A matrix-centered view of mass spectrometry platform innovation for volatilome research.

Volatile organic compounds (VOCs) are carbon-containing molecules with high vapor pressure and low water solubility that are released from biotic and abiotic matrices. Because they are in the gaseous phase, these compounds tend to remain undetected when using conventional metabolomic profiling methods. Despite this omission, efforts to profile VOCs can provide useful information related to metabolic status and identify potential signaling pathways or toxicological impacts in natural or engineered environments.

Systemic study of solvent-assisted active loading of gambogic acid into liposomes and its formulation optimization for improved delivery.

The solvent-assisted active loading technology (SALT) was developed for encapsulating a water insoluble weak base into the liposomal core in the presence of 5% DMSO. In this study, we further examined the effect of various water miscible solvents in promoting active loading of other types of drugs into liposomes. To achieve complete drug loading, the amount of solvent required must result in complete drug solubilization and membrane permeability enhancement, but must be below the threshold that induces liposomal aggregation or causes bilayer disruption.

Analysis and measurement of serotonin.

Serotonin, also known as 5-hydroxytryptamine, is an important signaling molecule in the central and peripheral nervous systems of humans. Acting through several receptor types, it helps regulate the normal functioning of the gastrointestinal tract, cardiovascular system and brain. Serotonin signaling has also been implicated in the etiology of several diseases, including depression, anxiety disorders, hypertension and irritable bowel syndrome.

Corrigendum: Long-Term Enrichment of Stress-Tolerant Cellulolytic Soil Populations following Timber Harvesting Evidenced by Multi-Omic Stable Isotope Probing.

[This corrects the article on p. 537 in vol. 8, PMID: 28443069.

Selective targeting and therapy of metastatic and multidrug resistant tumors using a long circulating podophyllotoxin nanoparticle.

Treatment options for metastatic and multidrug resistant (MDR) tumors are limited, and most of the chemotherapeutic drugs exhibit low efficacy against MDR cancers. An anti-tubulin agent podophyllotoxin (PPT) displays high potency against MDR tumor cells. However, due to its poor solubility and non-specificity, PPT cannot be used systemically.

Hepatic microsomal metabolism of BDE-47 and BDE-99 by lesser snow geese and Japanese quail.

In the present study, we investigated the oxidative biotransformation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) by liver microsomes from wild lesser snow geese (Chen caerulescens caerulescens) and domesticated Japanese quail (Coturnix japonica). Formation of hydroxy-metabolites was analyzed using an ultra-high performance liquid chromatography-tandem mass spectrometry-based method. Incubation of BDE-47 with avian liver microsomes produced sixteen hydroxy-metabolites, eight of which were identified using authentic standards.

Long-Term Enrichment of Stress-Tolerant Cellulolytic Soil Populations following Timber Harvesting Evidenced by Multi-Omic Stable Isotope Probing.

Soil management is vital for maintaining the productivity of commercial forests, yet the long-term impact of timber harvesting on soil microbial communities remains largely a matter of conjecture. Decomposition of plant biomass, comprised mainly of lignocellulose, has a broad impact on nutrient cycling, microbial activity and physicochemical characteristics of soil. At "Long-term Soil Productivity Study" sites in California dominated by Ponderosa pine, we tested whether clear-cut timber harvesting, accompanied by varying degrees of organic matter (OM) removal, affected the activity and structure of the cellulose-degrading microbial populations 16 years after harvesting.

Evaluation of hepatic biotransformation of polybrominated diphenyl ethers in the polar bear (Ursus maritimus).

Polar bears are at the top of the Arctic marine food chain and are subject to exposure and bioaccumulation of environmental chemicals of concern such as polybrominated diphenyl ethers (PBDEs), which were widely used as flame retardants. The aim of the present study was to evaluate the in vitro oxidative metabolism of 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) and 2,2',4,4',5-pentabrominated diphenyl ether (BDE-99) by polar bear liver microsomes. The identification and quantification of the hydroxy-brominated diphenyl ethers formed were assessed using an ultra-high performance liquid chromatography-tandem mass spectrometry-based method.

Arginine methylation in yeast proteins during stationary-phase growth and heat shock.

Arginine methyltransferases (RMTs) catalyze the methylation of arginine residues on proteins. We examined the effects of log-phase growth, stationary-phase growth, and heat shock on the formation of methylarginines on yeast proteins to determine if the conditions favor a particular type of methylation. Utilizing linear ion trap mass spectrometry, we identify methylarginines in wild-type and RMT deletion yeast strains using secondary product ion scans (MS(3)), and quantify the methylarginines using multiple reaction monitoring (MRM).

