Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six extraction media (acetic acid, EDTA, tetrabutylammonium hydroxide, NaOH, MeOH/H2O, acetonitrile/H2O) were tested for their ability to extract antimony (Sb) and arsenic (As) from freeze-dried poplar leaves, pine shoots and spruce shoots, as well as from a peat matrix. Additionally, the extraction efficiency of Sb and As in fresh and freeze-dried elder leaves and poplar leaves was compared. Total concentrations of Sb and As of aliquots (approximately 220 mg) of the freeze-dried samples were analysed by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS) after open vessel digestion with adequate mixtures of nitric, sulfuric, hydrochloric, and perchloric acid. Three reference materials GBW 07602 Bush Branches and Leaves, GBW 07604 Poplar Leaves, and SRM 1575 Pine Needles were analysed with every batch of samples to ensure the accuracy and precision of the applied analytical procedures. The use of hydrofluoric acid in the digestion mixture leads to distinctly lower As values (down to 40%) than actual concentrations in the investigated plant materials. Extraction efficiencies were generally low and lower for Sb than for As. Solutions of 0.66 mol L(-1) NaOH liberated highest amounts of Sb with approximately 10% for poplar leaves, and approximately 19% each for pine shoots and spruce shoots. Distinctly higher concentrations of As in NaOH extracts of poplar leaves (22%), pine shoots (32%), and spruce shoots (36%) were quantified. Extraction experiments resulted in yields of 7-9% from fresh elder and poplar leaves, respectively, and 8-13% for freeze-dried samples for Sb. The corresponding values for As were 10-35% for the fresh material and 7-37% for the freeze-dried samples.
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PMID:Extraction of antimony and arsenic from fresh and freeze-dried plant samples as determined by HG-AAS. 1122 51

The effects of liquid chromatography mobile phase buffer contents on the ionization and fragmentation of drug molecules in liquid chromatographic/ionspray tandem mass spectrometric (LC/MS/MS) determination were evaluated for simvastatin (SV) and its hydroxy acid (SVA). The objective was to improve further the sensitivity for SV by overcoming the unfavorable condition caused by the formation of multiple major adduct ions and multiple major fragment ions when using ammonium as LC mobile phase buffer. Mobile phases (70:30 acetonitrile-buffer, 2 mM, pH 4.5) with buffers made from ammonium, hydrazine or alkyl (methyl, ethyl, dimethyl or trimethyl)-substituted ammonium acetate were evaluated. Q1 scan and product ion scan spectra were obtained for SV in each of the mobile phases under optimized conditions. The results showed that, with the alkylammonium buffers, the alkylammonium-adducted SV was observed as the only major molecular ion, while the formation of other adduct ions ([M + H](+), [M + Na](+) and [M + K](+)) was successfully suppressed. On the other hand, product ion spectra with a single major fragment ion were not observed for any of the alkylammonium-adducted SVs. The affinity of the alkylammoniums to SV and the basicity of the alkylamines are believed to be factors influencing the formation and abundance of molecular and fragment ions, respectively. Methylammonium acetate provided the most favorable condition among all the buffers evaluated and improved the sensitivity several-fold for SV in LC/MS/MS quantitation compared with that obtained using ammonium acetate buffer. Better precision for SV in both Q1 and SRM scans was observed when using methylammonium buffer compared with those using ammonium buffer. The mobile phase buffer contents did not seem to affect the ionization, fragmentation and chromatography of SVA. The results of this evaluation can be applied to similar situations with other organic molecules in ionspray LC/MS/MS determination.
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PMID:Effects of liquid chromatography mobile phase buffer contents on the ionization and fragmentation of analytes in liquid chromatographic/ionspray tandem mass spectrometric determination. 1194 49

