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Metabolic Stability Assay Using Human Hepatocyte Co-cultures and Integrated Qualitative/Quantitative High Resolution Mass Spectrometry
Alex Zang, Ragu Ramanathan, Cornelia Smith, Caroline Lee, Helen Shen, and Zamas Lam

Purpose: To investigate Sequential Window Acquisition of all Theoretical fragment ion spectra (SWATH™) based integrated qualitative and quantitative (qual/quant) assay for simultaneous metabolic stability and metabolite profiling assessments.

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In Vitro Species Comparison Using Long-Term Hepatocyte Co-Cultures Model and Highly Sensitive UHPLC-QTOF-MS with SWATH Analysis
Jian Yu; Ragu Ramanathan; Cornelia Smith; Caroline Lee; Helen Shen; Zamas Lam

Purpose: To develop a reliable, quicker, and cost-saving in vitro method to accurately predict major human metabolite profile in vivo and to de-risk disproportional or unique human metabolites before a drug candidate nomination

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Metabolite Profiling Using Human Hepatocyte Co-cultures and UHPLC-QTOF-MS with Data Independent MS/MS
Ronghua Wang, Ragu Ramanathan, Cornelia Smith, Caroline Lee, Helen Shen, and Zamas Lam

Purpose
To investigate a high throughput workflow for metabolite profiling using a novel human in vitro system and advanced UHPLC-MS/MS techniques to accurately predict human metabolite profile in vivo.

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TOXICITY OF SELECTED BIOACTIVATED COMPOUNDS IN PRIMARY RAT HEPATOCYTES CULTURED IN MICROPATTERNED CO-CULTURES
Okechukwu Ukairo, Julianne Shi, Justin Jackson, Kelly Rose, Melvin E. Andersen, and Edward L. LeCluyse

Drug Induced Liver Injury (DILI) modeled in a novel co-culture liver model. Here, we assess the bioactivation and cytotoxicity of acetaminophen (APAP) and other compounds in the 96-well rat MPCC.

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Mixtures Analysis of Complex Mixtures
Michael Bernstein; Carlos Cobas; Santi Domínguez; Manuel Pérez; Agustín Barba

We describe an NMR method to quantify mixture components in wine, edible oils, etc. The method is fully customizable, and amenable to high throughput operation.

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Comparison of Three Methods for the Evaluation of Cytokine Storm Risk in Early and Clinical Stage Biopharmaceutical Development
Gary dos Santos and Emer Clarke

Objective: To identify an assay that can accurately predict the risk of CRS and CS associated with investigational biotherapeutics. A comparison of three methods were used: (a) immobilization of test antibody on plastic, (b) co-culture of PBMC's on HUVEC's and (c) pre-culture of PBMC's at high cell density.

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Isolation, Identification, and Determination of Designer Anabolic Steroids Commonly Found in Dietary Supplements
Sarah E. Voelker, M.S.; Travis M. Falconer, Ph.D.; Jonathan J. Litzau; Mary B. Jones; Lisa M. Lorenz

A general analytical approach in identifying emerging steroid-like compounds is presented, including analysis by GC-MS, LC-MS, and/or HPLC-UV. Isolation of unknown compounds was achieved by high performance liquid chromatography with fraction collection. Isolated compounds were characterized by Nuclear Magnetic Resonance spectroscopy and high resolution accurate mass-mass spectrometry to elucidate their structure.

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A Mass Spectrometer for Elemental Analysis based on Fieldable Technologies
Hilary Brown, Jennifer Speer, John Gerling, and Kenyon Evans-Nguyen

Laser ablation and a Microwave Plasma Torch (MPT) were coupled in order to obtain elemental information from solid samples. The MPT was incorporated as a less costly and more portable alternative to the ICP. MPT was also added to help improve the signal from just the laser ablation alone.

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Combining low and high volume liquid handling capabilities for ADME screening
Joby Jenkins, Kevin Moore, Stephen Fowler, Pascal Schenk

In this study we demonstrate the integration of two liquid handlers to extend the volume dispensing range creating low-volume assay-ready plates with high accuracy and precision. This was then successfully applied to a CYP inhibition assay.

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Scientific News
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
Breakthrough Approach to Breast Cancer Treatment
Scripps scientists have designed a drug candidate that decreases growth of breast cancer cells.
Non-Toxic Approach to Treating Variety of Cancers
A team of researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine recently discovered a novel, non-toxic approach to treating a wide variety of cancers.
Making Injectable Medicine Safer
Researchers remove excess additives from drugs, which could reduce the odds of serious allergic reactions and other side effects.
An Old-New Weapon Against Emerging Chikungunya Virus
Researchers utilize existing drugs to interfere with host factors required for replication of Chikungunya virus.
Brazilian Zika Virus Strain Causes Birth Defects in Experimental Models
First direct experimental proof of causal effect, researchers say.
'Kidney on a Chip' Facilitates Safer Drug Dosing
University of Michigan researchers have used a "kidney on a chip" device to mimic the flow of medication through human kidneys and measure its effect on kidney cells.
Ketamine Metabolism Lifts Depression
NIH-funded team finds rapid-acting, non-addicting agent in mouse study.
Turning Skin Cells into Heart, Brain Cells
In a major breakthrough, scientists at the Gladstone Institutes transformed skin cells into heart cells and brain cells using a combination of chemicals.
Growing Stem Cells More Safely
Nurturing stem cells atop a bed of mouse cells works well, but is a non-starter for transplants to patients – Brown University scientists are developing a synthetic bed instead.
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