High performance liquid impurity identification

J. Ogorka, G. Schwinger, G. Bmat and V. Seidel, On-line coupled reversed-phase high-performance liquid cliromatography-gas chromatography-mass specti ometi y , A powerful tool for the identification of unknown impurities in pharmaceutical products , J. Chromatogr. 626 87-96 (1992). 

G. Chevalier, P. Rohrbath, C. Bollet, and M. Caude, Identification and quantitation of impurities from Benorilate (Salipran) by high-performance liquid chromatography, J. Chromatogr. 138 (1977), 193-201. 

G. J. Lehr, T. L. Barry, G. Petzinger, G. M. Hanna, S. W. Zito, Isolation and identification of process impurities in trimethoprim drug substance by high-performance liquid chromatography, atmospheric pressure chemical ionization liquid chro-matography/mass spectrometry and nuclear magnetic resonance spectroscopy, J. Pharm. Biomed. Anal. 19 (1999), 373-389. 

Many of the most important chemical questions in the pharmaceutical industry involve the analysis of complex mixtures. Identification of low-level metabolites and drug substance impurities usually requires high-performance liquid chromatography for the separation of these mixtures or isolation of a compound of interest from a sample matrix. In these analyses, the structural information obtainable for the low-level compounds is limited by the type of detection used. The coupling of HPLC and mass spectrometry has become routine and provides useful molecular weight and fragmentation information, but this is often not enough for complete structure elucidation. 

The increasing need for identification of low-level (0.1%) impurities has lead to the development of specific methods for microgram amounts of analyte and for mixture analysis, and now key among these methods is the hyphenation of NMR to separation techniques such as high performance liquid chromatography (HPLC). LC/NMR is now such a widespread technique that a separate section is devoted to this topic. 

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