Liquid Chromatography Time-of-flight Mass Spectrometry Research Articles

Case Series of Novel Illicit Opioid-Related Deaths.

Novel illicit opioids, such as furanyl fentanyl and U-47700, are being encountered with increasing frequency in street heroin samples and have been confirmed in a series of overdose deaths in Tennessee. In this paper, we report the pathology and toxicology from 11 deaths involving furanyl fentanyl and U-47700. Routine toxicology was performed on postmortem femoral or antemortem hospital blood samples with targeted broad spectrum drug screening using liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS). Confirmation and quantitation of the opioid agonists U-47700 and furanyl fentanyl was performed by ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) using a novel method. Two cases were identified as containing U-47700 in whole blood (189 and 547 ng/mL), and nine cases contained furanyl fentanyl in whole blood, with concentrations ranging from 2.0 - 42.9 ng/mL. In all 11 cases, the manner of death was deemed accident, with drug intoxication being the primary cause of death; one case was complicated by smoke inhalation. All of the decedents were males ranging from 18-62 years, with the median age being 36 years old. The successful identification and confirmation of these novel illicit opioids in this case series relied on the comprehensive investigation and collaboration of scene investigation, forensic pathology, and forensic toxicology.

Metabolic engineering of Escherichia coli for the production of isoflavonoid-4'-O-methoxides and their biological activities.

Isoflavonoid representatives such as genistein and daidzein are highly potent anticancer, antibacterial, and antioxidant agents. It have been demonstrated that methylation of flavonoids enhanced the transporting ability, which lead to facilitated absorption and greatly increased bioavailability. In this paper, genetically engineered Escherichia coli was reconstructed by harboring E. coli K12-derived metK encoding S-adenosine-l-methionine (SAM) synthase (accession number: K02129) for enhancement of SAM as a precursor and Streptomyces avermitilis originated SaOMT2 (O-methyltransferase, accession number: NP_823558) for methylation of daidzein and genistein as preferred substrates. The formation of desired products via biotransformation including 4'-O-methyl-genistein and 4'-O-methyl-daidzein was confirmed individually by using chromatographical methods such as high-performance liquid chromatography, liquid chromatography/time-of-flight/mass spectrometry (LC-TOF-MS), and nuclear magnetic resonance (NMR), and NMR (1 H and 13 C). Furthermore, substrates concentration, incubation time, and media parameters were optimized using flask culture. Finally, the most fit conditions were applied for fed-batch fermentation with scale-up to 3L (working volume) to obtain the maximum yield of the products including 164.25µM (46.81mg/L) and 382.50µM (102.88mg/L) for 4'-O-methyl genistein and 4'-O-methyl daidzein, respectively. In particular, potent inhibitory activities of those isoflavonoid methoxides against the growth of cancer line (B16F10, AGS, and HepG2) and human umbilical vein endothelial cells were investigated and demonstrated. Taken together, this research work described the production of isoflavonoid-4'-O-methoxides by E.coli engineering, improvement of production, characterization of produced compounds, and preliminary invitro biological activities of the flavonoids being manufactured.

Germline BAP1 mutations induce a Warburg effect

Carriers of heterozygous germline BAP1 mutations (BAP1+/−) develop cancer. We studied plasma from 16 BAP1+/− individuals from 2 families carrying different germline BAP1 mutations and 30 BAP1 wild-type (BAP1WT) controls from these same families. Plasma samples were analyzed by liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS), ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-TQ-MS), and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found a clear separation in the metabolic profile between BAP1WT and BAP1+/− individuals. We confirmed the specificity of the data in vitro using 12 cell cultures of primary fibroblasts we derived from skin punch biopsies from 12/46 of these same individuals, 6 BAP1+/− carriers and 6 controls from both families. BAP1+/− fibroblasts displayed increased aerobic glycolysis and lactate secretion, and reduced mitochondrial respiration and ATP production compared with BAP1WT. siRNA-mediated downregulation of BAP1 in primary BAP1WT fibroblasts and in primary human mesothelial cells, led to the same reduced mitochondrial respiration and increased aerobic glycolysis as we detected in primary fibroblasts from carriers of BAP1+/− mutations. The plasma and cell culture results were highly reproducible and were specifically and only linked to BAP1 status and not to gender, age or family, or cell type, and required an intact BAP1 catalytic activity. Accordingly, we were able to build a metabolomic model capable of predicting BAP1 status with 100% accuracy using data from human plasma. Our data provide the first experimental evidence supporting the hypothesis that aerobic glycolysis, also known as the ‘Warburg effect’, does not necessarily occur as an adaptive process that is consequence of carcinogenesis, but rather that it may also predate malignancy by many years and facilitate carcinogenesis.

