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

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