Macrocycle versus podant-type neutral ionophore in potentiometric detection of mucolytic agents following separation by various HPLC modes

Potentiometric detection of lipophilic drugs such as clenbuterol, ambroxol and bromhexine in standard-bore cyano and narrow-bore hybrid, reversed-phase HPLC systems was developed to enable specific determination of these mucolytic agents in some marketed oral-formulations. The macrocycle and podant-type, neutral ionophores, respectively: hexakis(2,3,6-tri-O-octyl)-alpha-cycloclextrin (CDX) and NNN',N'-tetracyclohexyl-oxybis(o-phenyleneoxy)diacetamide (TOPA), were used to construct PVC-based, liquid membrane electrodes. In acidic aqueous-acetonitrile, mobile phases both ionophores improved the sensitivity of these electrodes for mucolytic agents when compared to single-wavelength UV detection - as well as with the ionophore-free based electrode. in the case of bromhexine, indicating highest lipophilicity (IogP 6.40), detection limits of 2.6 x 10(-10) and 1.4 x 10(-10) M (injected concentration) were achieved with a signal-to-noise (SIN) ratio of 3 with the TORA-modified, liquid membrane electrode in the various RP-HPLC systems. The results of procedures validated for simultaneous potentiometric determination of clenbuterol and ambroxol in tablets marketed in different countries are also presented.