Green in-Line Ion Selective Electrode Potentiometric Method for Determination of Amantadine in Dissolution Media and in Pharmaceutical Formulations

Amantadine HCl (AMN) is a well-known antiviral agent. Chemically, AMN chromophore privation leads to the absence of UV-absorbance, a condition that hinders direct spectrophotometric or simple chromatographic determination using common detectors without prior derivatization steps. In this work, an environmentally friendly ion selective electrode (ISE) method was developed for the determination of AMN, and measurements were carried out directly in the aqueous solution of the sample without pretreatment or derivatization steps. PVC-membranes were fabricated using nitrophenyl octyl ether as a plasticizer along with different cation exchangers, responses were compared, and that containing phosphomolybdic acid proved to have the best near-Nernstian slope through a wide linear range (4.57 x 10(-7)) (1.0 x 10(-2)) M. The ion pair was obtained by soaking the membrane sensor in a 1 x 10(-2) M solution of AMN. The sensor was able to determine AMN in colored and turbid solutions of its tablets and capsules without prior extraction, pretreatment, filtration, or derivatization steps. Additionally, the sensor was successfully applied as a benchtop real-time inline analyzer in dissolution monitoring experiments from its capsules and tablets formulations as per the recommended USP and FDA regulations, respectively, where no sample withdrawal, pretreatment, or filtration was required. Sensor response was validated as per IUPAC recommendations. The proposed technique provided a green eco-friendly method that saves cost, time, and effort and consumes the least amount of chemicals.