Lucinda H Cohen

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The use of a cassette incubation of probe substrates with human liver microsomes (HLM) - also known as the 'cocktail' approach - is becoming a widely accepted approach to determine the interaction of new chemical entities (NCEs) with cytochrome P450 enzymes (CYP450) in early drug discovery. This article describes two LC-MS/MS-based analytical methods used(More)
Stromal cell-derived factor 1α (SDF-1α) or CXCL12 is a small pro-inflammatory chemoattractant cytokine and a substrate of dipeptidyl peptidase IV (DPP-IV). Proteolytic cleavage by DPP-IV inactivates SDF-1α and attenuates its interaction with CXCR4, its cell surface receptor. To enable investigation of suppression of such inactivation with pharmacologic(More)
Bioanalysis invited a selection of leading researchers to express their views on automation in the bioanalytical laboratory. The topics discussed include the challenges that the modern bioanalyst faces when integrating automation into existing drug-development processes, the impact of automation and how they envision the modern bioanalytical laboratory(More)
An online extraction/mass spectrometry technique was evaluated for direct analysis of plasma samples. A simple user-friendly online extraction system that consists of two pumps, an autosampler, a six-port switching valve and a mass spectrometer is described. The system was controlled by the LC-MS software (Masslynx 3.5, Waters Corporation, Beverly, MA).(More)
A tandem mass spectrometry method combined with an ion-pair chromatographic separation after weak cation exchange solid phase sample extraction for epinephrine (E), norepinephrine (NE) and dopamine (DA) has been developed. Two surrogate matrixes for plasma and urine as well as stable isotope labeled internal standards were utilized for quantitation. The(More)
A fully automated protein precipitation technique for biological sample preparation has been developed for the quantitation of drugs in various biological matrixes. All liquid handling during sample preparation was automated using a Hamilton MicroLab Star Robotic workstation, which included the preparation of standards and controls from a Watson laboratory(More)
The experimental measurement of plasma protein binding is a useful in vitro Absorption Distribution Metabolism and Excretion(ADME) assay currently conducted in both screening and definitive early development candidate modes. The fraction unbound is utilized to calculate important pharmacokinetic (PK) parameters such as unbound clearance and unbound volume(More)
Merck consolidated discovery stage bioanalytical functions into the Department of Pharmacokinetics, Pharmacodynamics & Drug Metabolism in 2007. Since then procedures and equipment used to provide important quantitative data to project teams have been harmonized and in many cases standardized. This approach has enabled movement of work across the network of(More)
A method is presented that describes a reliable and practical procedure for quantitation of an analyte present at relatively high background levels in blank (untreated) biological matrixes. Using a "surrogate analyte" approach, an endogenous analyte was quantitated in a variety of biological matrixes containing both very low (<10 ng/mL) and high (>2000(More)