Comparison of Microflow and Analytical Flow Liquid Chromatography Coupled to Mass Spectrometry Global Metabolomics Methods Using a Urea Cycle Disorder Mouse Model.

Microscale-based separations are increasingly being applied in the field of metabolomics for the analysis of small-molecule metabolites. These methods have the potential to provide improved sensitivity, less solvent waste, and reduced sample-size requirements. Ion-pair free microflow-based global metabolomics methods, which we recently reported, were further compared to analytical flow ion-pairing reagent containing methods using a sample set from a urea cycle disorder (UCD) mouse model. Mouse urine and brain homogenate samples representing healthy, diseased, and disease-treated animals were analyzed by both methods. Data processing was performed using univariate and multivariate techniques followed by analyte trend analysis. The microflow methods performed comparably to the analytical flow ion-pairing methods with the ability to separate the three sample groups when analyzed by partial least-squares analysis. The number of detected metabolic features present after each data processing step was similar between the microflow-based methods and the ion-pairing methods in the negative ionization mode. The observed analyte trend and coverage of known UCD biomarkers were the same for both evaluated approaches. The 12.5-fold reduction in sample injection volume required for the microflow-based separations highlights the potential of this method to support studies with sample-size limitations.

A systematic approach to development of analytical scale and microflow-based liquid chromatography coupled to mass spectrometry metabolomics methods to support drug discovery and development.

As the reliance on metabolic biomarkers within drug discovery and development increases, there is also an increased demand for global metabolomics methods to provide broad metabolome coverage and sensitivity towards differences in metabolite expression and reproducibility. A systematic approach is necessary for the development, and evaluation, of metabolomics methods using either conventional techniques or when establishing new methods that allow for additional gains in sensitivity and a reduction in requirements for amounts of a biological sample, such as those seen with methods based on microseparations. We developed a novel standard mixture and used a systematic approach for the development and optimization of optimal, ion-pair free, liquid chromatography-mass spectrometry (LC-MS) global profiling methods. These methods were scaled-down to microflow-based LC separations and compared with analytical flow ion-pairing reagent containing methods. Average peak volume improvements of 7- and 22-fold were observed in the positive and negative ionization mode microflow methods as compared to the ion-pairing reagent analytical flow methods, respectively. The linear range of the newly developed microflow methods showed up to a 10-fold increase in the lower limit of detection in the negative ionization mode. The developed microflow LC-MS methods were further evaluated using wild-type mouse plasma where up to a 9-fold increase in peak volume was observed.

An advanced practice psychiatric nurse's guide to professional writing.

TOPIC: Many good ideas are not communicated to the community of mental health practitioners because advanced practice psychiatric nurses (APPNs) are not being well informed about writing for public dissemination. PURPOSE: This study aims to support APPNs through the various stages of manuscript preparation so they can enlarge the scope of their written contributions to the mental health field. CONCLUSIONS: An appreciation for the skills, mechanics, and attitudes that support the authoring enterprise can result in APPNs enjoying the multiple benefits that accrue to those who write about their professional activities for clinical, administrative, advocacy, fund-raising, and other purposes.

Screening offenders with histories of mental illness and violence for supportive housing.

This article describes a community mental health agency's process of screening supportive housing applicants with histories of violent felonies and serious mental illness. The agency adopted its corporate intranet as a tool so that geographically dispersed senior staff could participate in information gathering in order to ensure expert input in admissions decisions. This broad-based participation was designed to maintain community safety, while making the agency's residential resources available to people with mental illness and criminal histories. Considering the high recidivism rate of ex-offenders with mental illness and lack of clearly established best practices to serve them in the community, the authors believe that it is timely for housing providers to reevaluate how to better serve these individuals.

Lead optimization attrition analysis (LOAA): a novel and general methodology for medicinal chemistry.

Herein, we report a novel and general method, lead optimization attrition analysis (LOAA), to benchmark two distinct small-molecule lead series using a relatively unbiased, simple technique and commercially available software. We illustrate this approach with data collected during lead optimization of two independent oncology programs as a case study. Easily generated graphics and attrition curves enabled us to calibrate progress and support go/no go decisions on each program. We believe that this data-driven technique could be used broadly by medicinal chemists and management to guide strategic decisions during drug discovery.

Modeling and prediction of cocrystal phase diagrams.

In this paper, a new approach to model cocrystal phase diagrams is presented. Starting from an initial set of data, the phase diagram is obtained from discontinuous isoperibolic thermal analysis (DITA) and basic thermodynamic data (enthalpies and solubilities). The solubility product constant may then be determined. Since this constant is solvent independent, extrapolation to other solvents is possible. Application of this technique to an active pharmaceutical ingredient and glutaric acid demonstrates good agreement between calculated and experimental data.