[Potentiometric detection of beta-adrenolytic and beta-adrenergic drugs in HPLC systems]

Abstract

This paper presents a comprehensive review of reference literature and the principal results of our own studies on the use of inclusion effects of macrocyclic compounds in the potentiometric detection of hypotensive and antiarrhythmic drugs as well as bronchodilators following their separation in HPLC systems. It was found that the properties of the liquid membrane electrodes embodying some macrocyclic compounds (i.e. trioctylated alpha-cyclodextrin, dibenzo-18-crown-6 or calix[6]arene hexaethylester) enabled reasonable prediction of their sensitivity in terms of the computed hydrophobicity and polarizability parameters of the analyzed drugs. The statistically significant equations enabling the optimalization of the composition of liquid membrane electrodes and the prediction of their detection limits in relation to the molecular structures of cationic drugs were established by applying multiparameter regression procedures. In particular it was indicated that the use of a liquid membrane electrode with trioctylated alpha-cyclodextrin enables sensitive detection (<10(-8) M) of highly hydrophobic drugs (logP >2.5 on the Parham-Hall-Kier scale) such as clenbuterol, bufuralol, and propanolol under HPLC conditions. These results indicate that the developed potentiometric detection method of hypotensive drugs can be considered as a promising alternative to the immunoassay procedures (ELISA) currently recommended for the toxicological determination of trace amounts of the drugs in biological samples. It was also shown that the set of experimentally determined detection limits characterizing the sensitivity of the four different liquid membrane electrodes used in the cation-exchange HPLC system enabled reliable screening and proper pharmacological classification of the beta-adrenergic and beta-adrenolytic drugs analyzed. Using principal component analysis (PCA) of the potentiometric data, it was stated that a differentiation of cardioselective from non-cardioselective beta1-blockers commonly administered as the hypotensive drugs was possible. This result indicates that the new method of potentiometric detection in HPLC systems can be applied as an effective high-throughput screening (HTS) procedure of large combinatorial libraries of newly synthesized drug-like candidates. This may increase the possibilities of identifying the lead compounds to be directed to further specialized biological tests, thus enabling the successful design and formulation of a new generation of more selective and pharmacogenome-oriented hypotensive drugs with reduced side-effects.