Urinary metabolomics reveals the therapeutic effect of HuangQi Injections in cisplatin-induced nephrotoxic rats

The side effects of cisplatin (CDDP), notably nephrotoxicity, greatly limited its use in clinical chemotherapy. HuangQi Injections (HI), a commonly used preparation of the well-known Chinese herbal medicine Astragali radix, appeared to be promising treatment for nephrotoxicity without compromising the anti-tumor activity of CDDP. In this study, the urinary metabolomics approach using liquid chromatography time of flight mass spectrometry (LC-TOF/MS) was developed to assess the toxicity-attenuation effects and corresponding mechanisms of HI on CDDP-exposed rats. As a result, successive administration of HI significantly recovered the decline of body weight and downregulated the abnormal increase of serum creatinine and urea. HI partly restored the CDDP-induced alteration of metabolic profiling back into normal condition. Totally 43 toxicity-attenuation potential biomarkers were screened and tentatively identified, which were involved in important metabolic pathways such as amino acid metabolism, TCA cycle, fatty acid metabolism, vitamin B6 metabolism and purine metabolism. The results clearly revealed that HI could alleviate CDDP-induced nephrotoxicity and improve the disturbed metabolic balance induced by repeated CDDP exposure. The present study provided reliable evidence for the protective effect of HI on CDDP-induced toxicity with the multi-target pharmacological characteristics.

Investigation of storage time-dependent alterations of enantioselective amino acid profiles in kimchi using liquid chromatography-time of flight mass spectrometry

Although naturally abundant amino acids are represented mainly by l-enantiomers, fermented foods are known to contain various d-amino acids. Enantiospecific profiles of food products can vary due to fermentation by bacteria, and such alterations may contribute to changes in food properties that would not be dependent exclusively on l-amino acids. Therefore, more attention should be paid to the study of temporal alterations of d-amino acid profiles during fermentation process. However, there have been very few studies reporting time-dependent profiling of d-amino acids because enantioseparation of widely targeted d-amino acids is technically difficult. This study aimed to achieve high throughput profiling of amino acids enantiomers. Enantioselective profiling of amino acids using CROWNPAK CR-I(+) column, liquid chromatography, time of flight mass spectrometry, and principle component analysis was performed to investigate time-dependent alterations in concentrations of free d- and l-amino acids in kimchi stored at 4°C or 25°C. We demonstrated significant changes in d- and l-amino acid profiles in kimchi stored at 25°C. In particular, concentrations of the amino acids d-Ala, d-Ser, d-allo-Ile, d-Leu, d-Asp, d-Glu, and d-Met became higher in kimchi with storage time. This is the first report of time-dependent alterations of d- and l-amino acid contents in kimchi. This study showed that our analytical method of enantioselective detection of amino acids using liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) with CROWNPAK CR-I(+) enables high throughput food screening and can be recommended for advanced studies of the relationship between d-amino acid content and food properties.

