Magnetic resonance spectroscopy: a powerful tool for drug metabolism studies

Assignment and pH dependence of the19F-NMR resonances from the fluorouracil anabolites involved in fluoropyrimidine chemotherapy

“…FdUMP was purchased as the Na salt from Sigma (F-3503). FUMP was synthesized as the NH 4 salt by F. Oberdorfer and K. Weber of the Department of Radio-chemistry and Radiopharmacology at the German Cancer Research Center according to published methods. 42 Model solution A.…”

“…Fluoropyrimidine metabolism [1][2][3] in humans and animals is an important aspect of clinical and experimental chemotherapies with the antitumor agent 5-fluorouracil (FUra, 5-FU) or its nucleosides such as 5-fluoro-2'deoxyuridine (FdUrd), and has been intensively studied using 19 F-NMR spectroscopy. 4,5 In clinical in vivo studies [6][7][8][9][10][11][12] usually the only signals which can be detected from the liver, for example, are from FUra, its final major catabolite a-fluoro-b-alanine (FBAL) and sometimes the catabolic precursors 5-fluoro-5,6-dihydrouracil (DHFU) and a-fluoro-b-ureidopropionic acid (FUPA). Following high-dose treatment it is possible in tumors or metastases to detect an unresolved signal band representing total anabolites, 8 i.e.…”

NMR techniques in biomedical and pharmaceutical analysis

“…However, NMR has also found many applications in other fields than chemistry, such as food science, biology, pharmacy and medicine since it is the only physical method used routinely that can provide quantitative valuable information at the molecular level, regarding analysis of complex mixtures from fluids of biological origin, food materials, beverages, drugs, cell or tissue extracts, excised tissues, cell pellets (in vitro studies) to isolated perfused biological systems (cell or organs) (ex vivo studies) [4][5][6][7][8][9][10][11][12][13][14][15] and finally intact living systems (bacteria, plants, animals and humans) (in vivo studies) [16][17][18][19][20].…”

Application of 19F NMR Spectroscopy for Content Determination of Fluorinated Pharmaceuticals

“…Furthermore, 19 F NMR has a broader chemical shift range (approx. 500 ppm) [10], which helps to avoid signal overlap and shows less interference from homonuclear coupling [11–13] and more importantly the solvent (mostly containing no fluorine) has no effect on the 19 F NMR signal and as such solvent suppression is not necessary. This makes the technique uniquely suitable for quantification of fluorine-containing compounds in various matrices including finished pharmaceutical products.…”