Lipophilic Salt Research Articles

Phosphonium Salt Displays Cytotoxic Effects Against Human Cancer Cell Lines.

In the present work, we investigated the cytotoxic activity of lipophilic phosphonium salt (11- methoxy11-oxo-undecyl) triphenylphosphonium bromide (MUTP) as well as of the two new phosphine oxide salts, 3,3'-(methylphosphoryl) dibenzenaminium chloride (SBAMPO) and 3,3' (phenylphosphoryl) dibenzenaminium chloride (SBAPPO) on the proliferation of breast cancer cell line (MCF-7) and human uterin cervix adenocarcinoma cells (HeLa). We showed that only MUTP exhibits antiproliferative effects on both cell lines, without affecting the normal breast epithelial cell proliferation. More specifically, we demonstrated that MUTP treatment of breast cancer cells is associated with impaired cell-cycle progression and metabolically induces mitochondrial damage and triggers apoptotic cell death in MCF-7 and HeLa cells. Taken together, these findings suggest that MUTP may be capable of selectively targeting neoplastic cell growth and therefore has potential applications as anticancer agent.

Membrane interactions of ionic liquids and imidazolium salts.

Room-temperature ionic liquids (RTILs) have attracted considerable attention in recent years due to their versatile properties such as negligible volatility, inflammability, high extractive selectivity and thermal stability. In general, RTILs are organic salts with a melting point below ~100°C determined by the asymmetry of at least one of their ions. Due to their amphiphilic character, strong interactions with biological materials can be expected. However, rising attention has appeared towards their similarity and interaction with biomolecules. By employing structural modifications, the biochemical properties of RTILs can be designed to mimic lipid structures and to tune their hydrophobicity towards a lipophilic behavior. This is evident for the interaction with lipid-membranes where some of these compounds present membrane-disturbing effects or cellular toxicity. Moreover, they can form micelles or lipid-like bilayer structures by themselves. Both aspects, cellular effects and membrane-forming capacities, of a novel class of lipophilic imidazolium salts will be discussed.

Manual and Flow-Injection Detection/Quantification of Polyquaterniums via Fully Reversible Polyion-Sensitive Polymeric Membrane-Based Ion-Selective Electrodes.

The detection of four different polyquaterniums (PQs) using a fully reversible potentiometric polyion sensor in three different detection modes is described. The polyion sensing "pulstrodes" serve as the detector for direct dose-response experiments, beaker titrations, and in a flow-injection analysis (FIA) system. Direct polycation response toward PQ-2, PQ-6, PQ-10, and poly(2-methacryloxyethyltrimethylammonium) chloride (PMETAC) yields characteristic information about each PQ species (e.g., relative charge densities, etc.) via syringe pump addition of each PQ species to a background electrolyte solution. Quantitative titrations are performed using a syringe pump to deliver heparin as the polyanion titrant to quantify all four PQs at μg/mL levels. Both the direct and indirect methods incorporate the use of a three-electrode system including counter, double junction reference, and working electrodes. The working electrode possesses a plasticized poly(vinyl chloride) (PVC) membrane containing the neutral lipophilic salt of dinonylnaphthalenesulfonate (DNNS-) tridodecylmethylammonium (TDMA+). Further, the titration method is shown to be useful to quantify PQ-6 levels in recreational swimming pool water collected in Ann Arbor, MI. Finally, a FIA system equipped with a pulstrode detector is used to demonstrate the ability to potentially quantify PQ levels via a more streamlined and semiautomated testing platform.

Enantioselective Additions of Stabilized Carbanions to Imines Generated from α-Amido Sulfones By Using Lipophilic Salts of Chiral Tris(1,2-diphenylethylenediamine) Cobalt(III) Trications as Hydrogen Bond Donor Catalysts

The enantiopure salt ∆-[Co((S,S)-dpen)3]3+ 2Cl–BArf – [BArf = B(3,5-C6H3(CF3)2)4] is an effective hydrogen bond donor catalyst (10 mol%, r.t., CH2Cl2) for enantioselective additions of dialkyl malonates to Boc-derivatized aryl imines generated from sulfones [ArCH(SO2Ph)NHBoc] in the presence of K2CO3 (ten examples, 91–97% isolated yields, 87–99% ee). The diastereomeric salt Λ-[Co((S,S)-dpen)3]3+ 2Cl–BArf20 – [BArf20 – = B(C6F5)4 –] is similarly applied to additions of nitroalkanes (four examples, 89–93% isolated yields, 79–91% ee). Precautions to exclude air or moisture are unnecessary.

