Developing Analytical Applications for Parahydrogen Hyperpolarization: Urinary Elimination Pharmacokinetics of Nicotine.

Abstract

Nuclear magnetic resonance spectroscopy (NMR) is a valuable analytical tool with applications in a vast array of research fields from chemistry and biology to medicine and beyond. NMR is renowned for its straightforward data interpretation and quantitative properties, making it attractive for pharmacokinetic applications, where drug metabolism pathways, concentrations, and kinetics need to be evaluated. However, pharmacologically active compounds and their metabolites in biofluids often appear in minute concentrations, well below the detection limit of NMR. Herein, we demonstrate how parahydrogen hyperpolarization overcomes this sensitivity barrier, allowing us to detect mid-nanomolar concentrations of a drug and a drug metabolite in a biofluid matrix. The performance of the method is demonstrated by monitoring nicotine and cotinine urinary elimination, reflected by their concentrations in urine during the onset and withdrawal from nicotine consumption. An NMR limit of detection of 0.1 μM and a limit of quantitation of 0.7 μM is achieved in a practical pharmacokinetics scenario where precise quantitative and qualitative analysis is desired.