Using the response surface method for the spectrophotometric determination of 4-aminophenol in drugs

R.F. Bakeeva^*, S.Yu. Garmonov^**, A.A. Karimullina^***, V.F. Sopin^****

Kazan National Research Technological University, Kazan, 420015 Russia

E-mail: ^*gurf71@mail.ru, ^**serggar@mail.ru, ^***karimullina_30@mail.ru, ^****vlad_sopin24@rambler.ru

Received July 25, 2022

ORIGINAL ARTICLE

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DOI: 10.26907/2542-064X.2022.3.367-377

For citation: Bakeeva R.F., Garmonov S.Yu., Karimullina A.A., Sopin V.F. Using the response surface method for the spectrophotometric determination of 4-aminophenol in drugs. Uchenye Zapiski Kazanskogo Universiteta. Seriya Estestvennye Nauki, 2022, vol. 164, no. 3, pp. 367–377. doi: 10.26907/2542-064X.2022.3.367-377. (In Russian)

Abstract

4-Aminophenol (APh) is a toxic chemical that may be present as an impurity in drugs based on paracetamol, one of the main antipyretic analgesics. Thus, its content must be controlled to curb potential negative effects. Here, we explored the use of the response surface method and the three-level Box–Behnken designs to obtain an optimal premicellar matrix for the spectrophotometric determination of the APh impurities in drugs. For this purpose, the spectrochemical reaction of APh with 5,7-dichloro-4,6-dinitrobenzofuroxan (DCDNBF) was carried out, and the UV spectrum of the reaction product in the premicellar matrix composed of ethoxylated nonylphenol (neonol, APh 9-10) + dimethyl sulfoxide (DMSO) (20%) + Н₂О (80%) before and after the formation of micelles was analyzed. The response surfaces constructed with the help of the Statistica 10 software package turned out to be of prognostic value and were used to calculate the composition of the optimal matrix. An increase in the intensity of the absorption band in the premicellar region and a linear dependence in the concentration range of 5∙10^–7–2∙10^–4 mol/L APh were shown. The express and environmentally safe spectrophotometric method developed and tested in this study makes it possible to determine the APh content in dosage forms at the level of 0.0027%, which exceeds the maximum allowable one in paracetamol (no more than 0.01%).

Keywords: surfactants, neonol APh 9-10, spectrophotometry, 4-aminophenol, 5,7-dichloro-4,6-dinitrobenzofuroxan, response surface method, Box–Behnken designs, drugs

Figure Captions

Fig. 1. Structures of the compounds studied.

Fig. 2. Pareto diagram of the standardized effects produced by independent factors on the intensity of the А₄₃₀ absorption band. Effects with the significance level p < 0.05 were considered. X₁ – DCDNBFO concentration, X₂ – pH, X₃ – APh 9-10 concentration (L – linear effects, Q – quadratic effects).

Fig. 3. 3D plots showing the dependence of the А₄₃₀ absorption band on the concentration of the analytical reagent DCDNBF (X₁) and the medium pH (X₂) at the APh 9-10 concentrations of 0.010 mmol/L (a) and 0.190 mmol/L (b) in the micellar system APh 9-10 + DMSO (20%) + H₂O (80%).

Fig. 4. 3D plots showing the dependence of the А₄₃₀ absorption band on the medium pH (X₂) and the APh 9-10 concentration (X₃) at the analytical reagent DCDNBF concentrations (X₁) of 0.050 mmol/L (a) and 0.350 mmol/L (b) in the micellar system APh 9-10 + DMSO (20%) + H₂O (80%).

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