Transformation of Biopharmaceutical Classification System Class I and III Drugs Into Ionic Liquids and Lipophilic Salts for Enhanced Developability Using Lipid Formulations

Higher lipid solubility of lipophilic salt forms creates new product development opportunities for high-dose liquid-filled capsules. The purpose of this study is to determine if lipophilic salts of Biopharmaceutical Classification System (BCS) Class I amlodipine and BCS Class III fexofenadine, ranitidine, and metformin were better lipid formulation candidates than existing commercial salts. Lipophilic salts were prepared from lipophilic anions and commercial HCl or besylate salt forms, as verified by 1H-NMR. Thermal properties were assessed by differential scanning calorimetry and hot-stage microscopy. X-ray diffraction and polarized light microscopy were used to confirm the salt's physical form. All lipophilic salt forms were substantially more lipid-soluble (typically >10-fold) when compared to commercial salts. For example, amlodipine concentrations in lipidic excipients were limited to <5-10 mg/g when using the besylate salt but could be increased to >100 mg/g when using the docusate salt. Higher lipid solubility of the lipophilic salts of each drug translated to higher drug loadings in lipid formulations. In vitro tests showed that lipophilic salts solubilized in a lipid formulation resulted in dispersion behavior that was at least as rapid as the dissolution rates of conventional salts. This study confirmed the applicability of forming lipophilic salts of BCS I and III drugs to promote the utility of lipid-based delivery systems.

Lipophilic salts of poorly soluble compounds to enable high-dose lipidic SEDDS formulations in drug discovery

Self-emulsifying drug delivery systems (SEDDS) have been used to solubilize poorly water-soluble drugs to improve exposure in high-dose pharmacokinetic (PK) and toxicokinetic (TK) studies. However, the absorbable dose is often limited by drug solubility in the lipidic SEDDS vehicle. This study focuses on increasing solubility and drug loading of ionizable drugs in SEDDS vehicles using lipophilic counterions to prepare lipophilic salts of drugs. SEDDS formulations of two lipophilic salts—atazanavir-2-naphthalene sulfonic acid (ATV-2-NSA) and atazanavir-dioctyl sulfosuccinic acid (ATV-Doc)—were characterized and their performance compared to atazanavir (ATV) free base formulated as an aqueous crystalline suspension, an organic solution, and a SEDDS suspension, using in vitro, in vivo, and in silico methods. ATV-2-NSA exhibited ∼6-fold increased solubility in a SEDDS vehicle, allowing emulsion dosing at 12mg/mL. In rat PK studies at 60mg/kg, the ATV-2-NSA SEDDS emulsion had comparable exposure to the free-base solution, but with less variability, and had better exposure at high dose than aqueous suspensions of ATV free base. Trends in dose-dependent exposure for various formulations were consistent with GastroPlus™ modeling. Results suggest use of lipophilic salts is a valuable approach for delivering poorly soluble compounds at high doses in Discovery.

Dualism of Sensitivity and Selectivity of Porphyrin Dimers in Electroanalysis

This work uncovers the application of porphyrin dimers for the use in electroanalysis, such as potentiometric determination of ions. It also puts in question a current perception of an occurrence of the super-Nernstian response, as a result of the possible dimerization of single porphyrins within an ion-selective membrane. To study that, four various porphyrin dimers were used as ionophores, namely, freebase-freebase, Zn-Zn, Zn-freebase, and freebase-Zn. Since the Zn-freebase and freebase-Zn porphyrin dimers carried both anion- and cation-sensitive porphyrin units, their application in ISEs was utilized in both anion- and cation-sensitive sensors. With respect to the lipophilic salt added, both porphyrins dimers were found anion- and cation-sensitive. This allowed using a single molecule as novel type of versatile ionophore (anion- and cation-selective), simply by varying the membrane composition. All anion-sensitive sensors were perchlorate-sensitive, while the cation-selective sensors were silver-sensitive. The selectivity of the sensors depended primarily on the porphyrin dimers in the ion-selective membrane. Furthermore, the selectivity of cation-sensitive dimer based sensors was found significantly superior to the ones measured for the single porphyrin unit based sensors (precursors of the porphyrin dimers). Thus, the dimerization of single porphyrins may actually be a factor to increase or modulate porphyrin selectivity. Moreover, in the case of cation-sensitive sensors, the selectivity vastly depended on the order of porphyrin units in the dimer. This opens a new approach of regulating and adjusting sensitivity and selectivity of the sensor through the application of complex porphyrin systems with more than one porphyrin units with mix sensitive porphyrins.

