Density-dependent winter survival of immatures in an irruptive raptor with pulsed breeding.

Highly mobile predators can show strong numerical responses to pulsed resources, sometimes resulting in irruptions where large numbers of young invade landscapes at a continental scale. High production of young in irruption years may have a strong influence on the population dynamics unless immature survival is reduced compared to non-irruption years. This could occur if subordinate individuals (mainly immatures) are forced into suboptimal habitats due to density-dependent effects in irruption years.

Retention characteristics of some antibiotic and anti-retroviral compounds in hydrophilic interaction chromatography using isocratic elution, and gradient elution with repeatable partial equilibration.

The separation of some zwitterionic, basic and neutral antibiotic and antiretroviral compounds was studied using hydrophilic interaction chromatography (HILIC) on bare silica, bonded amide and urea superficially porous phases. The differences in the selectivity and retentivity of these stationary phases were evaluated for compounds with widely different physicochemical properties (logD -3.43 to 2.

Application of machine learning in prediction of hydrotrope-enhanced solubilisation of indomethacin.

Systematic in-vitro studies have been conducted to determine the ability of a range of 10 potential hydrotropes to improve the apparent aqueous solubility of the poorly water soluble drug, indomethacin. Solubilisation of the drug in the presence of the hydrotropes was determined experimentally using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. These experimental data, together with various known and computed physicochemical properties of the hydrotropes were thereafter used in silico to train an artificial neural network (ANN) to allow for predictions of indomethacin solubilisation.

External Validation and Optimization of International Consensus Clinical Target Volumes for Adjuvant Radiation Therapy in Bladder Cancer.

Purpose: International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance.

Methods And Materials: Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review.

Development and application of sub-2-μm particle CO -based chromatography coupled to mass spectrometry for comprehensive analysis of lipids in cottonseed extracts.

Rationale: Refined cottonseed oil has widespread applications in the food and chemical industries. Although the major lipids comprising cottonseed oil (triacylglycerols) are well known, there are many diverse lipid species in cotton seeds that occur at much lower levels and have important nutritional or anti-nutritional properties.

Methods: The lipid technical samples were prepared in chloroform.

Analysis of polar urinary metabolites for metabolic phenotyping using supercritical fluid chromatography and mass spectrometry.

Supercritical fluid chromatography (SFC) is frequently used for the analysis and separation of non-polar metabolites, but remains relatively underutilised for the study of polar molecules, even those which pose difficulties with established reversed-phase (RP) or hydrophilic interaction liquid chromatographic (HILIC) methodologies. Here, we present a fast SFC-MS method for the analysis of medium and high-polarity (-7≤cLogP≤2) compounds, designed for implementation in a high-throughput metabonomics setting. Sixty polar analytes were first screened to identify those most suitable for inclusion in chromatographic test mixtures; then, a multi-dimensional method development study was conducted to determine the optimal choice of stationary phase, modifier additive and temperature for the separation of such analytes using SFC.

Pharmacokinetic variations in cancer patients with liver dysfunction: applications and challenges of pharmacometabolomics.

Purpose: In cancer patients, pharmacokinetic variations between individuals and within individuals due to impairments in organs' function and other reasons such as genetic polymorphisms represent a major problem in disease management, which can result in unpredictable toxicity and variable antineoplastic effects. Addressing pharmacokinetic variations in cancer patients with liver dysfunction and their implications on anticancer and analgesic drugs, in addition to the use of advanced analytical techniques such as metabolomics and pharmacometabolomics, to monitor altered kinetic and discover metabolic biomarkers during therapeutic intervention will help in understanding and reducing pharmacokinetic variations of drugs in cancer patients as a step forward towards personalised medicine.

Methods: Reviewing published literature addressing and/or related to complications resulting from altered pharmacokinetics (PKs) in cancer patients with liver dysfunction, anticancer and analgesic drugs, evaluating recent advances of pharmacokinetic detection using metabolomics/pharmacometabolomics and the challenges that are currently facing these techniques.

An integrated ceramic, micro-fluidic device for the LC/MS/MS analysis of pharmaceuticals in plasma.

An integrated capillary scale (300 μm id) ceramic microfluidic LC system combined with MS/MS has been successfully employed for the quantitative analysis of pharmaceutical compounds in human plasma. The capillary ceramic microfluidic LC/MS/MS system showed an approximate 20-fold (range 11-38-fold) increase in sensitivity compared with a standard 2.1 mm scale UPLC/MS/MS system for a broad range of analytes.

Renewable sorbent material for solid phase extraction with direct coupling of sequential injection analysis-bead injection to liquid chromatography-electrospray ionization tandem mass spectrometry.

