An improved HPLC method overcoming Beer's law deviations arising from supramolecular interactions in tolfenamic acid and cyclodextrins complexes

Inclusion complexes of tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, with methyl-beta cyclodextrin and hydroxypropyl-beta cyclodextrin were prepared and characterised. Spectrophotometric, chromatographic (RP-HPLC) and H-1 NMR studies of the complexes were conducted. It was observed that cyclodextrins influence TA's molar absorptivity leading to Beer's law deviation. Consequently, the accuracy problem arose, urged for the application of specific chromatographic conditions for the determination of TA in the presence of CDs. A new HPLC method was developed and validated. TA was analysed on a C18 column 5 mu m (150 x 4.6 mm), using a column thermostat regulated at 30 degrees C. The mobile phase consisted of methanol-phosphate buffer solution (pH 3.2; 0.07 M) (90:10 v/v) and the flow rate was set at 2.0 mi min(-1). The detector was operated at 286 nm. TA was successfully determined, overcoming the problems arising from the presence of cyclodextrins. (C) 1998 Elsevier Science B.V. All rights reserved.