Ion Pair Acidities Research Articles

Development of levamlodipine long-acting patches based on an ion-pair strategy: Investigation of the mechanism for reducing skin irritation

The aim of this study was to develop a long-acting transdermal patch of levamlodipine (LAM) using an ion-pair strategy to reduce the skin irritation induced by topical application of LAM and explore the mechanism underlying the improvement of skin irritation. The formulation was optimized through porcine in vitro transdermal experiments and rabbit in vivo skin irritation tests. The obtained formulation consisted of poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl) acrylamide) (PENH) as the adhesive matrix, 13.00 % levamlodipine-sorbic acid ion-pair complex (LAM-SA) (w/w), and 10 % isopropyl myristate (IPM) (w/w), with a patch thickness of 70 μm, achieving an erythema index of 188 for rabbit skin and 117–187 for human skin (264 for rabbit skin and 110–260 for human skin in the absence of sorbic acid (SA)). In vivo rabbit and human skin erythema analysis and H&E staining verified that the optimized ion-pair patch effectively reduced skin irritation. Drug distribution experiments in the skin, ATR-FTIR, and molecular simulation were used to characterize the mechanism by which the ion-pair reduced skin irritation. Excessive accumulation of LAM in the epidermis induced secondary structural changes in keratin, resulting in skin barrier damage and inflammatory response. The formation of the LAM-SA ion pair altered physicochemical properties of LAM, reducing drug retention in the epidermis and, thereby, reducing skin irritation. This study demonstrated the potential of the ion-pair strategy to improve the safety of transdermal drug delivery system (TDDS) and provided a means for reducing skin irritation caused by the active pharmaceutical ingredient (API) itself.

Chirality in Singlet Fission: Controlling Singlet Fission in Aqueous Nanoparticles of Tetracenedicarboxylic Acid Ion Pairs.

The singlet fission characteristics of aqueous nanoparticles, self-assembled from ion pairs of tetracene dicarboxylic acid and various amines with or without chirality, are thoroughly investigated. The structure of the ammonium molecule, the counterion, is found to play a decisive role in determining the molecular orientation of the ion pairs and its regularity, spectroscopic properties, the strength of the intermolecular coupling between the tetracene chromophores, and the consequent singlet fission process. Using chiral amines has led to the formation of crystalline nanosheets and efficient singlet fission with a triplet quantum yield as high as 133% ±20% and a rate constant of 6.99×109s-1. The chiral ion pairs also provide a separation channel to free triplets with yields as high as 33% ±10%. In contrast, nanoparticles with achiral counterions do not show singlet fission, which gave low or high fluorescence quantum yields depending on the size of the counterions. The racemic ion pair produces a correlated triplet pair intermediate by singlet fission, but no decorrelation into two free triplets is observed, as triplet-triplet annihilation dominates. The introduction of chirality enables higher control over orientation and singlet fission in self-assembled chromophores. It provides new design guidelines for singlet fission materials.

Study on determination methods and analysis of micronutrients in take-away meals

To comprehensively analyze the trace nutrient contents in take-away meals, the simultaneous detection method of common vitamins in take-away meals were explored based on the samples' matrix, and the content of trace nutrients in take-away meals was analyzed combined with inductively coupled plasma-mass spectrometry(ICP-MS) detection of common elements. Fifty-seven take-away meals were collected randomly and analyzed. Vitamins were determined by high performance liquid chromatography-ultraviolet detector tandem fluorescence detector after pretreatment of samples including enzymatic digestion, hydrolysis and extraction. The separation was performed on a C_(18) column(250 mm×4.6 mm, 5 μm) with ion-pair acid reagents as the mobile phase for water-soluble vitamins and methanol for fat-soluble vitamins. Vitamin B_1, vitamin B_2, nicotinic acid, nicotinamide and vitamin A were detected by ultraviolet detector(UVD), while vitamin B_6 and E by fluorescence detector(FLD). Elemental analysis of calcium, magnesium, sodium, potassium, zinc, selenium and copper in the take-away meals was carried out according to GB 5009.268-2016 by ICP-MS to comprehensively evaluate the contents of micronutrients. Through optimization of chromatography and sample pretreatment conditions, the sensitivity of the established detection method can meet the needs of micronutrient evaluation with the detection limits and quantification limits of vitamins in the range of 0.002-0.098 mg/100 g and 0.007-0.327 mg/100 g, respectively. Good precision was obtained(<10%). The spiked recovery rates were 80.5%-103.8%(n=6). The result showed that the contents of micronutrients in take-away meals were generally low. The detection rates of vitamins ranged from 21.1% to 98.2%. The proposed method is simple and sensitive, and the contents of vitamins and elements determined were low in the collected take-away meals.