Trends in chromatographic shape selectivity with mobile phases consisting of mixtures of carbon dioxide and acetonitrile are investigated. Selectivity is evaluated as a function of mobile phase composition, temperature, and column bonding chemistry. SRM (standard reference material) 869a is used as a probe of shape selectivity, while the selectivity between triphenylene and o-terphenyl is used to investigate planarity selectivity. Four molecular mass 228 polyaromatic hydrocarbon isomers are used to investigate shape selectivity based on differences in length-to-breadth ratio. Shape selectivity trends as a function of temperature and column type are found to be similar to what is seen in reversed-phase liquid chromatography, while the trend seen as the amount of acetonitrile in the mobile phase increases is found to be different than in reversed-phase liquid chromatography. In addition, the effect of mobile phase density, i.e., solvent strength, on shape selectivity is investigated by examining shape selectivity as a function of density with neat carbon dioxide as the mobile phase.
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PMID:Chromatographic shape selectivity with carbon dioxide-acetonitrile mobile phases. Effect of mobile phase composition and density. 1235 Jan 26

Eleven beta-lactam antibiotics were analyzed in fortified and incurred beef kidney tissue using high-performance liquid chromatography/electrospray ionization/selective reaction monitoring-ion trap tandem mass spectrometry (LC/ESI-SRM-MS(n)). The analytes included: deacetylcephapirin, amoxicillin, cephapirin, desfuroylceftiofur cysteine disulfide (DCCD, a biomarker of ceftiofur), ampicillin, cefazolin, Pen G, oxacillin, cloxacillin, naficillin and dicloxicillin. Analytes were extracted with acetonitrile and water. Clean-up was performed by solid-phase extraction. Limits of confirmation in fortified tissue are as follows (tolerances or target levels in parentheses): deacetylcephapirin: 10-50 ng/g (100 ng/g); amoxacillin: 50-100 ng/g (10 ng/g); cephapirin: 10 ng/g (100 ng/g); DCCD: 500 ng/g (8000 ng/g); ampicillin: 10 ng/g (10 ng/g); cefazolin: 10 ng/g (10-50 ng/g); Pen G: 10 ng/g (50 ng/g); oxacillin: 10 ng/g (10-50 ng/g); cloxacillin: 10 ng/g (10 ng/g); naficillin: 10 ng/g (10-50 ng/g); dicloxacillin: 100-500 ng/g (10-50 ng/g). The present method was also tested on incurred kidney tissue that had previously been analyzed using a microbial assay. Good correspondence was found between the results from this new method and the bioassay. However, the present method is much more specific and, in several cases, more sensitive than the bioassay. In addition, the time of analysis is significantly shorter than the bioassay. We also found that SRM MS(n) was superior in the analysis of unknown incurred tissue than full spectrum MS(n). We also obtained an MS/MS spectrum of DCCD that is significantly at variance with previously published fragmentation spectra.
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PMID:Confirmatory analysis of beta-lactam antibiotics in kidney tissue by liquid chromatography/electrospray ionization selective reaction monitoring ion trap tandem mass spectrometry. 1266 Oct 18

High-performance liquid chromatography with mass spectrometric detection was used for the structure elucidation of eighteen primary and secondary amines and ammonia derivatised with naphthylisothiocyanate (NIT). A fragmentation scheme was established using reference compounds and the scheme was applied to real air samples from a tyre repair shop and from the air above a bacterial culture. The sampling was performed using a solid sorbent, XAD-2, impregnated with NIT, and the derivatives were extracted with acetonitrile and analysed with LC-MS/MS. A three-step process was developed for screening and identifying of volatile amines. The first step, selected reaction monitoring; SRM was applied in order to screen the samples for NIT derivatives. In the second step, a precursor ion scan gave the [M+H](+) ion, and in the third step a product ion scan gave the fragments needed for identification. The detection limits varied between 0.12 and 0.25 ng microL(-1) when screening for unknown derivatised amines. It was possible to separate and identify all the amines with the structural information obtained and the method proved to be general, sensitive and well suited for sampling and analysis of complex environmental samples.
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PMID:Development of a LC-MS/MS method for the analysis of volatile primary and secondary amines as NIT (naphthylisothiocyanate) derivatives. 1368 56