Levels of PBDEs in plasma of juvenile starlings (Sturnus vulgaris) from British Columbia, Canada and assessment of PBDE metabolism by avian liver microsomes.

In this study, the levels of polybrominated diphenyl ethers (PBDEs), HO-PBDEs, and bromophenols were monitored in starling chick plasma samples collected in Delta (British Columbia, Canada) close to the Vancouver municipal landfill and in Glen Valley, a rural area in British Columbia. The in vitro formation of hydroxylated metabolites of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) was also investigated using starling chick liver microsomes. Total PBDE plasma levels were approximately 60 times higher in starling chicks from Delta than from Glen Valley, suggesting that the Delta site is a major source of PBDEs for the local population of starlings and that PBDEs previously measured in starling eggs are bioavailable to chicks.

Sensitive, Efficient Quantitation of 13C-Enriched Nucleic Acids via Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry for Applications in Stable Isotope Probing.

Stable isotope probing (SIP) of nucleic acids is a powerful tool for studying the functional traits of microbial populations within complex communities, but SIP involves a number of technical challenges. Many of the difficulties in DNA-SIP and RNA-SIP experiments can be effectively overcome with an efficient, sensitive method for quantitating the isotopic enrichment of nucleic acids. Here, we present a sensitive method for quantitating (13)C enrichment of nucleic acids, requiring a few nanograms of sample, and we demonstrate its utility in typical DNA-SIP and RNA-SIP experiments.

A putative corticosteroid hormone in Pacific lamprey, Entosphenus tridentatus.

Great efforts have been put forth to elucidate the mechanisms of the stress response in vertebrates and demonstrate the conserved response across different vertebrate groups, ranging from similarities in the activation of the hypothalamic-pituitary-adrenal axis to the release and role of corticosteroids. There is however, still very little known about stress physiology in the Pacific lamprey (Entosphenus tridentatus), descendants of the earliest vertebrate lineage, the agnathans. In this paper we demonstrate that 11-deoxycortisol, a steroid precursor to cortisol in the steroidogenic pathway, may be a functional corticosteroid in Pacific lamprey.

A validated assay to quantitate serotonin in lamb plasma using ultrahigh-performance liquid chromatography-tandem mass spectrometry: applications with LC/MS3.

An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) method was developed and validated for the quantification of serotonin (5-HT) in lamb plasma using [(2)d(4)]-serotonin ([(2)d(4)]-5-HT) as an internal standard. Charcoal-stripped human plasma was used as the blank matrix during validation, and 5-HT was quantitated using selected reaction monitoring. The UHPLC/MS/MS system consisted of an Agilent 1290 Infinity ultrahigh-performance liquid chromatograph coupled with an AB SCIEX QTRAP(®) 5500 hybrid linear ion trap triple quadrupole mass spectrometer.

The safety and efficacy of short-term budesonide delivered via mucosal atomization device for chronic rhinosinusitis without nasal polyposis.

Background: Budesonide is a potent corticosteroid commonly prescribed for management of inflammation in chronic rhinosinusitis (CRS). The standard for prescribing budesonide is via impregnated nasal saline irrigation (INSI), although recently the mucosal atomization device (MAD) has emerged as a theoretically superior method of distributing medication into the sinuses. The MAD atomizes medication into small droplets and this is thought to enhance absorption and improve bioavailability.

Validated assay for the simultaneous determination of cortisol and budesonide in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry.

An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) method was developed and validated for the quantification of cortisol and budesonide in human plasma. Charcoal stripped human plasma was used as the blank matrix during validation. Cortisol, budesonide, and dexamethasone (internal standard) were extracted from human plasma with methyl-tert-butyl ether, and the chromatographic separation of the peaks was achieved using a Waters Acquity UPLC BEH C18, 1.

A correlation between cytotoxicity and reductase-mediated metabolism in cell lines treated with doxorubicin and daunorubicin.

The role of metabolism in daunorubicin (DAUN)- and doxorubicin (DOX)-associated toxicity in cancer patients is dependent on whether the parent drugs or major metabolites, doxorubicinol (DOXol) and daunorubicinol (DAUNol), are the more toxic species. Therefore, we examined whether an association exists between cytotoxicity and the metabolism of these drugs in cell lines from nine different tissues. Cytotoxicity studies using MTT [3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide] cell viability assays revealed that four cell lines [HepG2 (liver), HCT-15 (colon), NCI-H460 (lung), and A-498 (kidney)] were more tolerant to DAUN and DOX than the five remaining cell lines [H9c2 (heart), PC-3 (prostate), OVCAR-4 (ovary), PANC-1 (pancreas), and MCF-7 (breast)], based on significantly higher LC50 values at incubation times of 6, 24, and 48 hours.