Ion pair self-assembly composed of polyamidoamine dendrimer and phenylthio acetic acid and its temperature and oxidation-responsive release property

Polyamidoamine (PAMAM) dendrimer/phenylthio acetic acid (PTA) ion pair could be generated when the amino/carboxyl group ratio was 3/7 to 1/9. The chemical shifts on 1H NMR and FT-IR spectra suggested that PTA interacted ionically with PAMAM. The PTA was oxidized to sulfoxide and sulfone by H2O2, evidenced by 1H NMR and FT-IR spectroscopy. The ion pair exhibited upper critical solution temperature (UCST) and air/water interface-active which could decrease upon PTA oxidation. When the medium temperature was higher than the UCST, the substantial release of dye loaded in IPSAM took place in the H2O2 solution.

Switchable deep eutectic solvent as green and efficient media for liquid-phase microextraction of phenoxyacetic acid herbicides in water and food matrices

In this work, a switchable deep eutectic solvent (SDES) based on fatty acid and polyetheramine ion pair was prepared for liquid-phase microextraction (LPME) of phenoxyacetic acid herbicides in drinking water, beverage and honey matrices. The as-synthesized SDES equipped with an interesting characteristic of fast and reversible polarity switching, achieving homogeneous extraction and rapid bi-phase separation simultaneously. Several key parameters affecting the extraction performance were investigated comprehensively by Box-Behnken design. Under the optimal conditions, the method exhibited excellent linearity (15–4000 μg L−1), low detection limits (3–5 μg L−1), desirable precision (RSD < 8.1 %), and satisfactory recovery (72.6–98.7 %). More importantly, the introduction of SDES can simplify the pre-treatment procedure, shorten extraction time (4 min), and avoid the usage of traditional organic solvent during the whole extraction process. In addition, the switching mechanism of SDES was characterized by FT-IR and 1H NMR, and the forming mechanism of SDES was investigated using density-functional theory. The green of the method was estimated using the analytical ecological scale, the analytical green calculator, and the green analytical procedure index. The cytotoxicity of SDES was investigated and the result displayed that toxicity of the SDES was very low with the EC50 > 500 mg/L. Therefore, the proposed method was green and efficient and revealed considerable application prospects for the extraction of trace analytes from complex materials.

In vitro and in vivo anti-tumor extrapolation of one pot engineered stimuli-responsive poly(ethylenimine) and (phenylthio) acetic acid ion pair micelles for smart delivery of doxorubicin and indocyanine green

In vitro and in vivo anti-tumor extrapolation of one pot engineered stimuli-responsive poly(ethylenimine) and (phenylthio) acetic acid ion pair micelles for smart delivery of doxorubicin and indocyanine green

Efficiency of mitochondrial uncoupling by modified butyltriphenylphosphonium cations and fatty acids correlates with lipophilicity of cations: Protonophoric vs leakage mechanisms