Synthesis of millimeter-scale sponge Fe/Cu bimetallic particles removing TBBPA and insights of degradation mechanism

Tetrabromobisphenol A (TBBPA) was a potential persistent organic pollutants. This study synthesized s-Fe/Cu bimetallic particles by decorated sponge iron (s-Fe) with Copper (Cu) to degrade TBBPA. S-Fe/Cu bimetallic particles was further characterized by XRD, XPS, SEM and EDS. The optimal TBBPA removal efficiency was 95.9%. Among the theoretical Cu mass loading increasing from 0wt% to 6wt%, 4wt% mass loading was the best; with TBBPA initial concentration increased from 5mg/L to 30mg/L, TBBPA removal efficiency decreased from 91.2% to 73.0%; also, when dosage increased from 10g/L to 30g/L, removal efficiency increased from 58.1% to 95.9%; pH 6.5 were beneficial to degrading TBBPA and the s-Fe/Cu bimetallic particles showed strong catalytic ability after 4 reuse cycle. Kinetic analysis showed that the degradation of TBBPA obeyed pseudo-first-order kinetics. In addition, Liquid Chromatography Time-of-Flight Mass Spectrometry (LC/TOF/MS) detected degradation products including debromination products, hydroxylation products, single aromatic ring products and O-methylating product, which demonstrated that the main degradation pathway were debromination, hydroxyl, β-scission and O-methylation reactions.

Construction of Three-Dimensional Hemin-Functionalized Graphene Hydrogel with High Mechanical Stability and Adsorption Capacity for Enhancing Photodegradation of Methylene Blue.

A three-dimensional hemin-functionalized graphene hydrogel (Hem/GH) was prepared by a facile self-assembly approach. The as-prepared Hem/GH showed good mechanical strength with a storage modulus of 609-642 kPa and a high adsorption capacity to organic dye contaminants (341 mg g-1 for rhodamine B). Moreover, Hem/GH could be used as a photosensitizer for the photocatalytic degradation of organic dyes and displayed superior photodegradation activity of methylene blue (MB). This result was better than that of counterparts such as graphene hydrogel (GH) and commercial catalyst P25. The excellent cycling performance of the Hem/GH was well maintained even after multiple cycles on adsorption process and photocatalytic reaction. Interestingly, after the photodegradation of MB, a light-induced pH change of the solution from alkaline pH 8.99 to acidic pH 3.82 was observed, and 10 wt % total organic carbon remained. The liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS) analysis confirmed the generation of acidic degradation products. The photocatalytic mechanism was further investigated by trapping experiments, which revealed that the MB degradation was driven mainly by the participation of O2•- radicals in the photocatalytic reaction. As an extended application, visually intuitive observation showed the as-prepared Hem/GH also had strong antibacterial properties. These results suggest that Hem/GH could be potentially used for practical application due to its high adsorption ability, excellent photocatalytic activity, and strong antibacterial properties.

Urine Comprehensive Drug Screen, Low Birth Weight and Withdrawal Symptoms in a Neonatal Unit: A Case Control Study.

Maternal drug abuse may influence neonatal outcomes. We compared neonatal outcomes of patients with urine screened positive for commonly abused drugs (CAD) versus those who were screened negative, and reviewed the pattern of drugs detected at a university teaching hospital. Urine samples collected from babies with suspected illicit drug exposure who were admitted to the neonatal unit were sent for comprehensive drug screen (CDS) performed by liquid chromatographytime- of-flight mass spectrometry (LC-TOF/MS). The screening library can detect more than 300 drugs and their metabolites. Fluorescence polarization immunoassay (FPIA) was also used to screen for cannabinoids which were not detected by the present LC-TOF/MS method. Symptoms suggestive of drug exposure and history of maternal substance misuse were recorded. Commonly abused drugs (CAD) including methadone, morphine, codeine, methamphetamine, ketamine, midazolam and heroin were present in the urine specimens of 46 (24.2%) of 190 neonates. Eighty-one (42.6%) urine samples screened positive for other drugs, which include antibiotics, lidocaine and pethidine administered during delivery. Drugs were undetectable in 33.2% samples. Urine positive for CAD was independently associated with maternal history of substance misuse (0.0001), birth-weight 2.5 kg (OR 2.9,0.01), neonatal withdrawal symptomatology (OR=8.89, 0.0001); but not with risk of preterm delivery. Logistic regression demonstrated that neonates with maternal history of substance misuse and CAD positivity were 5.99 (p=0.021) and 5.91 (0.0005) times more likely to have withdrawal symptoms. CADs are isolated in the CDS of nearly one-fourth of neonates. Neonates with maternal history of CAD exposure as evidenced by positive urine CDS are associated with low birth weight, and symptoms of drug withdrawal.

