Miniaturized Membrane Sensors for Potentiometric Determination of Metoprolol Tartrate and Hydrochlorothiazide

Four microsized graphite and platinum wire poly(vinyl chloride) matrix membrane electrodes responsive to some drugs affecting cardiovascular system, Metoprolol tartrate (MT) and Hydrochlorothiazide (HZ) were developed, described and characterized. These sensors were constructed by using (2-Hydroxypropyl)-beta-cyclodextrin (2HP beta-CD) as an ionophore which has a significant influence on increasing both membrane sensitivity and selectivity. The four sensors were fabricated in a polymeric matrix of carboxylated polyvinyl chloride (PVC-COOH) and dioctylphthalate (DOP) as a plasticizer, based on the interaction between the drugs and the dissociated COOH groups in the PVC-COOH. Fast and stable Nernstian responses of 1.0 x 10(-6)-1.0 x 10(-2) M for MT (sensors 1 and 2) and of 1.0 x 10(-7)-1.0 x 10(-3) M for HZ (sensors 3 and 4) over pH range 3.0-9.0 and 3.0-7.0 for the MT and HZ sensors respectively were obtained. Nernstian slopes of 56.2, 54.6, 19.0 and 20.8 mV/decade for electrodes 1-4 respectively were observed. The proposed method displayed useful analytical characteristics for the determination of MT and HZ in their pure powder forms with average recoveries of 99.11 +/- 0.357, 99.21 +/- 0.389, 100.08 +/- 0.459 and 100.28 +/- 0.438% for sensors 1-4 respectively. The lower limit of detection (LOD) were 5.5 x 10(-6), 4.5 x 10-6, 4.8 x 10(-8) and 5.0 x 10-8 M for sensors 1-4 respectively indicated high sensitivity. The four sensors displayed a good stability over a period of 6 weeks. The selectivity coefficients of the developed sensors indicated excellent selectivity. Results obtained by the four electrodes revealed the performance characteristics of these electrodes which evaluated according to IUPAC recommendations. The method was successively applied for the determination of MT and HZ in presence of each other, in presence of Salamide (SA), the main degradation product of HZ, in their pharmaceutical formulations and in human plasma samples. Statistical comparison between the results obtained by this method and those obtained by the official methods of the drugs was done and no significant difference was found.