Abstract: An ISE for diflunisal (I) of the PVC membrane-type was constructed by trapping the 0.01 M tetraheptylammonium-I liquid ion exchanger in 2-nitrophenyl octyl ether solution in a PVC matrix by the method of Craggs et al. (J. Chem. Educ., 1974, 51, 541). The electroactive membrane (diameter 6 mm) was attached to a commercially available nitrate electrode, placed in a potentiometric flow-through cell with Ag/AgCl (4 M KCl) as reference electrode and transferred to the flow injection analyzer.. Portions (85 µL) of sample in 10 mM NaOH were injected into a carrier stream of 10 mM NaOH (2.6 ml/min), mixed with a flow of 0.05 M Tris buffer of pH 8 (1.4 ml/min) in a 50 cm mixing coil and detected by the potentiometric ISE. The electrode exhibited a Nernstian response over the range 0.1-5 mM I and the detection limit was 0.026 mM. The RSD (n = 10) was 0.38% at 1 mM I. Under optimized conditions, the operative life of the ISE was 3 months. A diflunisal ion selective electrode of the PVC membrane type with an ion-exchanger consisting of the tetraheptylammonium-diflunisal ion pair is described. The sensor exhibits a rapid, near-Nernstian, selective response to diflunisal anion in the pH range 7-10, with a (batch) detection limit of 1 x 10^-5 M. The ion sensor was used as a flow detector in an automated flow injection analyzer to develop routine methods for assays (concentration range 1-50 x 10^-4 M, (flow) detection limit 2.6 x 10^-5 M), content uniformity, and dissolution studies of diflunisal formulations. No serious interference from common ions and tablet excipients was found, and the drug can be directly determined in colored samples without separation steps. Fourty measurements can be performed automatically per hour with a precision of 0.5-1.8% relative standard deviation. The automated method for the dissolution test provides a complete dissolution profile by the end of the experiment. Using the constructed ion sensor, the intramolecular hydrogen bonding of the diflunisal anion was studied, thereby revealing a new application of ion sensor potentiometry.

Abstract: In the illustrated liquid-liquid extraction flow injection system, a stream of diflunisal (I) standard solution (0.8 mL/min) was merged with an air-segmented flow of Britton-Robinson buffer of pH 11 (0.56 mL/min) in a glass coil (35 cm x 1 mm i.d.). The merged solution was mixed with aqueous 0.5 mM methylene blue in a glass coil (35 cm x 1 mm i.d.). This solution was extracted with a stream of CHCl3 (0.7 mL/min) in a glass coil (100 cm x 1 mm i.d.) and the organic phase was separated and simultaneously deaerated prior to detection at 650 nm. Under optimum conditions, the calibration graph was linear from 0.025-5 µg/mL of I. RSD (n = 5) were 0.3-12.4% over the calibration range. The method was used to the analysis of I in ethanolic extracts of tablets. Results agreed with those of a control UV method.