Electrogenic transport by lipophilic guanidinium salts as anion carriers in bilayer membranes

Anion transport by four isomers of tetradecylguanidinium in vesicle bilayer membranes was investigated by ion-selective electrode and pH-sensitive fluorescence methods. On a macroscopic scale, these carriers mediate hydroxide-anion antiport. In the absence of an externally imposed ionic gradient, the carriers produce a pH gradient due to rapid partition-deprotonation of the carrier and diffusion of the guanidine conjugate base. The formally coupled anion transport is slow relative to this process, and the system exhibits a corresponding membrane polarisation detected with potential-sensitive fluorescent dyes. Selective anion transport in competition with the efficient hydroxide transport is detected only with relatively easily extracted anions and N,N′-disubstituted isomers. Membrane polarisation changes can be deduced from simple equivalent circuits derived from the Goldman–Hodgkin–Katz voltage equation.

Syntheses of Families of Enantiopure and Diastereopure Cobalt Catalysts Derived from Trications of the Formula [Co(NH2CHArCHArNH2)3]3.

Aerobic reactions of CoX2 (X = OAc, Cl) or Co(ClO4)2 with (S,S)-1,2-diphenylethylenediamine [(S,S)-dpen] in CH3OH, followed by HCl or HClO4 additions, give the diastereomeric lipophobic salts Λ-[Co((S,S)-dpen)3]3+3Cl- [Λ-(S,S)-13+3Cl-] or Δ-(S,S)-13+3ClO4- (60-65%) with high degrees of selectivity. Anion metatheses (room temperature) and equilibrations (charcoal, CH3OH, 70 °C) show that the former is more stable than Δ-(S,S)-13+3Cl-, and the latter is more stable than Λ-(S,S)-13+3ClO4-. Additional anion metatheses lead to large families of lipophilic salts Λ- and Δ-(S,S)-13+2X-X'- [X/X' = Cl/BArf [BArf = B(3,5-C6H3(CF3)2)4], PF6/BArf, BF4/BArf, PhBF3/BArf, Cl/BArf20 [BArf20 = B(C6F5)4], BArf/BArf, BArf20/BArf20, BF4/BF4, PF6/PF6]. Mixed salts of the formula Λ- and Δ-[Co((S,S)-NH2CHArCHArNH2)3]3+2Cl-BArf- are similarly prepared (Ar = 4-C6H4n-Bu, 4-C6H4Cl, 4-C6H4CF3, 4-C6H4OCH3, α-naphthyl, β-naphthyl, 2-C6H4OBn). The diastereotopic NHH' protons exhibit different 1H NMR signals; one shifts far downfield when X/X' = Cl/BArf (δ ca. 8.0 vs 4.0 ppm). This is believed to arise from hydrogen bonding between the two Cl- anions and the two C3 faces of the D3-symmetric trication, each of which feature three synperiplanar NH groups. When all of the anions are poor hydrogen-bond acceptors (e.g., BArf-, BF4-, ClO4-), equilibria favor Δ diastereomers.

Evaluation of taste masking effect of diclofenac using sweeteners and cyclodextrin by a potentiometric electronic tongue

In this work a potentiometric electronic tongue based on classical ion-selective electrodes (6 types) and solid contact electrodes (2 types) was applied. The classical electrodes based on PVC membrane with other plasticizers exhibited cation-, anion-, amine-, and carbonate sensitivity, while the solid contact electrodes based on different lipophilic salts established diclofenac sensitivity. These sensors were used to assess the taste masking efficiency of diclofenac using selected sweeteners and cyclodextrin. Various amounts of four sweeteners (namely: sucrose, lactose, acesulfame K, sodium saccharin) as well as 2-hydroxypropyl-β-cyclodextrin were applied to mask the bitter taste of diclofenac. The signals of the sensor array registered during the experiments were processed by the Principal Component Analysis. The results obtained i.e. the chemical images of the samples indicated that the taste masking effect was the most pronounced for cyclodextrin, acesulfame K, sodium saccharin and for sucrose at higher concentration, whereas was almost negligible in the case of the presence of lactose in solution.

