EVALUATION OF PARAMETER-DEPENDENT CHANGES IN THE RESPONSE OF ION-SELECTIVE ELECTRODES FOR RAPID PHARMACEUTICAL DETECTION USING HETEROPOLY METAL PHOSPHATE IONOPHORES

ABSTRACT

The influence of various factors on the signal magnitude of ion-selective electrodes in the determination of pharmaceutical substances has been investigated. Dodecamolybdophosphate (DMP) and dodecatungstophosphate (DTP), which exhibit high sensitivity, were used as ionophores. The possibility of determining dibazole, pyridoxine, diprazine, and bromhexine within the temperature range of 10–50 °C and pH range of 4–7 has been established using ionophores based on DMP+drug and DTP+drug complexes.

АННОТАЦИЯ

 Изучено влияние различных факторов на значение сигнала ионоселективных электродов  при обнаружении лекарственных средств, в качестве ионофоров были выбраны додекомолибдофосфат (ДДМФ) и додевольфрамфосфат (ДДВФ) с высокой чувствительностью. Определена возможность обнаружения дибазола, пиридоксина, дипразина и бромгексина в диапазоне температур 10-50 ⁰С и диапазоне рН 4-7 в присутствии ионофоров, содержащих ДДМФ+препарат и ДДВФ+препарат.

Keywords: Ion-selective electrode, membrane, concentration, temperature, ionophore.

Ключевые слова: ионселективный электрод, мембрана, концентрация, температура, ионофоры.

Introduction. Due to the rapid development of the chemical and pharmaceutical industries, the demand for fast, accurate, and simple methods for the analysis of pharmaceutical substances is steadily increasing [1,2]. Existing expensive techniques—such as high-performance liquid chromatography, capillary electrophoresis, and others—require complex sample preparation and highly qualified personnel, which limits their applicability for large-scale drug analysis [3,4]. Therefore, the development of rapid, relatively simple, and cost-effective methods suitable for screening the composition of pharmaceutical formulations is of particular interest.Plasticized membrane ion-selective electrodes (ISEs) represent an effective solution to this problem [5,6]. Consequently, the creation of a new generation of active electrode materials and the development of selective electrodes based on them for the determination of pharmaceutical compounds are important tasks. One of the most significant parameters influencing the ISE response is the amount of components incorporated into the membrane composition [8].The aim of this study is to determine the optimal content of the ionophore in the membrane that ensures high sensitivity and selectivity, as well as to investigate the influence of various factors on the ISE signal

Materials and Methods.

The dependence of the signal magnitude of diprazine-detecting electrodes on the amount of ionophore incorporated into the membrane, within the range of 0.5–3.0%, was studied using pyridoxine. In the experiments, solutions of the detectable component with concentrations ranging from 10⁻² to 10⁻⁵ mol/L were used. All experiments were carried out at room temperature. The results of the study on the dependence of the developed signal of ion-selective electrodes (ISEs) on the ionophore content in the membrane are presented in Table 1.

Table 1.

Dependence of the signal generated by pyridoxine and diprazine ISEs on the amount of ionophore in the membrane (n = 5, p = 0.95).

Results of the Study on the Effect of Ionophore Concentration on ISE Signal

The effect of ionophore content in the membrane on the ion-selective electrode (ISE) signal during the determination of pyridoxine and diprazine was investigated.

The highest signal value (170.8 mV) for pyridoxine determination using an ISE containing pyridoxine dodecamolybdophosphate was observed at an ionophore concentration of 2.5% — [(C₁₈H₁₂NO₃)₃[P(Mo₁₂O₄₀)]]. For all the studied membranes, the dependence of the ISE signal on ionophore concentration exhibited a maximum-type relationship.The maximum signal (240 mV) during diprazine determination was recorded for an electrode whose membrane contained 2.0% of the ionophore [(C₁₇H₂₁N₂S)₃[P(W₁₂O₄₀)]]. After reaching the optimal concentration (2.0–2.5%), a further increase in ionophore content resulted in a decrease in the signal amplitude.

Thus, during the detection of pyridoxine and diprazine, the use of a gas-inert material containing the corresponding heteropoly metal phosphate compounds (dodecamolybdophosphate and dodecatungstophosphate) provides the maximum electrode response. The optimal ionophore content in the membrane is 2.5% for pyridoxine and 2.0% for diprazine.The results of the study indicate that at a 2% concentration of dodecamolybdophosphate ionophore in the membrane, pyridoxine shows the highest sensitivity for drug detection using heteropoly metal phosphate-based membranes.

Proceeding to the Next Experiments on Drug Detection

The following amounts of ionophoric compounds in the membrane were selected:

For the determination of pyridoxine hydrochloride — 2.5% (C₈H₁₂NO₃)₃[P(Mo₁₂O₄₀)] pyridoxine dodecamolybdophosphate.