Methods for Vitamin B5 determination in food products remain limited by their low sensitivity and poor selectivity. Here, we have developed a liquid chromatography-mass spectrometry (LC-MS) method for Vitamin B5 determination in wide range of fortified food products. Vitamin B5 was extracted from food samples by heat treatment and analysed by LC-MS in the positive mode using electrospray ionisation (ESI). Vitamin B5 was quantified using hopantenic acid (HOPA) as internal standard after their separation on a C18 narrow-bore column with a gradient of mobile phase made of water/acetonitrile and trifluoroacetic acid (TFA) 0.025%. MS with single ion monitoring mode at mass m/z 220 was used for Vitamin B5 quantification. Calibration curve between 0.5 and 10 microg/ml of Vitamin B5 was linear (r2=0.9993) and the detection limit was determined to be 800 pg. The overall quantitative efficiency of the method was evaluated using Nestle reference sample (infant formula). The intra-assay RSD was 4.8% (n=8), the inter-assay RSD 6.4% (n=4) and the recoveries of the spiked samples were above 95%. Application of the LC-MS method to Vitamin B5 determination in wide range of fortified food products including three US National Institute of Standards and Technology (NIST) reference samples (RM 8435, RM 8415 and SRM 1546) shows consistent results with those obtained by microbiology and recoveries of Vitamin B5 between 93 and 104% for the spiked samples.
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PMID:Determination of vitamin B5 in a range of fortified food products by reversed-phase liquid chromatography-mass spectrometry with electrospray ionisation. 1506 69

The performance of matrix solid-phase dispersion (MSPD) for the extraction of polycyclic aromatic hydrocarbons (PAHs) in fish tissue is described. The suitability of different solid supports was tested as well as the influence on the extraction efficiency of the natural fat content in samples. Under optimal conditions 0.6-0.8 g of tissue sample, are dispersed with 2 g of octadecylsiloxane (C18) and 0.5 g of anhydrous sodium sulphate and transferred to the top of a polyethylene solid-phase extraction cartridge which already contains 2 g of florisil and 1 g of C18. Cartridges were eluted with acetonitrile. The analysis of the extracts was carried out by high-performance liquid chromatography (HPLC) coupled with fluorescence detection. The proposed method provides detection limits between 0.04 and 0.32 ng/g for the different considered PAHs, below the maximum levels established by the some regulatory bodies for the six PAHs after recent oil spill episodes and European Union regulations. Recoveries over 80% were obtained for all compounds. Accuracy validation was carried out using the US National Institute of Standards and Technology (NIST) SRM 2977 reference material.
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PMID:Application of matrix solid-phase dispersion in the analysis of priority polycyclic aromatic hydrocarbons in fish samples. 1600 45

A fast and accurate method to quantify the new immunosuppressive JAK3 inhibitor CP-690,550 in whole blood using a dual-pump liquid chromatography-liquid chromatography-mass spectrometry (LC/LC-MS) system was developed and validated in nonhuman primate blood. Before injection, blood samples were prepared by precipitation with a reagent that included methanol and acetonitrile (30:70, vol/vol) along with the internal standard (CP-istd). Column-switching LC/LC-MS analysis used online extraction followed by separation on a C8 analytic column and MS detection of the [M + H] CP-690,550 (m/z = 313.1) and CP internal standard (m/z = 288.1). Linearity was always better than r = 0.99 (n = 7) for CP-690,550 (range 2.5-750 ng/mL), with a lower limit of quantification (LLOQ) of 2.5 ng/mL. The intrarun accuracy and precision ranged from 103.0% to 105.4% and 2.7% to 4.3%, respectively (n = 5), and the interday precision ranged from 8.7% to 11.1%, and the interday accuracy ranged from 98.1% to 103.8% of nominal values (n = 14). The injection repeatability for the method was 1.3% (n = 7). Except for the LLOQ, the intraday accuracy and precision in human blood were also within 15% (n = 5). The combination of simple sample preparation and short analytic run time of this sensitive procedure makes it effective for monitoring the concentration of CP-690,550 in whole blood in organ-transplant recipients.
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PMID:Quantitative analysis of the immunosuppressant CP-690,550 in whole blood by column-switching high-performance liquid chromatography and mass spectrometry detection. 1617 34

