Abstract:
Introduction: The presence of impurities in pharmaceutical formulations has been a concern worldwide. Acetaminophen is a commonly used drug for its analgesic and antipyretic properties. We report here a novel method for the impurity profiling of intravenous acetaminophen formulations by head space gas chromatography. In addition, impurity profiling of oral acetaminophen tablets and capsules available on the Lebanese market and manufactured in Lebanon was not reported, as well.
Objective: The purpose of this study is to detect impurities present in intravenous and oral samples of acetaminophen on the Lebanese market and analyze the risks that these impurities pose to human health.
Methods: static headspace gas chromatography- mass spectrometry was utilized as one of the most suitable methods to detect organic volatile impurities. Samples for intravenous use where first lyophilized prior to analysis. A total of 25 samples were analyzed: 9 and 16 for intravenous and oral use, respectively. Toxicological review was performed on the detected impurities and the different risks associated were analyzed.
Results: of the 9 intravenous samples analyzed, 6 contained impurities. As for the oral samples, 9 out of 16 samples contained impurities. A total of 14 different impurities were detected: acetaldehyde, cyclomethicone 5, cyclomethicone 6, dibutyl phthalate, diethyl phthalate, diacetamate, ethanol, ethyl stearate, formic acid, glycidol, methyl carbamate, methyl hydrazine, methyl stearate, and triethylamine. Several of the detected impurities are highly nephrotoxic, hepatotoxic, neurotoxic, carcinogenic, and/or teratogenic.
Conclusion: In view of the toxicity of the detected impurities and the negative impact they carry on the quality of the formulation as well as on human health, it is of utmost importance for the concerned pharmaceutical industries to take appropriate measures to control the source of these impurities and abide by the guidelines set by the regulatory authorities all around the world. Regulatory authorities should also take the necessary measures to preserve the safety of treated patients.
