Capillary Electrophoresis-High Resolution Mass Spectrometry for Measuring In Vivo Arginine Isotope Incorporation in Alzheimer's Disease Mouse Models.

Immune-based metabolic reprogramming of arginine utilization in the brain contributes to the neuronal pathology associated with Alzheimer's disease (AD). To enable our long-term goals of differentiation of AD mouse model genotypes, ages, and sexes based on activity of this pathway, we describe here the novel dosing (using uniformly labeled (CN) arginine) and analysis methods using capillary electrophoresis high-resolution accurate-mass mass spectrometry for isotope tracing of metabolic products of arginine. We developed a pseudoprimed infusion-dosing regimen, using repeated injections, to achieve a steady state of uniformly labeled arginine in 135-195 min post bolus dose.

Likelihood ratio statistics for gene set enrichment in Alzheimer's disease pathways.

Introduction: The study of Alzheimer's disease (AD) has revealed biological pathways with implications for disease neuropathology and pathophysiology. These pathway-level effects may also be mediated by individual characteristics or covariates such as age or sex. Evaluation of AD biological pathways in the context of interactions with these covariates is critical to the understanding of AD as well as the development of model systems used to study the disease.

Skyline for Small Molecules: A Unifying Software Package for Quantitative Metabolomics.

Vendor-independent software tools for quantification of small molecules and metabolites are lacking, especially for targeted analysis workflows. Skyline is a freely available, open-source software tool for targeted quantitative mass spectrometry method development and data processing with a 10 year history supporting six major instrument vendors. Designed initially for proteomics analysis, we describe the expansion of Skyline to data for small molecule analysis, including selected reaction monitoring, high-resolution mass spectrometry, and calibrated quantification.

Discovery and targeted monitoring of polychlorinated biphenyl metabolites in blood plasma using LC-TIMS-TOF MS.

In the present work, the potential for rapid, targeted analysis of hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) in diluted human blood plasma using liquid chromatography coupled with trapped ion mobility spectrometry and TOF high resolution mass spectrometry (LC-TIMS-TOF MS) was evaluated. Experimental OH-PCB collisional cross section (CCS) and gas-phase candidate structures (<3% error) are reported for the first time and used, in addition to the LC retention time and accurate /, as OH-PCB identification features in order to increase the detection selectivity. The proposed LC-TIMS-TOF MS workflow combines a "dilute-and-shoot" sample preparation strategy, a robust liquid chromatography step, a high-resolving power mobility separation (R ~ 150-250) and high-resolution mass spectrometry (R ~ 30-40k) for the separation, identification and quantification of common OH-PCB isomers with limits of detection comparable to traditional workflows (e.

Analysis of isomeric opioids in urine using LC-TIMS-TOF MS.

In the present work, a fast separation, identification and quantification workflow based on liquid chromatography coupled to trapped ion mobility in tandem with mass spectrometry (LC-TIMS-MS) is described for the analysis of common isomeric drugs of abuse and their metabolites in human urine. In particular, the analytical performance of LC-TIMS-MS is shown for identification based on retention time, collision cross section and accurate mass for three sets of common isomeric opioids and their deuterated analogs in urine. The LC-TIMS-MS analysis provided limits of detection of 1.

Lipid specific molecular ion emission as a function of the primary ion characteristics in TOF-SIMS.

In the present work, the emission characteristics of lipids as a function of the primary ion cluster size and energy were studied using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Characteristic fragmentation patterns for common lipids are described, and changes in secondary ion (SI) yields using various primary ion beams are reported. In particular, emission characteristics were studied for pairs of small polyatomic and nanoparticle primary ion beams (e.

Isomer Separation of Polybrominated Diphenyl Ether Metabolites using nanoESI-TIMS-MS.

In this paper, high-resolution nano-electrospray ionization-trapped ion mobility spectrometry coupled to mass spectrometry (nESI-TIMS-MS) is used for the study of hydroxylated polybrominated diphenyl ether (OH-PBDE) metabolites. In particular, experimental ion-neutral collision cross sections (CCS) were measured for five structural OH-PBDE isomers using TIMS-MS. Candidate structures were proposed for each IMS band observed in good agreement with the experimental CCS measurements (5% error).

DART-MS for rapid, preliminary screening of urine for DMAA.

Dimethylamylamine (DMAA) is a sympathomimetic amine found in weight-loss/workout supplements or used as an appetite suppressant. DMAA is a stimulant that is banned by the World Anti-Doping Agency (WADA). Adverse health effects as well as fatalities have been implicated with its use.