Simultaneous Determination of Paracetamol, Propyphenazone and Caffeine in Presence of Paracetamol Impurities Using Dual-Mode Gradient HPLC and TLC Densitometry Methods

Abstract Two chromatographic methods were validated for the determination of the widely prescribed analgesic and antipyretic drug combination of paracetamol (PC) (recently integrated into the supportive treatment of COVID-19), propyphenazone (PZ) and caffeine (CF) in the presence of two PC impurities, namely 4-aminophenol and 4-nitrophenol. A “dual-mode” gradient high-performance liquid chromatography method was developed, where the separation was achieved via “dual-mode” gradient by changing both the ternary mobile phase composition (acetonitrile: methanol: water) and the flow rate. This enables a good resolution within a relatively shorter analysis time. The analysis was realized using Zorbax Eclipse XDB column C18, 5 μm (250 × 4.6 mm) and the UV detector was set at 220 nm. The other method is a thin-layer chromatography densitometry method, where the separation was achieved using a mobile phase composed of chloroform: toluene: ethyl acetate: methanol: acetic acid (6: 6: 1: 2: 0.1, by volume). Densitometric detection was performed at 220 nm on silica gel 60 F254 plates. The developed methods were fully validated as per the ICH guidelines and proved to be accurate, robust, specific and suitable for application as purity indicating methods for routine analysis of PC in pure form or in pharmaceuticals with PZ and CF in quality control laboratories.

[1]  A. Paladini,et al.  COVID-19 and NSAIDS: A Narrative Review of Knowns and Unknowns , 2020, Pain and Therapy.

[2]  G. Casalino,et al.  Coronavirus disease 2019 presenting with conjunctivitis as the first symptom , 2020, Eye.

[3]  P. Frawley,et al.  Thermodynamic properties of paracetamol impurities 4-nitrophenol and 4′-chloroacetanilide and the impact of such impurities on the crystallisation of paracetamol from solution , 2019, The Journal of Chemical Thermodynamics.

[4]  M. Abdelkawy,et al.  Enhancing prediction power of chemometric models through manipulation of the fed spectrophotometric data: A comparative study. , 2016, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[5]  Alison Brayfield,et al.  Martindale : the complete drug reference , 2014 .

[6]  A. Hałka-Grysińska,et al.  Simultaneous determination of acetaminophen, propyphenazone and caffeine in cefalgin preparation by pressurized planar electrochromatography and high-performance thin-layer chromatography , 2012 .

[7]  J. W. Coym Evaluation of ternary mobile phases for reversed-phase liquid chromatography: effect of composition on retention mechanism. , 2010, Journal of chromatography. A.

[8]  P. Jankovics,et al.  Determination of paracetamol and its main impurity 4-aminophenol in analgesic preparations by micellar electrokinetic chromatography. , 2008, Journal of pharmaceutical and biomedical analysis.

[9]  Y. Heyden,et al.  Validation of a fluorimetric assay for 4-aminophenol in paracetamol formulations. , 2008, Talanta.

[10]  François Couderc,et al.  Determination of non-steroidal anti-inflammatory drugs in pharmaceuticals and human serum by dual-mode gradient HPLC and fluorescence detection. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[11]  N. Ozaltin,et al.  Simultaneous determination of paracetamol, caffeine and propyphenazone in ternary mixtures by micellar electrokinetic capillary chromatography. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[12]  David B. Troy Remington : the science and practice of pharmacy , 2006 .

[13]  M. Özgür,et al.  A Rapid Spectrophotometric Method to Resolve Ternary Mixtures of Propyphenazone, Caffeine, and Acetaminophen in Tablets , 2002 .

[14]  E. Dinç,et al.  Derivative ratio spectra-zero crossing spectrophotometry and LC method applied to the quantitative determination of paracetamol, propyphenazone and caffeine in ternary mixtures. , 2001, Journal of pharmaceutical and biomedical analysis.

[15]  M. Medenica,et al.  The Second-Derivative Spectrophotometric Assay of a Multicomponent Analgetic Mixture , 2000 .

[16]  H. Tománková,et al.  [Densitometric determination of propyphenazone, paracetamol, guaiacol glycerol ether, caffeine and acetylsalicylic acid in analgesic-antipyretic preparations with thin-layer chromatography]. , 1989, Die Pharmazie.

[17]  J. Avramova Simultaneous determination of propyphenazone, paracetamol and caffeine in blood by high-performance liquid chromatography. , 1989, Journal of pharmaceutical and biomedical analysis.

[18]  M. G. Mamolo,et al.  Simultaneous quantitation of paracetamol, caffeine and propyphenazone by high-pressure liquid chromatography. , 1985, Journal of Pharmaceutical and Biomedical Analysis.