DOSY NMR, a new tool for fake drug analyses

Articles

01 Jun 2009

Stéphane Balayssac,^a Véronique Gilard,^a Marc-André Delsuc^b and Myriam Malet-Martino^a

^aUniversité de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB), Groupe de RMN Biomédicale, 118 route de Narbonne, 31062 Toulouse cedex 9, France
^bInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP 10142, 67404 Illkirch, France

Introduction

The capability of nuclear magnetic resonance (NMR) spectroscopy to provide valuable information regarding mixture analysis has created broad applicability in chemistry, biochemistry, biology and medicine. As drugs can be considered to be complex mixtures (composed of many different substances and/or including simultaneously high and very low quantities of compounds), NMR is a good tool for studying such formulations. Unfortunately, NMR has traditionally been sensitivity-limited compared with many other analytical techniques. Nevertheless, technological advancements in the field of magnetic resonance have made significant strides in improving sensitivity levels, developing new acquisition/processing tools and implementing innovative NMR experiments/pulse sequences.

For a long time it has been preferred, when possible, to isolate each mixture component prior to its study by NMR rather than to analyse the whole mixture. For most scientists, the preferred methods for mixture analysis and/or trace detection are still the chromatographic methods, generally coupled with spectroscopic methods such as mass spectrometry or NMR. LC-NMR, in which the NMR spectrometer acts as a high performance liquid chromatography (HPLC) detector, has been developed on this basis. But there is indeed “a pure NMR” method that allows a precise analysis of a complex mixture without any prior separation of the different components: the Diffusion Ordered SpectroscopY (DOSY) method.1 Furthermore, DOSY experiments do not need complicated setups and the method can be easily standardised and automated. One should also keep in mind the non-destructive nature of NMR spectroscopy.

The DOSY method allows measuring the translational self-diffusion of molecules in a solution. Based on the analysis of mono- and multi-exponential decays, spectra of mixture components can be separated depending on the value of their apparent diffusion coefficients. Diffusion measurement by NMR and especially the DOSY-type experiments are thus powerful analytical tools, which have so far been overlooked by most scientists.

This article outlines the use of the DOSY NMR method applied to drug analysis and screening for counterfeit drugs or fake herbal medicines.

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