The use of small scale renewable sorbent material for automated solid phase extraction of multi-residue pharmaceuticals in environmental samples exploiting the sequential injection analysis-bead injection with direct coupling to liquid chromatography-electrospray ionization tandem mass spectrometry (SIA-BI-μSPE-LC-ESI-MS/MS) is presented to determine beta-blockers, namely atenolol, sotalol, pindolol, acebutolol, timolol, metoprolol, labetalol, carazolol, propranolol and betaxolol. These compounds yielded the same product ions, therefore were affected in terms of quantification when flow injection analysis-mass spectrometry (FIA-MS) was used. Thus, analytes and matrix present in the sample travel together into the ionization source which can seriously affect the ionization efficiency and analyte signals due to monitoring over a short time period.

Fabrication and evaluation of an organic monolithic column based upon the polymerisation of hexyl methacrylate with 1,6-hexanediol ethoxylate diacrylate for the separation of small molecules by capillary liquid chromatography.

This paper describes the fabrication of a new porous monolith, prepared in 100μm i.d. capillaries by the co-polymerisation of hexyl methacrylate with 1,6-hexanediol ethoxylate diacrylate, poly (HMA-co-1,6 HEDA), in the presence of azobisisobutyronitrile, 1, 4-butanediol and 1-propanol were used as porogens for the monoliths; the monoliths were then used as a stationary phase for capillary liquid chromatography.

Practical applications of integrated microfluidics for peptide quantification.

Background: Increased pressure to obtain more, higher sensitivity data from less sample is especially critical for large peptides, whose already optimized LC-MS methods are heavily challenged by traditional ligand-binding assays.

Results: Critical bioanalytical assays were adapted to integrated microscale LC to reduce sample volumes while increasing sensitivity. Assays for teriparatide, glucagon and human insulin and five analogs were transferred from 2.

Organic solvent and temperature-enhanced ion chromatography-high resolution mass spectrometry for the determination of low molecular weight organic and inorganic anions.

There has recently been increased interest in coupling ion chromatography (IC) to high resolution mass spectrometry (HRMS) to enable highly sensitive and selective analysis. Herein, the first comprehensive study focusing on the direct coupling of suppressed IC to HRMS without the need for post-suppressor organic solvent modification is presented. Chromatographic selectivity and added HRMS sensitivity offered by organic solvent-modified IC eluents on a modern hyper-crosslinked polymeric anion-exchange resin (IonPac AS18) are shown using isocratic eluents containing 5-50 mM hydroxide with 0-80% methanol or acetonitrile for a range of low molecular weight anions (<165 Da).

Fabrication of an on-line enzyme micro-reactor coupled to liquid chromatography-tandem mass spectrometry for the digestion of recombinant human erythropoietin.

Our aim was to develop a fast and efficient on-line method using micro-reactors for the digestion and deglycosylation of recombinant human erythropoietin extracted from equine plasma. The trypsin digestion micro reactors were fabricated using fused silica capillaries with either a dextran-modified coating or a porous monolith that was able to immobilise the enzyme. These were both found to be reasonably robust and durable, with the trypsin immobilised on dextran-modified fused silica capillaries offering better reproducibility than the micro-reactor based upon covalent attachment of this enzyme to the polymer.

Investigating sub-2 μm particle stationary phase supercritical fluid chromatography coupled to mass spectrometry for chemical profiling of chamomile extracts.

Roman and German chamomile are widely used throughout the world. Chamomiles contain a wide variety of active constituents including sesquiterpene lactones. Various extraction techniques were performed on these two types of chamomile.

Ultra high resolution SFC-MS as a high throughput platform for metabolic phenotyping: application to metabolic profiling of rat and dog bile.

Ultra high resolution SFC-MS (on sub-2μm particles) coupled to mass spectrometry has been evaluated for the metabolic profiling of rat and dog bile. The selectivity of the SFC separation differed from that seen in previous reversed-phase UPLC-MS studies on bile, with the order of elution for analytes such as e.g.

Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity.

Inhaled nanomaterials present a challenge to traditional methods and understanding of respiratory toxicology. In this study, a non-targeted metabolomics approach was used to investigate relationships between nanoparticle hydrophobicity, inflammatory outcomes and the metabolic fingerprint in bronchoalveolar fluid. Measures of acute lung toxicity were assessed following single-dose intratracheal administration of nanoparticles with varying surface hydrophobicity (i.

Multidimensional LC-MS/MS enables simultaneous quantification of intact human insulin and five recombinant analogs in human plasma.