Photocatalytic degradation of bisphenol A over Rh/TiO2 suspensions in different water matrices

A series of noble metal-promoted Me/TiO2 (P25) photocatalysts (Me: Pt, Ru, Pd, Rh) of the same metal loading (0.5wt.%) were synthesized by the wet impregnation method and their photocatalytic activity was tested for the degradation of bisphenol A (BPA) under simulated solar irradiation. Results of H2 chemisorption, XRD, BET and UV–vis DRS experiments showed that dispersion of small metal crystallites on the TiO2 surface did not affect appreciably the phase composition (∼85% anatase), specific surface area (47–49m2/g) and optical band gap (3.2eV) of the semiconductor. Pt/TiO2 catalyst exhibited the higher efficiency under solar irradiation. In contrast to other Me/P25 catalysts investigated, the Rh/P25 catalyst exhibited increased activity for the title reaction in the presence of 20mg/L humic acid (HA), which was about 2.5 times higher than that obtained in ultrapure water (UPW). The apparent rate constant for the degradation of BPA in UPW+HA was found to increase proportionately with an increase of catalyst concentration in the range 50–400mg/L. The rate was not affected appreciably by the presence of inorganic ions contained in bottled water but decreased substantially in a secondary treated wastewater matrix. Results of liquid chromatography-time-of-flight-mass spectrometry (LC-TOF-MS) showed that degradation of BPA proceeds via two main pathways, which involve (i) hydroxylation, and (ii) cleavage of isopropylidene group with subsequent formation of para-substituted phenol derivatives.

Screening of lipophilic marine toxins in marine aquaculture environment using liquid chromatography–mass spectrometry

This study aimed to develop an exact mass suspect screening approach to perform finding of multiple lipophilic marine toxins (LMTs) in seawater, suspended particulate matter (SPM), and marine sediment from marine aquaculture area using liquid chromatography-time of flight mass spectrometry (LC-TOF/MS). The method was validated and proven to be reliable for the screening of various LMTs. Then, the method was applied to screen LMTs in marine environmental samples collected from mariculture area of Jiaozhou Bay, China. Okadaic acid (OA), pectenotoxin 2 (PTX2), etc were detected and tentatively identified. Positive detection results were confirmed by liquid chromatography-tandem mass spectrometry (LC–MS/MS), and contents of OA and PTX2 in seawater, SPM and marine sediment were also quantified. The mean concentration of OA ranged from 2.71 to 14.06 ng L−1 in seawater and from 0.78 to 3.34 ng g−1 dry weight in marine sediment. The mean concentration of PTX2 ranged from 0.86 to 7.90 ng L−1 in seawater, from 1.56 to 10.67 ng in SPM obtained from 1 L seawater sample and from 0.95 to 2.23 ng g−1 dry weight in marine sediment. The above results suggested that the proposed method was convenient and reliable for the screening of LMTs in different marine environmental samples. In addition, typical LMTs exist in different marine environmental media of the mariculture area of Jiaozhou Bay, China. Follow-up studies should focus on improving current understanding on the environmental behavior of these LMTs in the marine aquaculture environment.

