engleski

Hyphenated LC-NMR method for characterization of drugs and bioactive molecules

To identify and structurally characterize impurities in drugs and bioactive molecules has become one of the primary goals of analytical chemists in modern pharmaceutical research. The FDA and other regulatory agencies require identification of all impurities in final drug products present above 0.1% level. Therefore, efficient, sensitive and reliable tools are needed to enable a comprehensive structural characterization of drug impurities in shorter time possible. Interfacing liquid chromatography with NMR spectroscopy and/or mass spectrometry provides a sophisticated and powerful approach to solve problems involving purity issues, degradation products or metabolism in drug discovery and development. More recently, on-line coupling of a solid phase extraction platform into LC-NMR or LC-NMR-MS systems and introduction of cryo-technology have drastically improved the sensitivity and it is now possible to perform two-dimensional hetero-nuclear LC-NMR experiments, such as HSQC or HMBC in a short time even for very low concentrated samples. This has significantly enhanced the ability to solve structural problems on-line. By using LC-NMR tedious and demanding preparative steps can be avoided which in turn significantly reduce the experimental time in many cases. The utility of LC-NMR, LC-SPE-NMR and LC-MS in identification and structure elucidation of drug impurities and degradation products will be demonstrated with selected examples.

LC-NMR; LC-MS; analysis; drug impurities

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