Detection of paracetamol binding to albumin in blood serum using 2D-IR spectroscopy

Rutherford, Samantha H. and Greetham, Gregory M. and Towrie, Michael and Parker, Anthony W. and Kharratian, Soheila and Krauss, Thomas F. and Nordon, Alison and Baker, Matthew J. and Hunt, Neil T. (2022) Detection of paracetamol binding to albumin in blood serum using 2D-IR spectroscopy. Analyst, 147 (15). pp. 3464-3469. ISSN 0003-2654 (

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Binding of drugs to blood serum proteins can influence both therapeutic efficacy and toxicity. The ability to measure the concentrations of protein-bound drug molecules quickly and with limited sample preparation could therefore have considerable benefits in biomedical and pharmaceutical applications. Vibrational spectroscopies provide data quickly but are hampered by complex, overlapping protein amide I band profiles and water absorption. Here, we show that two-dimensional infrared (2D-IR) spectroscopy can achieve rapid detection and quantification of paracetamol binding to serum albumin in blood serum at physiologically-relevant levels with no additional sample processing. By measuring changes to the amide I band of serum albumin caused by structural and dynamic impacts of paracetamol binding we show that drug concentrations as low as 7 μM can be detected and that the availability of albumin for paracetamol binding is less than 20% in serum samples, allowing identification of paracetamol levels consistent with a patient overdose.