In order to determine the share of protonophoric activity in the uncoupling action of lipophilic cations a number of analogues of butyltriphenylphosphonium with substitutions in phenyl rings (C4TPP-X) were studied on isolated rat liver mitochondria and model lipid membranes. An increase in the rate of respiration and a decrease in the membrane potential of isolated mitochondria were observed for all the studied cations, the efficiency of these processes was significantly enhanced in the presence of fatty acids and correlated with the octanol-water partition coefficient of the cations. The ability of C4TPP-X cations to induce proton transport across the lipid membrane of liposomes loaded with a pH-sensitive fluorescent dye increased also with their lipophilicity and depended on the presence of palmitic acid in the liposome membrane. Of all the cations, only butyl[tri(3,5-dimethylphenyl)]phosphonium (C4TPP-diMe) was able to induce proton transport by the mechanism of formation of a cation-fatty acid ion pair on planar bilayer lipid membranes and liposomes. The rate of oxygen consumption by mitochondria in the presence of C4TPP-diMe increased to the maximum values corresponding to conventional uncouplers; for all other cations the maximum uncoupling rates were significantly lower. We assume that the studied cations of the C4TPP-X series, with the exception of C4TPP-diMe at low concentrations, cause nonspecific leak of ions through lipid model and biological membranes which is significantly enhanced in the presence of fatty acids.

Development and validation of an ultra-high performance liquid chromatography coupled to tandem mass spectrometry method for the quantification of the antileishmanial drug paromomycin in human skin tissue

Bioanalytical assay development and validation procedures were performed to quantify antiprotozoal drug paromomycin in human skin tissue by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. Paromomycin, an aminoglycoside drug, is administered intra-muscularly and used in the treatment of multiple clinical presentations of the neglected tropical disease leishmaniasis. It is currently studied in the treatment of post-kala-azar dermal leishmaniasis, a disease where the Leishmania parasites divide and reside in the skin. We present a target-site bioanalytical method to accurately quantify paromomycin in human skin tissue, with the clinical purpose of quantifying paromomycin in skin biopsies from post-kala-azar dermal leishmaniasis patients originating from Sudan. Enzymatic digestion using collagenase A incubated at 37 °C overnight was employed as homogenization method to produce skin tissue homogenates. Further sample preparation was performed by protein precipitation using trichloroacetic acid and a dilution step. Final extracts were injected onto a C18 analytical column and isocratic heptafluorobutyric acid ion-pair separation and elution were employed. The chromatography system was coupled to a triple quadrupole mass spectrometer for detection. The method was validated in digestion solution over a linear range from 5 to 1000 ng/mL (r2 ≥ 0.9967) with the assay performance of accuracy and precision within acceptable criteria values as stated by the EMA guidelines. Furthermore, matrix effects were observed in human skin tissue and were corrected by the multiple deuterated paromomycin internal standard. No substantial IS-normalized matrix effect was detected along with relatively high sample preparation recovery. Consequently, digestion solution matrix serving as the preparation of calibration standards can be used as surrogate matrix for human skin tissue, which is convenient given the limited availability of control matrix. Finally, paromomycin was accurately quantified in skin of post-kala-azar dermal leishmaniasis patients originating from clinical trials in Sudan.

In Situ Preparation of Gold Nanoparticles Using Poly(ethylenimine)/(Phenylthio) Acetic Acid Ion Pair Self-assembly as a Reducing and a Capping Material and Its NIR–Responsive Release Property

In Situ Preparation of Gold Nanoparticles Using Poly(ethylenimine)/(Phenylthio) Acetic Acid Ion Pair Self-assembly as a Reducing and a Capping Material and Its NIR–Responsive Release Property

Thermo-sensitive self-assembly of poly(ethylene imine)/(phenylthio) acetic acid ion pair in surfactant solutions

