HPLC Separation of Acetaminophen and its Impurities Using A Mixed-mode Reversed-Phase/Cation Exchange Stationary Phase

• Published in: Journal of chromatographic science Vol. 50; no. 4; pp. 335 - 342
• Main Authors: Călinescu, Octavian, Badea, Irinel A., Vlădescu, Luminiţa, Meltzer, Viorica, Pincu, Elena
• Format: Journal Article
• Language: English
• Published: Niles, IL Oxford University Press 01.04.2012; Preston Publications
• Subjects: Acetaminophen - analysis; Acetaminophen - isolation & purification; Acetanilides - analysis; Acetanilides - isolation & purification; Analysis; Asymmetry; Benzoquinones - analysis; Benzoquinones - isolation & purification; Biological and medical sciences; Buffers; Cation exchanging; Cations; Chromatography; Chromatography, High Pressure Liquid - methods; Chromatography, Ion Exchange - instrumentation; Chromatography, Reverse-Phase - instrumentation; Drug Contamination; Exchange; General pharmacology; Impurities; Limit of Detection; Linear Models; Medical sciences; Methyl alcohol; Pharmacology. Drug treatments; Phenols - analysis; Phenols - isolation & purification; Reproducibility of Results; Separation; Tablets; Thermodynamics; Validation; Fluorescence detector; Chemical analysis; Impurity; Antimigrainous agent; HPLC chromatography; Purity control; Oral form; Reversed phase chromatography; Paracetamol; Analgesic; Ultraviolet detector; Quality control; Antipyretic; Dosage form; Tablet; Mixed adsorbent; Cation exchanger; Quantitative analysis
• ISSN: 0021-9665; 1945-239X
• DOI: 10.1093/chromsci/bmr043

Determination of acetaminophen and its main impurities: 4-nitrophenol, 4'-chloroacetanilide, as well as 4-aminophenol and its degradation products, p-benzoquinone and hydroquinone has been developed and validated by a new high-performance liquid chromatography method. Chromatographic separation has been obtained on a Hypersil Duet C18/SCX column, using gradient elution, with a mixture of phosphate buffer (pH = 4.88) and methanol as a mobile phase. Analysis time did not exceed 14.5 min and good resolutions, peak shapes and asymmetries have resulted. The linearity of the method has been tested in the range of 5.0-60 µg/mL for acetaminophen and 0.5-6 µg/mL for the other compounds. The limits of detection and quantification have been also established to be lower than 0.1 µg/mL and 0.5 µg/mL, respectively. The method has been successfully applied for the analysis of commercial acetaminophen preparations.