For the determination of diprazine hydrochloride — 2.0% (C₁₇H₂₁N₂S)₃[P(W₁₂O₄₀)] diprazine dodecatungstophosphate.

The temperature dependence of drug-selective electrodes was studied in solutions of diprazine and pyridoxine with concentrations of 10⁻² mol/L and 10⁻³ mol/L. The effect of temperature on the ISE signal was investigated in the range of 10–50 °C, with a 5 °C increment.In the experiments, cooling of the solutions below 25 °C was carried out in a refrigerator, while heating above 25 °C was performed using a TS-80 type thermostat. All measurements were conducted under continuous stirring of the solution with a magnetic stirrer. Figure 1 shows the temperature dependence of the signal for different drug-selective electrodes.

Figure 1. Dependence of the signal magnitude of ion-selective electrodes based on dodecaphosphomolybdate and dodecaphosphotungstate on the solution temperature for the detection of pyridoxine (a) and diprazine (b).

Solution concentrations: 1 — 10⁻² mol/L; 2 — 10⁻³ mol/L.

As can be seen from the figure, the greatest deviation of the electrode signal from the value obtained under normal temperature conditions (at 25 °C) was observed during the detection of pyridoxine using the ion-selective electrode based on pyridoxine dodecaphosphomolybdate. However, when detecting diprazine and pyridoxine with ion-selective electrodes based on dodecaphosphotungstate and dodecaphosphomolybdate, the increase in temperature from 10 °C to 50 °C remained within the experimental error range of the electrode signal, with variations between 1.3 and 4.0 mV. Thus, the developed electrodes can be effectively used to detect diprazine and pyridoxine within the temperature range of 10–50 °C. One of the factors affecting the performance of ion-selective electrodes is the pH value of the test solution, i.e., the surrounding medium. The dependence of the signal magnitude of the developed drug-selective electrodes on the pH of the detecting medium was studied within the pH range of 3–10. In these experiments, solutions of diprazine hydrochloride and pyridoxine hydrochloride were used. The pH values of the solutions were varied from 3 to 10 in increments of one unit, while the concentration of the detected component remained constant at 10⁻² mol/L in all cases. All experiments were carried out by measuring the electrode potential at 25 °C.

Table 2 presents the results of determining the dependence of the electrode potential (E) on the pH of the solutions of various pharmaceutical compounds at a concentration of 10⁻² mol/L.

Table 2.

Influence of the solution medium on the sensor signal magnitude during the detection of various pharmaceutical compounds (n = 5, P = 0.95, C = 10⁻² mol/L)

From Table 2, it can be seen that it is possible to determine the pH of the solution medium using the ion-selective electrodes developed from the pharmaceutical compound solutions. The detection range of pyridoxine by ISEs based on an ionophore containing dodecamolybdophosphate + drug corresponds to a pH of 4–7. For ISEs based on an ionophore containing dodecatungstophosphate + drug, the detection range of diprazine also corresponds to a pH of 4–7. The electroanalytical performance of the ion-selective electrodes, developed using dodecamolybdophosphate and dodecatungstophosphate ionophores, was studied during the detection of pharmaceutical compounds. For the determination of the electrode function of the developed ISEs, solutions of pyridoxine and diprazine hydrochloride in the concentration range from 1×10⁻¹ to 1×10⁻⁷ M were used. For the study, six electrodes were prepared from each type of membrane. Figure 2 below shows the electrode functions during the detection of pyridoxine and diprazine hydrochloride using electrodes based on DDMF and DDWF ionophores.

Figure 2. Range of electrode function performance of ISEs based on heteropoly metal phosphate ionophores (Nernstian region).

 α — pyridoxine hydrochloride; β — diprazine hydrochloride

As can be seen from Figure 2, the operational range (Nernstian region) of the ISEs based on heteropoly metal phosphate ionophores for the detection of pyridoxine hydrochloride and diprazine hydrochloride corresponds to the concentration range of 1×10⁻¹ – 1×10⁻⁵ M.

Conclusions. The regularities revealed in the course of the study allowed for the selection of membrane compositions with the best electroanalytical properties and the development of ISEs for the quantitative determination of pyridoxine and diprazine hydrochloride. The developed ISEs provide high sensitivity for the detection of these pharmaceutical compounds within the temperature range of 10–50 °C. The main effects of pH on the electrode functions of pyridoxine- and diprazine-sensitive ISEs were identified and quantitatively evaluated. It was determined that the operational range of the electrode function of the developed ISEs (Nernstian region) corresponds to 1×10⁻¹ – 1×10⁻⁵ M.

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