Thermodynamic dissociation constants of isocaine, physostigmine and pilocarpine by regression analysis of potentiometric data.
Concentration and mixed dissociation constant(s) of three drug acids, H(J)L, isocaine, physostigmine and pilocarpine, at various ionic strengths, I, in the range 0.03-0.81 and 25 degrees C have been determined with the use of regression analysis of potentiometric titration data when common parameter, pK(a), and group parameters E'(0), L(0), and H(T) are simultaneously refined. Internal calibration of the glass electrode cell in the concentration scale [H(+)] performed during titration was used. The estimate of ill-conditioned group parameters has a great influence on a systematic error in estimated pK(a) and therefore it makes the computational strategy important. As more group parameters are refined and a better fit achieved, a more reliable estimate of dissociation constants results. The thermodynamic dissociation constant, pK(a)(T), an ill-conditioned ion-size parameter, å, and the salting-out coefficient, C, were estimated by non-linear regression of {pK(a), I} data and an extended Debye-Hückel equation. The goodness-of-fit test based on regression diagnostics is a measure of the reliability of parameters, and proves that reliable estimates for isocaine pK(a)(T)(=)8.96(1), å=8(3) A and C=0.50(3) at 25 degrees C, for physostigmine pK(a)(T)(=)8.07(3), å=19(26) A and C=0.64(3) at 25 degrees C, and for pilocarpine pK(a)(T)(=)7.00(1), å=7(1) A and C=0.53(2) at 25 degrees C were found.
Meloun
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Department of Analytical Chemistry, University of Pardubice, 532 10 Pardubice, Czech Republic.
Cernohorský
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