Determination of pentosan polysulfate and its binding to polycationic species using polyion-sensitive membrane electrodes

The use of previously developed polyanion and polycation-sensitive membrane electrodes to determine pentosan polysulfate (PPS), an anti-osteoarthritis drug chemically derived from a natural polysaccharide. in buffered saline and biological samples is examined. Owing to PPS's very high anionic charge density, an extremely large non-equilibrium EMF response to PPS is observe d over the concentration range of 0.3-10 mug/ml using polyanion-sensitive e lectrodes based on tridodecylmethylammonium chloride (TDMAC) as the membran e ion-exchanger. However, optimal quantitative determinations of PPS at mug /ml levels are accomplished via simple potentiometric titrations with polyc ationic protamine or poly-L-arginine using a membrane electrode formulated with dinonylnapthalene sulfonate (DNNS) as the potentiometric end point det ector. Such titrations yield sharp end points and provide consistent mass s toichiometries for the complexation between the polycation species and PPS (1.55:1 protamine:PPS; 1.20:1 poly-L-arginine:PPS). It is shown that simila r titrations with protamine can be utilized to detect PPS quantitatively in undiluted plasma at concentrations greater than or equal to0.5 mug/ml. Fun damental studies regarding the binding of PPS to various polycations can al so be accomplished using the TDMA-based polyanion sensor as a detector. Sca tchard analysis of the EMF data for the titration of protamine and poly-L-a rginine with PPS indicate that both species bind PPS with relatively high a ffinity (4.4 and 9.4 muM(-1), respectively). (C) 2001 Elsevier Science B.V. All rights reserved.