The detection of endogenous 2’-deoxymugineic acid in olives (Olea europaea L.) indicates the biosynthesis of mugineic acid family phytosiderophores in non-graminaceous plants

ABSTRACTTo acquire iron (Fe), graminaceous plants secrete mugineic acid family phytosiderophores (MAs) from their roots into the rhizosphere. MAs are biosynthesized from methionine via nicotianamine (NA). It is thought that only graminaceous plants synthesize MAs, whereas non-graminaceous plants synthesize NA which is involved in translocation of Fe within plants. In this report, using liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS), we detected 2ʹ-deoxymugineic acid (DMA), and NA in xylem sap from olive (Olea europaea L.), which is a non-graminaceous dicot plant. High-performance liquid chromatography (HPLC) confirmed the presence of these compounds in olive leaves. A transcriptome analysis of young leaves revealed several contigs encoding the putative enzymes of NA synthase, NA aminotransferase and aldo-keto reductase, which are thought to catalyze the sequential synthesis of DMA from S-adenosyl methionine. Additionally, five contigs encoding YSL (yellow stripe 1 like) transporters were identified in olive leaves. Based on these results, we propose that both NA and DMA are synthesized in olive plants and contribute to maintaining Fe homeostasis in olive trees.

Solar light-induced degradation of ethyl paraben with CuOx/BiVO4: Statistical evaluation of operating factors and transformation by-products

In this work, the solar light-induced photocatalytic degradation of ethyl paraben (EP) was studied using CuOx/BiVO4 with 0.75wt.% copper loading, a relatively new photocatalyst that can exploit a large portion of the solar spectrum. The synthesized catalyst had a primary crystallite size of ca 37nm, a specific surface area of 1m2/g and a direct bandgap of 2.3eV. A factorial design methodology was implemented to evaluate the importance of EP concentration (500–1500μg/L), catalyst concentration (100–500mg/L), reaction time (10–60min), the presence of radical scavengers (pure water or 500mg/L bicarbonates) and initial solution pH (3–9) on EP removal. All individual effects were statistically significant and so was the second-order interaction of EP concentration with reaction time. Interestingly and differently from the majority of photocatalytic studies, the presence of bicarbonates promotes the photocatalytic degradation of ethyl paraben. The photocatalytic activity drops from 98% to 79% after five consecutive runs, possibly due to accumulation of oxidation by-products. Liquid chromatography-time of flight mass spectrometry (LC-TOF-MS) revealed that EP degradation occurs mainly via dealkylation followed by hydroxylation reactions and the formation of methyl paraben, 4-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 3,4-dihydroxybenzoic acid as primary transformation by-products.

Degradation of ethyl paraben by heat-activated persulfate oxidation: statistical evaluation of operating factors and transformation pathways.

A factorial design methodology was implemented to evaluate the importance of ethyl paraben (EP) concentration (500-1500μg/L), sodium persulfate concentration (400-500mg/L), temperature (40-60°C), reaction time (2-30min), water matrix (pure water or secondary treated wastewater), and initial solution pH (3-9) on EP removal by heat-activated persulfate oxidation. All individual effects, except the solution pH, were statistically significant and so were the second-order interactions of ethyl paraben concentration with temperature or the reaction time. The influence of the water matrix was crucial, and the efficiency of the process was lower in secondary treated wastewater due to the presence of natural organic matter and inorganic salts that compete with ethyl paraben for the reactive oxygen species. Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) was employed to identify major transformation by-products (TBPs); 13 compounds were detected as TBPs of EP. Degradation occurred through (i) hydroxylation, (ii) dealkylation, and (iii) oligomerization reactions leading to TBPs with ether and biphenyl structures. Oligomerization reactions were found to be the dominant pathway during the first steps of the reaction. The toxicity of 500μg/L EP in secondary treated wastewater was tested against marine bacteria Vibrio fischeri; toxicity increased during the first minutes due to the production of several TBPs, but it consistently decreased thereafter.

