Use of mixed anhydrides for the determination of terfenadine in dosage forms and spiked human plasma

Terfenadine reacts with mixed anhydrides (malonic and acetic anhydrides) pr oducing a yellow-coloured product with intense fluorescence. Based on this fact, a spectrophotometric method was developed for the determination of te rfenadine in dosage forms. The relation between the absorbance at 395 nm an d the concentration is rectilinear over the range 0.5-5 mu g ml(-1) (molar absorptivity is 1.405 x 10(5) l mol(-1) cm(-1)). The reaction product was a lso measured spectrofluorimetrically at 435 nm after excitation at 395 nm. The fluorescence intensity was directly proportional to the concentration o ver the range 0.5-4 ng ml(-1) with minimum detectability (S/N = 2) of 0.07 mu g ml(-1) (similar to 1.5 x 10(-10) M). The different parameters affectin g the development and stability of the reaction product were carefully stud ied and incorporated into the procedure. The proposed spectrophotometric me thod was successfully applied to the dt termination of terfenadine in table ts and suspensions; the percentage recoveries were 99.83 +/- 0.75 and 99.65 +/- 0.83, respectively. The proposed spectrofluorimetric method was applie d to the determination of terfenadine in spiked human plasma. The percentag e recovery was 99.35 +/- 2.19. The method is highly sensitive and specific. No interference was noticed from co-formulated drugs, such as pseudoephedr ine and ibuprofen. (C) 2000 Elsevier Science B.V. All rights reserved.