This work provides a multidimensional method for the simultaneous, direct quantification of intact human insulin and five insulin analogs in human plasma. This investigation solves both the selectivity and sensitivity problems encountered for accurate quantification of insulins in plasma since the former is not possible with conventional assays and the latter with conventional LC-MS/MS. The method uses a mixed-mode SPE and a multidimensional LC method including a solid-core particle column containing an anion exchange stationary phase.

High sensitivity LC-MS/MS method for direct quantification of human parathyroid 1-34 (teriparatide) in human plasma.

Teriparatide, the 1-34 fragment of human parathyroid hormone, is used to treat osteoporosis patients with a high risk of fracture by stimulating new bone formation. Routinely teriparatide is quantified using radioimmunoassay however the LC-MS/MS described here has the potential to achieve greater accuracy and precision, higher specificity, and is readily implemented in routine bioanalytical laboratories. Hence a complete method combining effective sample prep with appropriate LC separation and selected reaction monitoring (SRM) MS detection was developed to selectively separate teriparatide from closely related endogenous peptides and to reduce interferences.

Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease.

Abberant lipid metabolism is implicated in Alzheimer's disease (AD) pathophysiology, but the connections between AD and lipid metabolic pathways are not fully understood. To investigate plasma lipids in AD, a multiplatform screen (n = 35 by liquid chromatography-mass spectrometry and n = 35 by nuclear magnetic resonance) was developed, which enabled the comprehensive analysis of plasma from 3 groups (individuals with AD, individuals with mild cognitive impairment (MCI), and age-matched controls). This screen identified 3 phosphatidylcholine (PC) molecules that were significantly diminished in AD cases.

Detection of anionic energetic material residues in enhanced fingermarks on porous and non-porous surfaces using ion chromatography.

The ability to link criminal activity and identity using validated analytical approaches can be of great value to forensic scientists. Herein, the factors affecting the recovery and detection of inorganic and organic energetic material residues within chemically or physically enhanced fingermarks on paper and glass substrates are presented using micro-bore anion exchange chromatography with suppressed conductivity detection. Fingermarks on both surfaces were enhanced using aluminium powder or ninhydrin after spiking with model test mixtures or through contact with black-powder substitutes.

A facile and efficient strategy to enhance hydrophilicity of zwitterionic sulfoalkylbetaine type monoliths.

In order to prepare zwitterionic HILIC monolithic columns with high polarity, the highly hydrophilic monomer N,N-dimethyl-N-acryloyloxyethyl-N-(3-sulfopropyl)ammonium betaine (SPDA) and crosslinker N,N'-methylenebisacrylamide (MBA) were employed for developing a novel sulfoalkylbetaine type stationary phase. The polymerization parameters were systematically optimized in order to obtain a satisfactory performance for column permeability, mechanical stability, hydrophilicity, efficiency and selectivity. Compared to the previously reported poly(N,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl)ammonium betaine-co-ethylene dimethacrylate) (poly(SPE-co-EDMA)) monolith and the poly(SPDA-co-EDMA) monolith that we developed, a significantly enhanced hydrophilicity was obtained on the poly(SPDA-co-MBA) monolithic column, illustrated by the lowered critical composition of the mobile phase corresponding to the transition from the HILIC to the RP mode.

Comparison of reversed-phase and hydrophilic interaction liquid chromatography for the quantification of ephedrines using medium-resolution accurate mass spectrometry.

The separation and quantification of hydrophilic basic compounds continues to challenge reversed-phase chromatography. Ephedrines are an example where the optimal separation of their isomers and related substances is complicated due to both their hydrophilicity and basic nature. Here we study two potential ultra-high pressure liquid chromatography (UHPLC) methods and present the merits and limitations of a high pH reversed-phase and a hydrophilic interaction liquid chromatography (HILIC) approach for the separation and quantification of ephedrines for doping control analysis.

Development of a fast method for direct analysis of intact synthetic insulins in human plasma: the large peptide challenge.

Background: Intact insulins are difficult to analyze by LC-MS/MS due to nonspecific binding and poor sensitivity, solubility and fragmentation. This work aims to provide a simpler, faster LC-MS method and focuses on solving the above issues.

Results: A novel charged-surface chromatographic column produced peak widths for insulin that were significantly narrower than traditional C18 columns when using formic acid as mobile phase.

Investigation of basic mobile phases with positive ESI LC-MS for metabonomics studies.

Background: Accurate mass based LC-MS combined with statistical analysis is established as a core analytical technology for metabonomic studies. This is primarily due to the specificity, sensitivity and structural elucidation capabilities of the technology. The vast majority of these studies are performed using acidic-based mobile phases in combination with positive ESI mode LC-MS.