Oxidation of bisphenol A in water by heat-activated persulfate

The heat-activated persulfate oxidation of bisphenol A (BPA), a representative endocrine disrupting compound, was investigated with respect to the effect of several process variables on degradation rates. The activation temperature appears to be the single most important parameter, i.e. a temperature increase from 40 to 70 °C results in an 80-fold rate increase. Regarding initial BPA concentration, the reaction follows a pseudo-first order rate expression, where the kinetic constant decreases from 11.5 10−2 to 3.5 10−2 min−1 when BPA concentration increases from 110 to 440 μg/L. Reactions in actual water matrices, such as bottled water and secondary treated wastewater, are slower than in pure water since various organic/inorganic water constituents compete with BPA for being oxidized by the reactive oxidizing species; this was confirmed with experiments in pure water spiked with humic acid or bicarbonate. Interestingly though, the presence of chloride seems to promote BPA degradation. Furthermore, degradation is favored at near-neutral pH and increased sodium persulfate (SPS) concentrations.Experiments at an increased BPA concentration of 20 mg/L were performed to identify transformation by-products (TBPs), as well as assess the mineralization and toxicity of the treated samples. Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) revealed the formation of eleven TBPs of BPA and plausible pathways including hydroxylation, oxidation, cleavage and oligomerization reactions are proposed. Mineralization occurs slower than BPA degradation, while the toxicity to marine bacteria Vibrio fischeri increases during the early stages of the reaction but it progressively decreases thereafter.

Layer-by-layer functionalized porous Zinc sulfide nanospheres-based solid-phase extraction combined with liquid chromatography time-of-flight/mass and gas chromatography-mass spectrometry for the specific enrichment and identification of alkaloids from Crinum asiaticum var. sinicum

The current widely utilized polymer or C8, C18 end-capped material-based sorbents for solid-phase extraction could not capture alkaloids well only based on “like dissolves like” principle. In this paper, a layer-by-layer functionalized porous Zinc sulfide nanospheres-based solid-phase extraction (SPE) combined with liquid chromatography time-of-flight/mass spectrometry (LC-TOF/MS) and gas chromatography-mass spectrometry (GC-MS) was developed for the specific enrichment and identification of alkaloids from complex matrixes, Crinum asiaticum var. sinicum crude extracts. The functionalized porous Zinc sulfide nanospheres were prepared by the amidation reaction of poly-(acrylic acid) (PAA) homopolymer with amino groups onto the porous ZnS nanospheres. Tandem LC-TOF/MS spectrometry presented that the almost all of the twenty-three main peaks in elution fraction from the SPE could be inferred as alkaloids with ion of mass according to the nitrogen rule and hit formula with Peak View1.2@software from AB SCIEX, and seven alkaloids including two new found chemical entities were directly identified from their GC-MS spectra and retention indices. We believe that this SPE protocol can also be utilized in the future to selectively enrich alkaloids from extracts of other plant species.

Development of a liquid chromatography–tandem mass spectrometry method to address the increased utilization of umbilical cord in the assessment of in utero drug exposure

ObjectivesThe method described supports the detection of drugs and drug metabolites in the assessment of in utero drug exposure. The presented method employs liquid chromatography–tandem mass spectrometry (LC–MS/MS) as an alternative to a previously validated method using liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS). A reduction in required chromatographic time and consolidation from two injections to one injection per sample was desired to reduce turnaround time while maintaining the high specificity required. Design and methodsHomogenized and extracted umbilical cord samples were analyzed using LC-TOF/MS and LC–MS/MS. The LC–MS/MS chromatographic method used a 3.5min gradient with an injection-to-injection time of 5min. Dynamic multiple reaction monitoring was utilized. ResultsA 55% reduction in total analytical time was achieved by incorporating positive and negative mode acquisition in a single injection with the LC–MS/MS (5min cycle time) compared to the LC-TOF/MS method that required two total injections (one for positive mode, one for negative mode) and a combined ~11.5min cycle time. 514 patient samples were analyzed by both methods over 20 days. Of the 260 LC-TOF/MS negative samples, 259 were LC–MS/MS negative. Inter-assay imprecision conducted over 20days using the 50% and 150% QC samples yielded $_amp_$gt;97% qualitative acceptance and an average percent deviation from the target of 12% and 21%, respectively, using a single point calibration strategy. ConclusionsIn comparison to the existing LC-TOF/MS method, the LC–MS/MS method delivered the required specificity in a single injection with a 55% reduction in instrument time. Use of a single-point calibration standard and eight representative internal standards provided adequate accuracy for the quantitative assessment of quality control results with qualitative reporting of patient results.