Structural changes in emulsion-bound bovine beta-lactoglobulin affect its proteolysis and immunoreactivity

Adsorption on the surface of sub-micrometric oil droplets resulted in significant changes in the tertiary structure of bovine beta-lactoglobulin (BLG), a whey protein broadly used as a food ingredient and a major food allergen. The adsorbed protein had increased sensitivity to trypsin, and increased immunoreactivity towards specific monoclonal antibodies. In spite of the extensive tryptic breakdown of emulsion-bound BLG, some sequence stretches in BLG became trypsin-insensitive upon absorption of the protein on the fat droplets. As a consequence – at contrast with free BLG – proteolysis of emulsion-bound BLG did not decrease the immunoreactivity of the protein, and some of the large peptides generated by trypsinolysis of emulsion-bound BLG were still recognizable by specific monoclonal antibodies. Structural changes occurring in emulsion-bound BLG and their consequences are discussed in comparison with those occurring when the tertiary structure of BLG is modified by lipophilic salts, by urea, or upon interaction with solid hydrophobic surfaces. Such a comparison highlights the relevance of situation-specific structural modifications, that in turn may affect physiologically relevant features of the protein.

Trypanocidal action of bisphosphonium salts through a mitochondrial target in bloodstream form Trypanosoma brucei

Lipophilic bisphosphonium salts are among the most promising antiprotozoal leads currently under investigation. As part of their preclinical evaluation we here report on their mode of action against African trypanosomes, the etiological agents of sleeping sickness. The bisphosphonium compounds CD38 and AHI-9 exhibited rapid inhibition of Trypanosoma brucei growth, apparently the result of cell cycle arrest that blocked the replication of mitochondrial DNA, contained in the kinetoplast, thereby preventing the initiation of S-phase. Incubation with either compound led to a rapid reduction in mitochondrial membrane potential, and ATP levels decreased by approximately 50% within 1 h. Between 4 and 8 h, cellular calcium levels increased, consistent with release from the depolarized mitochondria. Within the mitochondria, the Succinate Dehydrogenase complex (SDH) was investigated as a target for bisphosphonium salts, but while its subunit 1 (SDH1) was present at low levels in the bloodstream form trypanosomes, the assembled complex was hardly detectable. RNAi knockdown of the SDH1 subunit produced no growth phenotype, either in bloodstream or in the procyclic (insect) forms and we conclude that in trypanosomes SDH is not the target for bisphosphonium salts. Instead, the compounds inhibited ATP production in intact mitochondria, as well as the purified F1 ATPase, to a level that was similar to 1 mM azide. Co-incubation with azide and bisphosphonium compounds did not inhibit ATPase activity more than either product alone. The results show that, in T. brucei, bisphosphonium compounds do not principally act on succinate dehydrogenase but on the mitochondrial FoF1 ATPase.

Functionalized β-cyclodextrin based potentiometric sensor for naproxen determination

Potentiometric sensors based on neutral β-cyclodextrins: (2-hydroxypropyl)-β-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, heptakis(2,3,6-tri-O-benzoyl)-β-cyclodextrin and anionic β-cyclodextrin: (2-hydroxy-3-N,N,N-trimethylamino)propyl-β-cyclodextrin chloride for naproxen are described. Inclusion complexes of naproxen with the above-mentioned cyclodextrins were studied using IR spectroscopy. The electrode surface was made from PVC membranes doped with the appropriate β-cyclodextrin as ionophores and quaternary ammonium chlorides as positive charge additives that were dispersed in plasticizers. The optimum membrane contains heptakis(2,3,6-tri-O-benzoyl)-β-cyclodextrin, o-nitrophenyloctyl ether and tetraoctyl ammonium chloride as a lipophilic salt. The electrode is characterized by a Nernstian response slope of −59.0±0.5mVdecade−1 over the linear range of 5.0×10−5–1.0×10−2molL−1 and the detection limit 1.0×10−5molL−1, as well as the response time 10s. It can be used in the pH range 6.2–8.5 for 10months without any considerable deterioration. Incorporation of β-cyclodextrins improved the electrode selectivity towards naproxen ions from several inorganic and organic interferents and some common drug excipients due to concovalent interactions (host molecule–guest molecule). The notable advantages of the naproxen-selective electrode include its high sensitivity, high selectivity, cost-effectiveness as well as accurate and comfortable application in drug analysis and milk samples.

Reversible Electrochemical Sensor for Detection of High-Charge Density Polyanion Contaminants in Heparin.

