on 05-01-201210:40 AM - edited on 10-15-202111:34 AM by AnalyteGuru
Hatsis P, Kapron JT. Rapid Commun Mass Spectrom. 2008;22(5):735-8. Liquid chromatography coupled to mass spectrometry (LC/MS) using atmospheric pressure ionization has had a far-reaching and profound influence on the drug discovery and development process in the pharmaceutical industry. The speed, selectivity and sensitivity inherent to LC/MS, provide unparalleled solutions to complex analytical problems. LC/MS, however, is not without pitfalls. For instance, the sheer complexity of certain samples place stringent requirements on the analyst to develop a rugged and robust method for the quantification of the compound of interest. Successful LC/MS method development requires isolation of the analyte from the matrix. Sample preparation and chromatography can be time-consuming research projects, particularly when challenging problems arise, such as endogenous interferences or elevated chemical background. Mass spectrometry imparts an added dimension of selectivity and signal-to-noise improvement through fragmentation and high resolution. There are certain problems, however, such as compounds with isobaric interferences or compounds that fragment poorly, where mass spectrometry alone does not provide the needed selectivity to develop robust methods. In these instances, methods development would be greatly facilitated through the use of new orthogonal techniques.