Poly(ethylene imine)/(phenylthio) acetic acid (PEI/PTA) ion pairs exhibited an upper critical solution temperature (UCST) behavior in an aqueous solution and the UCST was higher as the PTA content was more. The UCST of the ion pair decreased with increasing Brij S100 (BS 100, a nonionic surfactant) concentration but increased with increasing cetylpridinium chloride (CPC, a cationic surfactant) and sodium lauroylsarcosinate (SLS, an anionic surfactant) concentration. TEM microscopy demonstrated BS 100 markedly reduced the size of PEI/PTA ion pair self-assembly (IPSAM) whereas CPC and SLS had little effect on the size and the integrity of IPSAM. 1H NMR spectroscopy showed the hydrophobic interaction among the phenyl groups of PEI/PTA ion pairs took place. It also demonstrated the hydrophobic interaction between BS 100 and PTA and the electrostatic interaction between CPC and PTA and between SLS and PEI occurred. X-ray photoelectron spectroscopy disclosed the PTA of PEI/PTA IPSAM could be readily oxidized by H2O2 even at a low concentration (e.g. 0.005%). IPSAM released its payload (i.e. nile red) in a temperature and oxidation-responsive manner. The surfactants (i.e. BS 100, CPC, and SLS) suppressed the thermally triggered release in a different way. The effectiveness of the surfactant to suppress the release was in the order of BS 100 > CPC > SLS. IPSAM released its content more extensively as H2O2 (an oxidizing agent) concentration was higher. The ionic surfactants (i.e. CPS and SLS) had little effect on the oxidation-induced release degree but the nonionic surfactant (BS 100) markedly suppressed the release degree.

Effect of Water on a Hydrophobic Deep Eutectic Solvent.

Deep eutectic solvents (DESs) formed by hydrogen bond donors and acceptors are a promising new class of solvents. Both hydrophilic and hydrophobic binary DESs readily absorb water, making them ternary mixtures, and a small water content is always inevitable under ambient conditions. We present a thorough study of a typical hydrophobic DES formed by a 1:2 mole ratio of tetrabutyl ammonium chloride and decanoic acid, focusing on the effects of a low water content caused by absorbed water vapor, using multinuclear NMR techniques, molecular modeling, and several other physicochemical techniques. Already very low water contents cause dynamic nanoscale phase segregation, reduce solvent viscosity and fragility, increase self-diffusion coefficients and conductivity, and enhance local dynamics. Water interferes with the hydrogen-bonding network between the chloride ions and carboxylic acid groups by solvating them, which enhances carboxylic acid self-correlation and ion pair formation between tetrabutyl ammonium and chloride. Simulations show that the component molar ratio can be varied, with an effect on the internal structure. The water-induced changes in the physical properties are beneficial for most prospective applications but water creates an acidic aqueous nanophase with a high halide ion concentration, which may have chemically adverse effects.

Poly (ethylenimine)/(phenylthio) acetic acid ion pair self-assembly incorporating indocyanine green and its NIR–responsive release property

Poly (ethylenimine)/(phenylthio) acetic acid ion pair self-assembly incorporating indocyanine green and its NIR–responsive release property

Self-assembly prepared using an ion pair of poly(ethylene imine) and (phenylthio) acetic acid as a drug carrier for oxidation, temperature, and NIR-responsive release

Poly(ethylene imine)/(phenylthio) acetic acid (PEI/PTA) ion pair whose the molar ratio of amino to carboxyl group ratio was 3/7 exhibited its upper critical solution temperature (UCST) around body temperature (37 ℃) at pH 7.0. The UCST decreased with increasing H2O2 concentration used to treat the ion pair (0 to 20 mM). Below the UCST, PEI/PTA ion pair was self-assembled into nanoparticles (IPSAM) possibly because the ion pair was amphiphilic and surface-active. The ion pair decreased in the surface activity and increased in the critical micelle concentration, when the sulfide of PTA was oxidized by H2O2. This could account for why the UCST decreased with increasing H2O2 concentration. IPSAM released its payload (i.e. nile red) in response to oxidation and temperature. Upon oxidation, the ion pair decreased in its UCST and IPSAM underwent dissolution, leading to a promoted release. Upon heating, the temperature increased above UCST, which caused IPSAM to be disassembled and release its payload. Gold nanoparticle (GNP) synthesized in situ was found to be bound to IPSAM. IPSAM bearing GNP exhibited a promoted release of its payload under near-infrared (NIR) irradiation. Heat generated by GNP would be able to disassemble IPSAM and enhance the release. Doxorubicin loaded in folated IPSAM exhibited a significant in vitro anti-cancer activity against KB cells. It could be effectively internalized into the cells, evidenced by fluorescence-activated cell sorting analysis and confocal laser scanning microscopy. When GNP was included in IPSAM, NIR irradiation led to further increase in the anti-cancer activity.

