Since diabetes mellitus and osteoarthritis are highly prevalent diseases, combinations of\nantidiabetic agents like repaglinide (REP) and non-steroidal anti-inflammatory drugs (NSAID) like\ncelecoxib (CEL) could be commonly used in clinical practice. In this study, a simple and sensitive\nbioanalytical HPLC method combined with fluorescence detector (HPLC-FL) was developed and fully\nvalidated for simultaneous quantification of REP and CEL. A simple protein precipitation procedure\nand reversed C18 column with an isocratic mobile phase (mixture of ACN and pH 6.0 phosphate\nbuffer) were employed for sample preparation and chromatographic separation. The fluorescence\ndetector was set at a single excitation/emission wavelength pair of 240 nm/380 nm. The linearity\n(10â??2000 ng/mL), accuracy, precision, extraction recovery, matrix effect, and stability for this method\nwere validated as per the current FDA guidance. The bioanalytical method was applied to study\npharmacokinetic interactions between REP and CEL in vivo, successfully showing that concurrent\nadministration with oral REP significantly altered the pharmacokinetics of oral CEL. Furthermore, an\nin vitro metabolism and protein binding study using human materials highlighted the possibility of\nmetabolism-based interactions between CEL and REP in clinical settings.
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