We present a simple, rapid, and inexpensive electrochemical sensor based on a reversible pulsed chronopotentiometric polyanion-selective membrane electrode for the detection and quantification of oversulfated chondroitin sulfate (OSCS) and other high charge-density polyanions that could potentially be used to adulterate heparin. The membrane is free of ion exchanger and is formulated with plasticized poly(vinyl chloride) (PVC) and an inert lipophilic salt, tridodecylmethylammonium-dinonylnaphthaline sulfonate (TDMA-DNNS). The neutral salt is used to reduce membrane resistance and to ensure reversibility of the sensor. More importantly, TDMA(+) is used as the recognition element for the polyanions. Here an anodic galvanostatic current pulse is applied across the membrane to cause the extraction of the polyanions from the sample into the membrane and potential is measured at the sample-membrane interface. The measured electromotive force (emf) is proportional to the concentration and the charge density of the polyanions. High charge-density polyanion contaminants and impurities in heparin can be detected using this method since the overall equilibrium potential response of polyions increases with increasing charge density of the polyions. Here, first the potential response of pure heparin is measured at a saturation concentration, the concentration beyond which further addition of heparin does not produce a change in potential response. Then the potential response of heparin tainted with different quantities of the high charge-density contaminant is measured at a fixed total polyion concentration (heparin concentration + contaminant concentration). The latter gives a greater negative potential response due to the presence of the high charge-density contaminant. The increase in the negative potential response can be used for detection and quantification of high charge-density contaminants in heparin. We demonstrate here that 0.3% (w/w) OSCS as well as 0.1% (w/w) dextran sulfate can be detected in heparin at 20-mg/mL total polyion concentration. It has also been shown that 1% (w/w) of dextran sulfate can readily be detected in heparin at only 2-mg/mL total polyanion concentration with a linear response (R(2) = 0.994).

Paper-based potentiometric ion sensors constructed on ink-jet printed gold electrodes

Printed electrodes on a recyclable low-cost coated paper were used as a platform for constructing potentiometric ion sensors consisting of an ion-selective electrode (ISE) and a reference electrode (RE). The reference and working electrodes were printed by using a stable suspension of gold nanoparticles (AuNP) as the ink. Sintering turned the printed electrodes conductive. A poly(3,4-ethylenedioxythiophene) (PEDOT) layer, with poly(styrene sulfonate) (PSS) ions as counterions was deposited on the gold electrodes by electropolymerization, drop-casting or ink-jet printing. The reference electrode was prepared by further coating the PEDOT(PSS) layer with a poly(vinyl chloride) (PVC) membrane containing a lipophilic salt, tetrabutylammonium tetrabutylborate (TBA-TBB), thus resulting in a solid-contact reference electrode (SCRE). The working electrode was modified by coating the PEDOT(PSS) layer with a K+-selective membrane, to obtain a solid-contact K+-ISE. The electrochemical characteristics of the resulting electrode systems were studied by amperometric, potentiometric and electrochemical impedance spectroscopic (EIS) measurements. The potentiometric response toward K+ ions was additionally studied. The surface structure of the PEDOT(PSS) layers deposited by the different methods was studied with atomic force microscopic (AFM) measurements. It was shown that a well-functioning planar electrode platform with good electrochemical characteristics could be prepared by ink-jet printing in a repeatable manner. The planar electrode platform presented here offers a user-friendly and ecological alternative to perform chemical analysis from small sample volumes.

Anti-tumor activity of lipophilic imidazolium salts on select NSCLC cell lines.

The anti-tumor activity of imidazolium salts is highly dependent upon the substituents on the nitrogen atoms of the imidazolium cation. We have synthesized and characterized a series of naphthalene-substituted imidazolium salts and tested them against a variety of non-smallcell lung cancer cell lines. Several of these complexes displayed anticancer activity comparable to cisplatin. These compounds induced apoptosis in the NCI-H460 cell line as determined by Annexin V staining, caspase-3, and PARP cleavage. These results strongly suggest that this class of compounds can serve as potent chemotherapeutic agents.

Fabrication of novel sensors based on a synthesized acyclic pyridine derivative ionophore for potentiometric monitoring of copper

Two synthesized acyclic di-peptide pyridine derivatives were used as an effective neutral ionophore, and potassium p,chloro tetraphenylborate (KpClTPB) as anionic excluder for copper-selective poly(vinyl) chloride (PVC) membrane sensors. The sensors exhibited fast and stable near-Nernstian response over a concentration range of 8.0 × 10−6 mol L−1 to 1.0 × 10−2 mol L−1 Cu2+ with a cationic slope of 26.2–23.3 mV per decade at a pH range 3.5–5.5 with a lower detection limit of 0.32–0.57 μg mL−1. Effects of plasticizers, lipophilic salts and various foreign common ions were also tested. The validation of the method revealed good performance characteristics, including long life span, good selectivity for Cu2+ over a wide variety of other alkalis, alkali earth and transition metal ions (e.g. Na+, K+, Ag+, Hg2+, Ca2+, Zn2+, Cd2+, Co2+, Pb2+, Ni2+, Fe2+, Mg2+, Fe3+), long term stability, high reproducibility, fast response, low detection limit, wide measurement range, acceptable accuracy and precision. The sensors were successfully applied to direct determination of copper(II) in water and waste water samples. The results agreed fairly well with data obtained using atomic absorption spectrometry.