Aberrant DNA methylation patterns resulting in gene transcriptional repression are observed in numerous cancers. Decitabine, a DNA methyltransferase inhibitor, is being clinically evaluated in patients with hematologic malignancies and solid tumors. Decitabine is rather unstable and decomposes to 1-beta-D-2'-deoxyribofuranosyl-3-guanylurea under basic conditions and several additional unknown products under neutral conditions. This has greatly limited application of pharmacokinetic assays to clinical development of decitabine. In this paper, a high-performance liquid chromatography/ultraviolet multi-stage mass spectrometry (HPLC-UV-MSn) study of the decomposition of decitabine in water and human plasma revealed that these previously unknown products are isomers of the intermediates formyl-1-beta-D-2'-deoxyribofuranosyl-3-guanylurea and 1-beta-D-2'-deoxyribofuranosyl-3-guanylurea. A HPLC tandem mass spectrometry (MS/MS) method for the determination of decitabine concentrations in human and rat plasma has been developed. This method was based on a specific fragmentation pathway of the molecular ion of decitabine at m/z 229 to generate a unique fragment ion at m/z 113 under collision-induced dissociation. Separation of decitabine and the stable internal standard dihydro-5-aza-cytidine from the endogenous interfering substance in plasma extract was carried out on a C18 Aquasil column under an isocratic elution with a mobile phase consisting of 5% water/acetonitrile and 10 mM ammonium formate. The detection of decitabine was via selected reaction monitoring (SRM, 229 > 113), and its ionization was enhanced by post-column addition of acetonitrile. Effects of sample preparation and handling parameters on the stability of decitabine were also evaluated in human plasma at various temperatures. The accuracy and precision of this assay showed a coefficient of variation of <15% over the range of 0.5-25 ng for rat plasma and 0.1-25 ng for human plasma injected on-column. Pharmacokinetics of decitabine in rats following intravenous doses of 1.0 and 5.0 mg/kg were characterized. In the rat, plasma concentration-time profiles were found to follow a biexponential decline and the pharmacokinetics was dose-independent. Application of this decitabine pharmacokinetic assay to human studies is therefore justified and ongoing.
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PMID:Characterization of decomposition products and preclinical and low dose clinical pharmacokinetics of decitabine (5-aza-2'-deoxycytidine) by a new liquid chromatography/tandem mass spectrometry quantification method. 1652 29

16 alpha-[(18)F]fluoro-17beta-estradiol ([(18)F]FES) is a radiotracer for imaging estrogen receptors by positron emission tomography. We developed a clinically applicable automatic preparation system for [(18)F]FES by modifying a cassette-type [(18)F]fluorodeoxyglucose synthesizer. Two milligrams of 3-O-methoxymethyl-16,17-O-sulfuryl-16-epiestriol in acetonitrile was heated at 105 degrees C for 10 min with dried [(18)F]fluoride. The resultant solution was evaporated and hydrolyzed with 0.2 N HCl in 90% acetonitrile/water at 95 degrees C for 10 min under pressurized condition. The neutralization was carried out with 2.8% NaHCO(3), and then the high-performance liquid chromatography (HPLC) purification was performed. The desired radioactive fraction was collected and the solvent was replaced by 10 ml of saline, and then passed through a 0.22-microm filter into a pyrogen-free vial as the final product. The HPLC purification data demonstrated that [(18)F]FES was synthesized with a yield of 76.4+/-1.9% (n=5). The yield as the final product for clinical use was 42.4+/-3.2% (n=5, decay corrected). The total preparation time was 88.2+/-6.4 min, including the HPLC purification and the solvent replacement process. The radiochemical purity of the final product was >99%, and the specific activity was more than 111 GBq/micromol. The final product was stable for more than 6 h in saline containing sodium ascorbate. This new preparation system enables us to produce [(18)F]FES safe for clinical use with high and reproducible yield.
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PMID:Automatic synthesis of 16 alpha-[(18)F]fluoro-17beta-estradiol using a cassette-type [(18)F]fluorodeoxyglucose synthesizer. 1654 84


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