Unravelling moisture-induced CO2 chemisorption mechanisms in amine-modified sorbents at the molecular scale.

This work entails a comprehensive solid-state NMR and computational study of the influence of water and CO2 partial pressures on the CO2-adducts formed in amine-grafted silica sorbents. Our approach provides atomic level insights on hypothesised mechanisms for CO2 capture under dry and wet conditions in a tightly controlled atmosphere. The method used for sample preparation avoids the use of liquid water slurries, as performed in previous studies, enabling a molecular level understanding, by NMR, of the influence of controlled amounts of water vapor (down to ca. 0.7 kPa) in CO2 chemisorption processes. Details on the formation mechanism of moisture-induced CO2 species are provided aiming to study CO2 : H2O binary mixtures in amine-grafted silica sorbents. The interconversion between distinct chemisorbed CO2 species was quantitatively monitored by NMR under wet and dry conditions in silica sorbents grafted with amines possessing distinct bulkiness (primary and tertiary). Particular attention was given to two distinct carbonyl environments resonating at δC ∼161 and 155 ppm, as their presence and relative intensities are greatly affected by moisture depending on the experimental conditions. 1D and 2D NMR spectral assignments of both these 13C resonances were assisted by density functional theory calculations of 1H and 13C chemical shifts on model structures of alkylamines grafted onto the silica surface that validated various hydrogen-bonded CO2 species that may occur upon formation of bicarbonate, carbamic acid and alkylammonium carbamate ion pairs. Water is a key component in flue gas streams, playing a major role in CO2 speciation, and this work extends the current knowledge on chemisorbed CO2 structures and their stabilities under dry/wet conditions, on amine-modified solid surfaces.

Potentiometric determination of oxybutynin hydrochloride in pharmaceutical formulations at modified carbon paste electrodes

A new potentiometric sensitive and selective modified carbon paste (MCPE) electrodes based on phosphotungestic acid (PTA), sodium tetraphenyl borate (NaTPB), phosphomolybdic acid (PMA) or ammonium reineckate (RN) ion pairing agents for determination of (Ox.HCl) were developed. The proposed electrodes have a Nernstian slope values of 58.50±0.71, 58.71±1.20, 54.80±1.30 and 59.20±0.70 mV decade-1for electrodes modified with 20, 10, 5 and 10 mg of Ox-TPB (electrode I), Ox-RN (electrode II), Ox-PMA (electrode III) and Ox-PTA (electrode IV) ion pairs, respectively, with a dynamic drug concentration range at 25 (C was 1.0x10-5 - 1.0x10-2 mole L-1 with detection limit of 1.0× 10-5 mol L-1. The response of MCPEs were pH independent in the range 2.0-6.0 with a fast response time of 10 s for electrode I and 12 s for electrodes II-IV. The MCPEs showed a relatively long life time of 36 days. A pure and pharmaceutical formulation of Ox.HCl was quantified using calibration and standard addition methods and the obtained results agreed with that of the official HPLC method. Validation parameters were optimized according to ICH recommendations.

