Nuclear magnetic resonance drug structure determination

Nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research has been used primarily in a classical, organic chemistry framework. Typical studies have included (1) the structure elucidation of compounds [1,2], (2) investigating chirality of drug substances [3,4], (3) the determination of cellular metabolism [5,6], and (4) protein studies [7-9], to name but a few. From the development perspective, NMR is traditionally used again for structure elucidation, but also for analytical applications [10]. In each case, solution-phase NMR has been utilized. It seems ironic that although —90% of the pharmaceutical products on the market exist in the solid form, solid state NMR is in its infancy as applied to pharmaceutical problem solving and methods development. 

After s)mthesis it is important to determine the drug s exact chemical structure. This will involve a variety of techniques such as mass spectrometry, nuclear magnetic resonance (H and C ), infrared and ultraviolet/visible spectrophotometry along with elemental analysis. This will confirm the medicinal chemist s proposed... 

R542 N. J. Skelton and W. J. Chazin, Solution Structure Determination of Proteins by Nuclear Magnetic Resonance Spectroscopy , Drugs Pharm. Sci., 2000,101, 683... 

Besides amino acid analysis and elaborated mass spectroscopy techniques, many more analytical methods are applied to support the identity examinations of the protein drug, such as determination of the extinction coefficient, isoelectric point, and crystal structure, as well as recording the nuclear magnetic resonance (NMR) and circular dichroism (CD) spectra and determining the chromatographic profiles from HPLC-runs as well as from capillary and polyacrylamide gel electrophoresis (CE and PAGE, respectively). 

Phospholipid-stabilized intravenous emulsions have been widely used for parenteral nutrition and have also been introduced as drug carrier systems, especially for lipophilic compounds. The aim of the authors in the next papers we review here (50,51) was to consider in detail various mediods, c.g., PCS. nuclear magnetic resonance (NMR). transmission electron micnoscopiy (TEM). and small-angle x-ray diffraction studies (SAXS), to determine parameters related to the internal structure of the particle in a model intravenous emulsion stabilized by phospholipids. An emulsion with an extremely high fat load and a classical emulsifier was chosen. PCS measurements were used to derive a particle size distnbu-tion and this was then us ) to calculate the total oil droplet surface area. The result indicated that there should be an excess of surfactants of 150%. Such an excess was not confirmed by either NMR or SAXS measurements and the dis-... 

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