Current Topics in Medicinal Chemistry - Volume 2, Issue 1, 2002

Off-line miniaturized “nano-spray” formats for electrospray ionization mass spectrometry (ESI-MS) enable the routine identification of femtomole quantities of protein or peptide. Even greater strides have been achieved using on-line miniaturized ESI-MS methods, such as nanobore LC-MS and CE-MS. On-line methods enable greater sensitivity (sub-attomole limit of detection), dynamic range, and throughput. In either off- or on-l Read More

Electrospray ionization (ESI) and matrix-assisted laser desorption / ionization (MALDI) mass spectrometric methods useful for early discovery drug screening are reviewed. All methods described involve studies of non-covalent complexes between biopolymer receptors and small molecule ligands formed in the condensed phase. The complexes can be sprayed intact directly into the gas phase by ESI-MS using gentle experi Read More

Biofluid NMR spectroscopy is a powerful tool providing a comprehensive metabolic profile of the low molecular weight components in biofluids that reflect concentrations and fluxes of endogenous metabolites involved in key intermediary cellular pathways, thereby giving an indication of an organisms physiological or pathophysiological status [1]. The interaction of pharmacological agents with cells and tissues can also be mo Read More

LC / MS / MS based bioanalysis using atmospheric pressure ionization (API)-style interfaces has now been applied for over a decade. This technology, which initially found application for clinical bioanalysis, is now firmly established as the primary bioanalytical tool for ADME studies related to drug discovery and lead optimization (LO). This review focuses on recent advances in LC / MS / MS based bioanalysis in suppor Read More

The past years have seen only the beginning of our understanding of metabolic processes and the importance of these processes to the development of safe and effective medicines. The trend to bring more detailed information into earlier stages of drug discovery will continue to drive improvements in technology and in experimental and analytical procedures for the study of biotransformation of drugs. The challe Read More

Organ perfusion techniques bridge the methodological gap between in vivo studies on the one hand and in vitro studies on the other. In drug candidate selection and subsequent development the differences between these systems should be considered carefully in study design, as one approach may be more suitable than the other depending on the question(s) being asked and, in particular, how the data will be used.Th Read More

The field of pharmaceutical profiling in drug discovery is described. The pharmaceutical properties of drug candidates determine how much of the drug safely reaches the therapeutic target. Drug candidates often fail in discovery and development due to inadequate properties, resulting in lost opportunities and resources for developing new drugs. Pharmaceutical profiling assays have been developed and implemented to meas Read More

The rapid growth of mass spectrometry (MS)-based computer software applications has been fueled by the unprecedented need to capture and analyze MS data and provide the information necessary for decision-making. Shorter timelines and a significantly greater number of samples has resulted in a tremendous focus on streamlined approaches that provide scientists, managers, and executives the capability to readily ob Read More