SummaryPotentiometrTc detection of lipophTlic 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 formula tions. The macrocycle and podant type, neutral ionophores, respectively: hexaks(2,3,64ri O octyl) ~ cyclodextrin (CDX) and N,N,N',N'4etracyclohexyl oxybis(o phenyleneoxy)diaceta mide flOPA), were used to construct PVC based, liquid membrane electrodes. In addic aqu eous-acetonTtrile, mobTle phases both Tonophores Tmproved the sensitTvTty of these electrodes for mucolytic agents when compared to single-wavelength UV detedTon -as well as wTth the ionophore-free based electrode. In the case of bromhexTne, TndTcating highest ITpophilTdty (IogP6.40), detection limits of 2.6 x ]0 lo and 1.4 x ]0 l~ (injected concentration) were achieved with a signal-to-noTse (S/N) ratio of 3 wTth the TOPA-modified, liquid membrane electrode in the varTous RP-HPLC systems. The results of procedures validated for sTmultaneous potentiometrTc determination of clenbuterol and ambroxol Tn tablets marketed in di[ferent countries are also presented.