A rapid and sensitive assay to quantify valproyl 1-O-acyl glucuronide in supernatants of sandwich-cultured rat hepatocytes using ultra-high performance liquid chromatography-tandem mass spectrometry.

A rapid and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of valproyl-1-O-acyl glucuronide (VPA-G) levels in hepatocyte culture medium. Chromatographic separation was achieved using a Waters Acquity UPLC(®) BEH C18 column (1.7μm, 2.

Biotransformation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) by human liver microsomes: identification of cytochrome P450 2B6 as the major enzyme involved.

Polybrominated diphenyl ethers (PBDEs) were widely used flame retardants that have become persistent environmental pollutants. In the present study, we investigated the in vitro oxidative metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a major PBDE detected in human tissue and environmental samples. Biotransformation of BDE-47 by pooled and individual human liver microsomes and by human recombinant cytochrome P450 (P450) enzymes was assessed using a liquid chromatography/tandem mass spectrometry-based method.

MS³ fragmentation patterns of monomethylarginine species and the quantification of all methylarginine species in yeast using MRM³.

Protein arginine methylation is one of the epigenetic modifications to proteins that is studied in yeast and is known to be involved in a number of human diseases. All eukaryotes produce Nη-monomethylarginine (ηMMA), asymmetric Nη1, Nη1-dimethylarginine (aDMA), and most produce symmetric Nη1, Nη2-dimethylarginine (sDMA) on proteins, but only yeast produce Nδ-monomethylarginine (δMMA). It has proven difficult to differentiate among all of these methylarginines using mass spectrometry.

Oxidative metabolism of BDE-99 by human liver microsomes: predominant role of CYP2B6.

Hydroxylated polybrominated diphenyl ethers (PBDEs) have been found in human serum, suggesting that they are formed by in vivo oxidative metabolism of PBDEs. However, the biotransformation of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), a major PBDE detected in human tissue and environmental samples, is poorly understood. In the present study, the oxidative metabolism of BDE-99 was assessed using pooled and single-donor human liver microsomes, a panel of human recombinant cytochrome P450 (CYP) enzymes, and CYP-specific antibodies.

Variability of phenotype in two sisters with pyridoxine dependent epilepsy.

Background: Pyridoxine dependent epilepsy (PDE) is characterized by neonatal epileptic encepahalopathy responsive to pharmacological doses of vitamin B6. Recently an autosomal recessive deficiency in Antiquitin (ALDH7A1), a gene involved in the catabolism of lysine has been identified as the underlying cause.

Case Report: In 21 and 23 year-old sisters, who had presented with neonatal / early infantile onset seizures, PDE was confirmed by elevated urinary alpha aminoadipic- 6- semialdehyde (α-AASA) excretion and compound heterozygosity for two known ALDH7A1 missense mutations.

The effect of operational stressors on ibuprofen pharmacokinetics.

Purpose: To determine whether two of the major operational stressors associated with military missions in Afghanistan: dry heat and long durations of soldier patrol (SP), alter the pharmacokinetics of ibuprofen.

Methods: Thirteen healthy and physically fit participants (19-32 years) were randomized to a four-arm crossover study, as follows: Arm 4 consisted of a simulated 2.5 h SP on a treadmill set at 4.

A validated enantioselective assay for the simultaneous quantitation of (R)-, (S)-fluoxetine and (R)-, (S)-norfluoxetine in ovine plasma using liquid chromatography with tandem mass spectrometry (LC/MS/MS).

A liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed and validated for the quantitation of (R)-, (S)-fluoxetine, and (R)-, (S)-norfluoxetine in ovine plasma. The analytes were extracted from ovine plasma at a basic pH using a single-step liquid-liquid extraction with methyl-tert-butyl ether. Chromatographic separation of all enantiomers was achieved using an AGP-chiral column with a run time of 10 min.

Validation of a novel in vitro assay using ultra performance liquid chromatography-mass spectrometry (UPLC/MS) to detect and quantify hydroxylated metabolites of BDE-99 in rat liver microsomes.

The purpose of this study was to develop and validate an ultra performance liquid chromatography-mass spectrometry (UPLC/MS) method to investigate the hepatic oxidative metabolism of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), a widely used flame retardant and ubiquitous environmental contaminant. Hydroxylated metabolites were extracted using liquid-to-liquid extraction, resolved on a C18 column with gradient elution and detected by mass spectrometry in single ion recording mode using electrospray negative ionization. The assay was validated for linearity, accuracy, precision, limit of quantification, range and recovery.