Electrochemical control of the standard potential of solid-contact ion-selective electrodes having a conducting polymer as ion-to-electron transducer

This work addresses the well-known problem of variations in the standard potential (E°) of solid-contact ion-selective electrodes (SC-ISEs) that have a conducting polymer (CP) as ion-to-electron transducer covered by a polymeric ion-selective membrane. Poly(3,4-ethylene dioxythiophene) doped with poly(sodium 4-styrenesulfonate), i.e. PEDOT(PSS), was electrodeposited on glassy carbon (GC) disk electrodes and used as the solid contact for three different types of PVC-based membranes in order to elucidate the possibility to electrochemically control E° for this type of SC-ISE. The GC/PEDOT(PSS) electrode was thus coated with potassium-selective membranes with and without the lipophilic salt tetradocedylammonium tetrakis(4-clorophenyl)borate (ETH-500) and by a cation-sensitive membrane without ionophore. The results show that the standard potential of the studied types of SC-ISEs can be shifted by applying a potential that deviates from the open-circuit potential of the electrode in the chosen electrolyte solution or by applying current pulses in the nA range.

Different Permeability of Potassium Salts across the Blood-Brain Barrier Follows the Hofmeister Series

The passage of ions across biological membranes is regulated by passive and active mechanisms. Passive ion diffusion into organs depends on the ion-pairing properties of salts present in the serum. Potassium ions could affect brain activity by crossing the blood-brain barrier (BBB) and its accumulation in the extracellular cerebral space could precipitate seizures. In the present study, we analyze passive diffusion of a series of potassium salts in the in vitro isolated guinea pig brain preparation. Different potassium counter-anions confer ion-pairing and lipophilicity properties that modulate membrane diffusion of the salt. Extracellular recordings in different cortical areas demonstrated the presence of epileptiform activities that strongly relate to anion identity, following the qualitative order of the Hofmeister series. Indeed, highly lipophilic salts that easily cross the BBB enhanced extracellular potassium concentration measured by ion-selective electrodes and were the most effective pro-epileptic species. This study constitutes a novel contribution for the understanding of the potential epileptogenicity of potassium salts and, more generally, of the role of counter-anions in the passive passage of salts through biological membranes.

New potentiometric sensors based on selective recognition sites for determination of ephedrine in some pharmaceuticals and biological fluids

New cost-effective potentiometric membrane sensors with cylindrical configuration responsive to ephedrine are described. The sensors setup is, based on the use of triacetyl-β-cyclodextrin [(triacetyl-β-CD)] as a neutral ionophore embedded in a plasticized poly (vinyl chloride) (PVC) matrix (sensor I) and carboxylated poly(vinyl chloride) [(PVC–COOH)] as a simultaneous plastic matrix and ion exchanger (sensor II). Both sensors showed significant enhancement of response towards ephedrinium cation (EPD+) over a concentration range of 3.0×10−5–8.0×10−3molL−1 at pH 4–9 and 3–8 with low detection limits of 5.7×10−6 and 6.2×10−6molL−1 for sensors (I) and (II), respectively. The sensors displayed near-Nernstian cationic slope of 57.0 and 55.6mV decade−1 for EPD+ and the effects of lipophilic salts and various foreign common ions were examined. The sensors were also satisfactorily used as tubular detectors in a double channel flow injection system. The intrinsic characteristics of the detectors in a low dispersion manifold under hydrodynamic mode of operation were determined and compared with data obtained under batch mode of operation. Validation of the method revealed good performance characteristics including long life span, good selectivity for EPD+ over a wide variety of other organic compounds, long term stability, high reproducibility, fast response, low detection limit, wide measurement range, acceptable accuracy and precision. Applications of the sensors to the determination of EPD+ in pharmaceutical formulations and spiked biological fluid samples were carried out and compared with standard techniques. Notably, the sensors introduced offer several advantages over many of those previously described that are amenable to quality control/quality assurance assessment of the homogeneity, stability and purity of ephedrine drug tablets.