title: Simultaneous high-throughput determination of clenbuterol, ambroxol and bromhexine in pharmaceutical formulations by HPLC with potentiometric detection.
abstract: Potentiometric detection of clenbuterol, ambroxol and bromhexine in marketed pharmaceuticals was described in six isocratic HPLC systems. The podant- and macrocyclic-type neutral ionophores, N,N,N',N'-tetracyclohexyl-oxybis(o-phenyleneoxy)diacetamide (TOPA) and hexakis(2,3,6-tri-O-octyl)-alpha-cyclodextrin (OCD), were applied in poly(vinyl)chloride (PVC)-based liquid membrane electrodes. Both types of neutral ionophores improve the sensitivity for all mentioned drugs when compared with a tetrakis(p-chlorophenyl)borate (BOR)-based electrode as well as with single wavelength UV detection. Detection limits (S/N=3) of 2.6 x 10(-10) mol l(-1) (injected concentration) for the highly hydrophobic bromhexine were achieved with the TOPA-based electrode and a cyano reversed-phase (RP)-HPLC with Uptisphere UP5CN-25QS silica column (250 x 4.6 mm i.d.) eluted with acetonitrile (AcN)-ethanol-perchloric acid (1.66 mM) (60:2:38, v/v/v) (pH* 2.45). Comparable result was obtained with OCD-based electrodes and an XTerra RP18 hybrid silica-polymer column eluted with AcN-phosphoric acid (20 mM) (25:75, v/v) (pH* 2.60). In the mobile phases containing 60-75% v/v AcN or methanol, stable and reproducible response of both types of neutral ionophore-based electrodes was observed for at least 3 days. The results of the validated procedure for reliable simultaneous determination of the drugs in fortified representative samples of pharmaceuticals were also presented.
authors.affiliation: Faculty of Science and Biomedicine, Department of Chemistry, University of Antwerp RUCA, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. bazylak@ruca.uc.ac.be
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Bazylak
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Nagels
mesh_terms: D000551:Ambroxol / Q000032:analysis* / Q000737:chemistry; D001964:Bromhexine / Q000032:analysis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002976:Clenbuterol / Q000032:analysis* / Q000737:chemistry; D004563:Electrochemistry; D011199:Potentiometry / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000551:Ambroxol; D001964:Bromhexine; D002976:Clenbuterol