Organic Salts of Pharmaceutical Impurity p -Aminophenol

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 8; p. 1910
• Main Authors: Khandavilli, U B Rao, Keshavarz, Leila, Skořepová, Eliška, Steendam, René R E, Frawley, Patrick J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.04.2020; MDPI
• Subjects: 4-aminophenol or p-aminophenol; Acids; Aminophenol; Aminophenols - chemistry; Analgesics; Calorimetry; Crystal structure; Crystallization; Crystallography, X-Ray; Differential scanning calorimetry; Drug Contamination; Experiments; Impurities; impurity removal; Infrared analysis; Infrared spectroscopy; Models, Molecular; Molecular Structure; Organic Chemicals - chemistry; Organic salts; Oxalic acid; p-Aminophenol; Paracetamol; particle size; Pharmaceutical industry; Pharmaceutical Preparations - analysis; Pharmaceutical Preparations - chemistry; Pharmaceutical Preparations - standards; Pharmaceuticals; Powders; Salicylic acid; salt; Salts; Salts - chemistry; Single crystals; Tartaric acid; Thermogravimetric analysis; Toxicity; X ray powder diffraction; X-ray diffraction; 4-aminophenol or p-aminophenol; particle size; salt; paracetamol; impurity removal
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25081910

The presence of impurities can drastically affect the efficacy and safety of pharmaceutical entities. -Aminophenol (PAP) is one of the main impurities of paracetamol (PA) that can potentially show toxic effects such as maternal toxicity and nephrotoxicity. The removal of PAP from PA is challenging and difficult to achieve through regular crystallization approaches. In this regard, we report four new salts of PAP with salicylic acid (SA), oxalic acid (OX), l-tartaric acid (TA), and (1 )-(+)-10-camphorsulfonic acid (CSA). All the PAP salts were analyzed using single-crystal X-ray diffraction, powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. The presence of minute amounts of PAP in paracetamol solids gives a dark color to the product that was difficult to remove through crystallization. In our study, we found that the addition of small quantities of the aforementioned acids helps to remove PAP from PA during the filtration and washings. This shows that salt formation could be used to efficiently remove challenging impurities.