage form, LC–MS-MS methods were developed and validated over the 10–1000 ng/mL range. Ibuprofen undergoes biotransformation to ibuprofen acyl glucuronide and sublimes under routine bioanalytical sample handling conditions. Procedures were implemented to minimize the impact of these potential liabilities.