A novel organic reaction leading to new 2-N-substituted benzoic acid ion-pair. A combination of physicochemical and theoretical calculations approaches

The 2-aminobenzimidazole (ABZ)-2-N-propanoyl benzoic acid 1 which is an intermediate of synthesis of various heterocyclic compounds was synthesized. The structure of 1 was confirmed by FT-IR, NMR (1D and 2D) spectra and XRD. The molecular structure of compound 1 was characterized by single-crystal X-ray structure determination and theoretical calculations based on DFT, HF and MP2 methods. The NBO analysis was used mainly in order to study the influence of electronic delocalization on the mechanism. Experimental, DFT, HF and MP2/6-31G(d) optimized bond lengths, bond angles and hydrogen bonding for the structure are studied also.The structure analysis shows that the 3D-supramolecular architecture of 1 is stabilized by means six-(S6) intramolecular and eight-(R22(8)) membered intermolecular hydrogen bonds, together with extensive C—H…O and C—H…π interactions between the carboxylate anion and the 2-aminobenzimidazolium cation. Furthermore, parameters derived from density functional theory in a local sense, in particular the softness and Fukui function were used to interpret and predict the mechanism of the reaction.

Development of Tizanidine Drug-in-Adhesive Patch: Molecular Mechanism of Permeation Enhancer on Regulating Miscibility and Drug Release by Affecting the Status of Ion-Pair in Polymer Matrix

The objective of this work was to develop a drug-in-adhesive (DIA) patch of TIZ by employing ion-pair and permeation enhancer to increase drug-polymer miscibility and drug release. Special attention was paid on the regulation effect of permeation enhancer on ion-pair status in pressure sensitive adhesives (PSA). Formulation factors including TIZ-fatty acids ion-pair, drug loading and permeation enhancer were investigated by ex-vivo transdermal experiments. Optimized patch was evaluated by pharmacokinetics study. The better polarity similarity and strong hydrogen bonding interactions between TIZ-caproic acid ion-pair (TIZ-C6) and PSA was confirmed by polarity determination, FT-IR, TOPEM of MDSC and theoretical calculation, which determined enhanced miscibility of ion-pair and PSA. The permeation enhancer affected status of ion-pair in PSA by regulating polarity similarity and interaction between ion-pair and PSA, resulting in increased drug-PSA miscibility and drug release, which was characterized by FT-IR, polarity determination, thermal analysis and molecular dynamics simulation. The optimized patch showed high drug-polymer miscibility and drug skin permeability with AUC0-t of 14641.12 ± 854.45 h ng/mL and Cmax of 834.55 ± 155.68 ng/mL, which was significantly higher than the control group. In conclusion, DIA patch of TIZ was prepared and it supplied a reference for design of DIA patches with TIZ.

Enhanced in vitro antitumor efficacy of a polyunsaturated fatty acid-conjugated pH-responsive self-assembled ion-pairing liposome-encapsulated prodrug

The development of clinical chemotherapeutics is always challenging due to the toxicity and side effects of drugs not only for tumor cells but also for normal cells. Therefore, nano-drug delivery systems and prodrug strategies have been applied to address this challenge. Herein, we report a liposome-encapsulated small-molecule prodrug nanosystem, self-assembled by doxorubicin (DOX) and mixed polyunsaturated fatty acid (MPUFA) ion-pairing (MPUFAs-DOX@Liposomes), which has a high omega-3 PUFA content. The increased lipophilicity of ion-paired MPUFAs-DOX can significantly improve the drug loading efficiency (∼97%). Electrostatic interaction, the hydrophobic effect and hydrogen bonding between the ion-pairing agents led to superior pH-responsive release of DOX from liposomes over DOX-loaded liposomes (DOX@Liposomes), with a more rapid release rate at pH 5.0 than at pH 7.4, which is beneficial for decreasing the toxicity of DOX under physiological conditions. Finally, the in vitro antitumor effects were investigated for two tumor cell types, A549 and MCF-7, and the results demonstrated that MPUFAs-DOX@Liposomes showed the highest cytotoxicity compared with free DOX and DOX@Liposomes because of the ready uptake under the effect of PUFAs. Hence, liposomes loaded with ion-paired MPUFAs-DOX is a promising formulation for combination cancer therapy.

