Ion-selective electrodes for the H2-receptor antagonists cimetidine and ranitidine

Liquid-membrane and polyvinyl chloride (PVC)-matrix ion-selective electrodes (ISE) that respond to the cationic forms of cimetidine and ranitidine are described. The ion-exchangers were the salts of cimetidine and ranitidine with tetrakis(m-chlorophenyl)borate dissolved in p-nitrocumene or entrapped in PVC polymer in the presence of 2-nitrophenyl octyl ether as plasticizer. The electrodes exhibited a near-Nernstian response in the range 10(-2)-10(-6)M (working pH range 2-7) for ranitidine, and 10(-2)-2 X 10(-5)M (pH 2-6) for cimetidine. Very small PVC-matrix ISE with internal diameters as small as 0.035 inches were constructed and used in combination with small cuvettes, so that measurements could be carried out in 250 muL of stirred solution. The electrodes were applied successfully for the determination of the pKa of the protonated bases and for the determination of the drugs in pharmaceutical preparations. New selective and effective solid-state extraction procedures are described for the extraction of ranitidine from urine and serum samples. Potentiometric methods were developed for the determination of ranitidine in urine and serum samples during a pharmacokinetic experiment.