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

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 observed over the concentration range of 0.3–10 μg/ml using polyanion-sensitive electrodes based on tridodecylmethylammonium chloride (TDMAC) as the membrane ion-exchanger. However, optimal quantitative determinations of PPS at μg/ml levels are accomplished via simple potentiometric titrations with polycationic protamine or poly-l-arginine using a membrane electrode formulated with dinonylnapthalene sulfonate (DNNS) as the potentiometric end point detector. Such titrations yield sharp end points and provide consistent mass stoichiometries 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 similar titrations with protamine can be utilized to detect PPS quantitatively in undiluted plasma at concentrations ≥0.5 μg/ml. Fundamental studies regarding the binding of PPS to various polycations can also be accomplished using the TDMA-based polyanion sensor as a detector. Scatchard analysis of the EMF data for the titration of protamine and poly-l-arginine with PPS indicate that both species bind PPS with relatively high affinity (4.4 and 9.4 μM−1, respectively).