Determination of metformin in pharmaceutical preparations using potentiometry, spectrofluorimetry and UV-visible spectrophotometry

New, simple and convenient potentiometric, spectrofluorimetric and spectrophotometric methods are described for the determination of metformin in pharmaceutical preparations. The potentiometric technique is based on preparation of PVC membrane sensors incorporating metformin-reineckate, and metformin-tungstosilicate ion-pairs as electroactive species with dioctylphthalate and o-nitrophenyloctylether as plasticizers, respectively. A membrane consisting of carboxylated PVC plasticized with dibutylsebacate is also prepared and tested. These sensors give rapid Nernstian response for 10(-1)-10(-5) M metformin at pH range 5-11. The metformin-tungstosilicate based sensor is used in a flow-through sandwich cell for flow injection potentiometric determination of metformin. Graphite sensors coated or doped with metformin-tungstosilicate-PVC, Cu-diethyldithiocarbamate and Ni-diethyldithiocarbamate are also prepared and used for monitoring the titration of the drug with tetraphenyl berate (TPB-), Cu2+ and Ni2+ ions, respectively. The spectrofluorimetric method depends on the reaction of metformin with chrysenequinone in alkaline medium to give a Schiff's base, which upon hydrolysis gives the free base. The latter in the presence of l-naphthol gives a fluorescent product with excitation and emission maxima at 450 and 520 nm, respectively. The fluorescence-concentration relationship is linear over the range 20-200 mu g ml(-1) metformin. The proposed spectrophotometric technique involves reaction of metformin with Cu2+ in basic medium to form a Cu-metformin complex. The complex is dissolved in cyclohexylamine and its maximum absorption at 540 nm is measured. Beer's law is obeyed over the range 0.5-2 mg ml(-1) metformin. Various cations, some nitrogenous compounds or drug excipients cause no interferences. Results obtained by these techniques are comparable and compare favorably with data obtained using the British Pharmacopoeia method. (C) 1999 Elsevier Science B.V. All rights reserved.