Development of membrane electrodes for selective determination of lisinopril in pharmaceuticals

BackgroundLisinopril (LNP) is an angiotensin-converting enzyme inhibitor used as anti-hypertensive, cardiovascular, in anti-prophylactic and anti-diabetic nephropathy drug. Development of two new, simple, low cost, and selective membrane-based ion-selective electrodes has been proposed for the determination of LNP in pharmaceuticals.MethodsThe electrodes are based on poly(vinyl)chloride membrane doped with LNP-phosphotungstic acid (LNP-PTA) and LNP-phosphomolybdic acid (LNP-PMA) ion-pairs as molecular recognition materials.ResultsThe developed LNP-PTA and LNP-PMA electrodes are applicable for the determination of LNP over the linear range of 5 × 10−5–2.4 × 10−3 mol l−1. The working pH ranges to measure potentials were 2.5 to 6.4 and 2.3 to 6.0 for LNP-PTA and LNP-PMA ISEs, respectively. The electrodes displayed the rapid Nernstian responses as revealed by the values of slopes 55.06 and 52.39 mV/decade, with limit of detection (LOD) values of 1.2 × 10−5 and 1.18 × 10−5 mol l−1 for LNP-PTA and LNP-PMA electrodes, respectively. The limits of quantitation (LOQ) values have also been calculated for both the electrodes. The developed electrodes have potential stability for up to 1 month and emerged as highly selective for the determination of LNP over other spiked ions and compounds.ConclusionsThe proposed electrodes have been validated and found that they are suitable for the determination of LNP in pharmaceuticals in pure form and in dosage forms. The results obtained in the analysis of LNP using proposed electrodes have been compared statistically with reference method’s results to assess the accuracy and precision. Robustness and ruggedness of the developed electrodes have also been checked and found satisfactory. The recovery studies have been performed by standard addition procedure to assess the role of excipients in tablets containing LNP and the results obtained are satisfactory.

Electrochemical performance of screen printed sensors for potentiometric determination of anticholinergic oxybutynine hydrochloride in pharmaceutical formulations and biological fluids.

New potentiometric sensitive and selective modified screen printed electrodes (MSPE) which based on phosphotungestic acid (PTA), sodium tetraphenyl borate (NaTPB), phosphomolybdic acid (PMA) or ammonium reineckate (RN) ion pairing agents for determination of oxybutynine hydrochloride (OBCH) were developed. The proposed electrodes have Nernstian slope values of 59.20±0.52, 58.00±0.22 and 58.52±0.22 mV decade-1 for electrodes modified with 7.5, 17.5 and 7.5 mg of RN (electrode I), NaTPB (electrode II) and PTA (electrode III) ion pairing agents, respectively. It is found that the dynamic drug concentration range at 25 (C was 1.0x10-5 - 1.0x10-2 mole L-1 with detection limit (LOD) equal 1.0× 10-5 mol L-1 and limit of quantification (LOQ) equal 3.33×10-5 mol L-1. The response of MSPEs was pH independent in the range 2.0-6.0. The investigated electrodes have fast response time of 10, 9 and 8 s for electrodes I, II and III, respectively. These electrodes have good Nernstian response in the temperature range 10–60 °C. The slope of the straight–line obtained represented the isothermal coefficient of MSPEs which were found to be 1.594 ×10-3, 2.151×10-3 and 2.377×10-3 V/ for electrodes I, II and III, respectively. The small values of the isothermal coefficient indicated the high thermal stability of the electrodes. The MSPEs showed a relatively long life time of 36 days. Pure, biological fluids and pharmaceutical formulation of OBCH were quantified using calibration and standard addition methods and the obtained results agreed with that of the official HPLC method. Validation parameters were optimized according to ICH recommendations.