Abstract
The combination of high-performance liquid chromatography and mass spectrometry (LC/MS) has had a sign cant impact on drug development over the past decade. Continual improvements in LC/MS interface technologies combined with powerful features for structure analysis, qualitative and quantitative,have resulted in a widened scope of application. These improvements coincided with breakthroughs in combinatorial chemistry, molecular biology, and an overall industry trend of accelerated development.The use of high-performance liquid chromatographycombined with mass spectrometry (HPLC–MS) or tandem mass spectrometry (HPLC–MS–MS) has proven to be the analytical technique of choice for most assays used in various stages of new drug discovery. Asummary of the key components of HPLC–MS systems, as well as an overview of major application areas that use this technique as part of the drug discovery process, will be described here. This review will also provide an introduction into the various types of mass spectrometers that can be selected for the multiple tasks that can be performed using LC–MS as the analytical tool. The strategies for optimizing the use of this technique and also the potential problems and how to avoid them will be highlighted .
Highlights
Current trends in drug development emphasize high volume approaches to accelerate lead candidate generation and evaluation
The impact on the overall drug development cycle has been sign cant, creating unprecedented opportunities for growth and focus, in the analytical sciences The use of highperformance liquid chromatography combined with mass spectrometry (HPLC–MS) or tandem mass spectrometry (HPLC–MS–MS) has proven to be the analytical technique of choice for most assays used in various stages of new drug discovery 1.New drug discovery can be defined as the process whereby compound libraries are screened, hits are selected and modified to become leads that are optimized until a compound emerges that can be developed into a drug candidate
Various physical and chemical properties of these new chemical entities (NCEs) are assessed and HPLC–MS is often used for these assays
Summary
Current trends in drug development emphasize high volume approaches to accelerate lead candidate generation and evaluation. The impact on the overall drug development cycle has been sign cant, creating unprecedented opportunities for growth and focus, in the analytical sciences The use of highperformance liquid chromatography combined with mass spectrometry (HPLC–MS) or tandem mass spectrometry (HPLC–MS–MS) has proven to be the analytical technique of choice for most assays used in various stages of new drug discovery 1.New drug discovery can be defined as the process whereby compound libraries are screened, hits are selected and modified to become leads that are optimized until a compound emerges that can be developed into a drug candidate. HPLC–MS and HPLC–MS–MS are used for the analysis of newly synthesized compounds that become part of a compound library. Various physical and chemical properties (e.g. physiological solubility, permeability and chemical stability) of these new chemical entities (NCEs) are assessed and HPLC–MS is often used for these assays
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