Changes of the plasma metabolome of newly born piglets subjected to postnatal hypoxia and resuscitation with air

Perinatal hypoxic-ischemic brain damage is a major cause of mortality and morbidity in the neonatal period. Currently, limited ranges of biochemical tests assessing the intensity and duration of hypoxia are ready for clinical use. However, the need to initiate hypothermia therapy early after the clinical suspicion of hypoxic-ischemic encephalopathy requires the availability of early and reliable hypoxia markers. We have sought these biomarkers in an experimental model of hypoxia reoxygenation. Hypoxia and hypotension were induced in newborn piglets following a standardized model and reoxygenation was carried out using room air (RA). An untargeted liquid chromatography-time of flight mass spectrometry (LC-TOFMS) approach was used to assess changes in the metabolomic profile of plasma samples after intense hypoxia and upon reoxygenation. At the end of hypoxia, the plasma metabolome showed an increased plasma concentration of analytes reflecting a metabolic adaptation to prolonged anaerobiosis. However, after resuscitation, metabolite levels returned to the starting values. Severe hypoxia induces early, significant, and transient changes of specific metabolites in the plasma metabolome, which represent a snapshot of the biochemical adaptation of mammals to intense hypoxia. These metabolites could have applicability in predicting the severity of hypoxia in the clinical setting.

The characteristic of metabolics of female papillary thyroid carcinoma and its relationship with primary tumor size and cervical lymph node metastases

To analyze the metabolic profiles of the female papillary thyroid carcinoma (PTC) and the relationship between the metabolic profiles and primary tumor size and cervical lymph node metastasis using a metabolomics approach. Forty-three cases of female PTC were enrolled in this study. Gas chromatography-time-of-flight mass spectrometry and ultra performance liquid chromatography-time of flight-mass spectrometry were employed for analyzing metabolic profiles of tumor tissues and adjacent normal tissues in the female PTC. Cases were divided into Group T1 (tumor size≤2.0 cm) and Group T2 (tumor size>2.0 cm) according to the tumor size, and divided into Group N- (with negative cervical lymph node) and Group N+ (with positive cervical lymph node) according to the cervical lymph node conditions. We compared the metabolomic profiles between these groups. A panel of 46 differentially expressed metabolites was identified in the PTC specimens, compared with normal tissues. Increased metabolism of amino acid, purine and pyrimidine, tryptophan acid, one carbon, glycolysis, taurine and hypotaurine, and fatty acid were found in PTC tumors tissues. Amino acids, purine and pyridine, tryptophan, and carbon metabolism increased significantly in the tumor tissues of Group T2 compared with Group T1, while glycolysis, amino acid, purine and pyridine, tryptophan, and carbon metabolism increased significantly in the specimens of Group N+ . Distinct metabolic profiles were identified in the female PTC tissues, which were related to the primary tumor size and cervical lymph node metastases.

Simultaneous quantification of imatinib and CGP74588 in human plasma by liquid chromatography-time of flight mass spectrometry (LC-TOF-MS)

Imatinib mesylate is widely used for the treatment of different types of cancer, such as chronic myelogenous leukemia and gastrointestinal stromal tumors.

Extra-facile chiral separation of amino acid enantiomers by LC-TOFMS analysis

An extra-facile chiral liquid chromatography-time of flight mass spectrometry (LC-TOFMS) analytical method of amino acid enantiomers has been developed without a derivatization process. The enantioseparation of eighteen proteinogenic amino acids (except for proline) was simultaneously performed using a combination of a chiral column (CROWNPAK CR-I(+)) and a TOFMS within 15 min. An isocratic condition of a simple mobile phase comprising acetonitrile/water/trifluoroacetic acid (96/4/0.5) gave baseline separation of all underivatized amino acid enantiomers on the chiral column.