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 µg/mL at 470 nm with limits of detection and quantification of 0.0061 and 0.0185 µg/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.
Highlights
Paracetamol is a commonly used analgesic in single and combination preparations that are formulated in a wide range of dosage forms including tablets, syrups, soluble powder, suppositories and injectables
Unwholesome storage of the drug may result in para aminophenol (PAP), which is the main degradation product of paracetamol as well as the main impurity from its synthesis, being present at levels in excess of the allowed limits of 0.005% and 0.1% by weight in bulk powder and dosage forms, respectively (BP, 2013)
The objective of this study was to develop a simple, cost-effective colorimetric method that is sufficiently sensitive and accurate to serve as an alternative to official methods in the routine detection and quantification of PAP in generic brands of paracetamol available in the Nigerian market using chromotropic acid
Summary
Paracetamol (acetaminophen) is a commonly used analgesic in single and combination preparations that are formulated in a wide range of dosage forms including tablets, syrups, soluble powder, suppositories and injectables. Paracetamol has substantial antipyretic activity and is often included in both over-the-counter and prescription drug therapies for common ailments like malaria. It is a widely sought-after medication in Nigeria that is readily available in pharmacies and in patent medicine drug stores and supermarkets where the handling and conditions of storage can be far from ideal (Orisakwe, Orish, & Aka, 1994). While the presence of PAP in samples of paracetamol might be the cause of therapeutic failure and raises safety concerns as PAP has been shown to be significantly more potent than paracetamol as a nephrotoxicant in animal models (Newton, Kuo, Gemborys, Mudge, & Hook, 1982), so the toxicity potential of the degradant following prolonged consumption as is the practice in most third world settings portends danger over time. It has hepatotoxic (Fu, Chen, Ray, Nagasawa, & Williams, 2004) and teratogenic activities (Bishop, 2003)
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