A new method for the microdetermination of Para-aminophenol in generic brands of paracetamol tablets

Abstract

In Nigeria, paracetamol is readily available in several retail outlets where the conditions of storage can be poor leading to elevated levels of para-aminophenol (PAP), which is known to be nephrotoxic and hepatotoxic. However, the routine analysis of PAP is mostly by chromatographic separation which requires expensive instrumentation not often available in developing countries. The objective of this research was to develop a sensitive colorimetric method for the quantification of PAP in paracetamol. The method was based on the diazo coupling reaction between diazotised PAP and chromotropic acid. Various reaction parameters critical for optimal detector response were optimized. The validation of the new method was done following the determination of parameters including repeatability, reproducibility and selectivity using current ICH guidelines. The new method was also applied to the assay of PAP in 14 paracetamol tablet samples. The calibration was linear between 0.0297 and 0.2229 mg/mL at 470 nm with limits of detection and quantification of 0.0061 and 0.0185 mg/mL, respectively. The recovery was in the range of 95.96 and 102.21 while intra-and inter-day precisions at three different concentrations did not exceed 4.03%. The new method was successfully applied to quantify PAP in paracetamol with percent content varying from 0.14 to 0.21%w/w. A simple and reliable method for the quantification of PAP has been developed and successfully employed to report, for the first time, the presence of the degradation product at levels beyond the allowable limits in paracetamol dosage forms in Nigeria.

Visible Spectrophotometric Determination of Furosemide in Dosage Forms Following its Hydrolysis and Diazo Coupling with Chromotropic Acid

“…4. Although this result slightly differs from the 1:1 stoichiometric ratio obtained in our previous studies with chromotropic acid (Adegbolagun et al, 2018;Adegoke et al, 2019), there exists sufficient proof that furosemide hydrolyses in hydrochloric acid to yield an anthranilic derivative with a free amino acid group (Cruz et al, 1979). The primary aromatic amine can therefore be converted to the diazonium salt in the presence of nitrous acid and subsequently react with the activated ring system of chromotropic acid to generate the coloured azo adduct in a 1:1 ratio (Scheme 1).…”

Stability of Paracetamol Instant Jelly for Reconstitution: Impact of Packaging, Temperature and Humidity

“…In a study conducted in Nigeria on paracetamol tablets that were obtained from the open markets, street vendors, and patent medicine stores, a higher content of para-aminophenol was found in samples. The storage and handling conditions in several retail outlets can be poor and far from the ideal recommendations of USP and BP, which state that paracetamol must be preserved in tight, light-resistant containers stored at room temperature and protected from moisture and heat [ 36 ]. Moreover, it has been reported that the shelf life of commercial paracetamol tablets decreases to 11.3% and 31.9% due to hydrolytic degradation to para-aminophenol following an increase in storage temperature from 25 to 37 °C at relative humidity of 75% and 100%, respectively [ 37 ].…”

Application of Chitosan-Based Molecularly Imprinted Polymer in Development of Electrochemical Sensor for p-Aminophenol Determination

“…Moreover, the presence of p-AP in paracetamol samples may not only be a cause of therapeutic failure, but also may pose a safety issue, since p-AP has been shown to be significantly more potent than paracetamol as a nephrotoxicant in animal models [18]. The general method for determining p-AP levels is by spectrophotometry [19,20], and a Flow Injection Analysis (FIA) technique with a developed UV detector [21]. Since p-AP is an electroactive compound, its determination will be more selective by electrochemical methods.…”