排序方式: 共有67条查询结果,搜索用时 31 毫秒
11.
12.
13.
14.
Imatinib (Gleevec) is an anticancer drug that inhibits specific protein kinases involved in cell proliferation. Whereas this drug is considered to have opened a new era, various mechanisms of resistance have been associated with imatinib relapse. Drug disposition in cancer cells including influx, efflux and drug metabolism is one mechanism that remains to be more thoroughly investigated. Moreover, recent genomic studies have revealed that some isozymes of cytochrome P450 (CYP) are possibly associated with the treatment outcome. Therefore, this research paper investigates the role of the activity of CYP1A1, 1A2, 1B1, 3A4, 4F2 and 4F3A/B on the fate of imatinib. First, a study of imatinib fragmentation was effected using electrospray triple-quadrupole and linear ion trap tandem mass spectrometers (MSn). Accurate mass determinations were performed at enhanced mass resolution for the identification of some product ions that were not predicted by two fragmentation softwares. Whereas the quadrupole MS was not designed for accurate mass measurement, delta mass errors were below 20 ppm. Then, a biotransformation study was effected in vitro. Imatinib metabolites were produced in microsomal incubations containing CYP isozymes. Imatinib and metabolites were extracted from incubation mixtures by protein precipitation, and supernatants were injected into a liquid chromatography equipment coupled with MS(n). Hydrophobic interaction liquid chromatography resolved one demethylated-, two hydroxy- and three N-oxide metabolites. Various rates of metabolite formation were observed between CYP isozymes. Liquid chromatography with deuterium oxide-containing mobile phase (H/D exchange) or incorporation of (18)O from H(2) (18)O added in the incubations was performed to elucidate the metabolite structure. Various MS(n) product scans (n < or = 4) were acquired on the linear ion trap or on the triple-quadrupole MS. Postulated structures of new metabolites are addressed. 相似文献
15.
García Ruano JL Gamboa AE Gutiérrez LG Martín Castro AM Rodríguez Ramos JH Yuste F 《Organic letters》2000,2(6):733-736
A new kind of chiral dienophiles, cyclic vinyl-p-tolylsulfilimines (2a and 2b), were obtained from the corresponding (Z)-sulfinylacrylonitriles with HBF(4) and methanol. The asymmetric Diels-Alder reaction of optically pure 2a with cyclopentadiene under mild thermal or catalyzed conditions afforded only the endo-4a adduct with complete endo and pi-facial selectivities. The ability of the sulfilimine moiety to enhance the dienophilic reactivity of the double bond is similar to that of the sulfinyl group. 相似文献
16.
The zeros in the complex z plane of the Whittaker function Wc/z,µ(z),closely related to spherical waves in the quantum-mechanicalCoulomb problem, are investigated for varying real values ofthe parameters c and µ 相似文献
17.
The GC-SNIF technique was used to obtain the olfactograms of shrimps, and their impact odorants were identified by MS hyphenated to the GC/olfactometric system and by comprehensive two-dimensional GC hyphenated to a time-of-flight MS. Confirming these identifications by their linear retention indices required application of a new strategy to compare retention indices between both instruments and with the in-house database. The aldehydes were confirmed by using their pentafluorophenylhydrazone derivatives, and 2-ethyl-3,5-dimethyl pyrazine had to be resolved from co-eluting compounds and then identified by multidimensional GC hyphenated to an MS and a sniff port. In both shrimp products, the most important odorants were trimethylamine, 2-acetyl-1-pyrroline, and 2-ethyl-3,5-dimethyl pyrazine, together with common carbonyl compounds. 相似文献
18.
J.-P. Besson S. Schilt E. Rochat L. Thévenaz 《Applied physics. B, Lasers and optics》2006,85(2-3):323-328
A photoacoustic sensor using a laser diode emitting near 1532 nm in combination with an erbium-doped fibre amplifier has been developed for ammonia trace gas analysis at atmospheric pressure. NH3 concentration measurements down to 6 ppb and a noise-equivalent detection limit below 3 ppb in dry air are demonstrated. Two wavelength-modulation schemes with 1f and 2f detection using a lock-in amplifier were investigated and compared to maximise the signal-to-noise ratio. A quantitative analysis of CO2 and H2O interference with NH3 is presented. Typical concentrations present in ambient air of 400 ppm CO2 and 1.15% H2O (50% relative humidity at 20 °C) result in a NH3 equivalent concentration of 36 ppb and 100 ppb, respectively. PACS 42.62.Fi; 43.35.Ud; 42.55.Px 相似文献
19.
Rochat B Bolay S Pascual A Calandra T Marchetti O 《Journal of mass spectrometry : JMS》2007,42(4):440-449
Caspofungin [(CASPO) MK-0991] is the first broad-spectrum anti-fungal agent of the echinocandin class approved for clinical use. Measurement of CASPO levels in blood might help monitor therapy in patients who are critically ill, in particular, if high-dose regimens or combinations of CASPO with other anti-fungals are used. The objective of this study was to develop a fast method for the measurement of CASPO levels in clinical blood samples using liquid chromatography coupled to a triple-quadrupole mass spectrometer. Stock solutions were prepared in plasma to avoid CASPO adsorption to glass and plastic surfaces during processing. CASPO and the internal standard (IS) were extracted from 100 microl of plasma using acetonitrile protein precipitation. The supernatant was diluted and directly injected into an analytical column (C8; 2.1 x 30 mm). The total run time was 15 min. CASPO was ionized by electrospray in the positive mode. CASPO and IS [M + 2H]2+ parent ions (m/z 547.3 and 547.8, respectively) and specific product ions (m/z 137.1 and 62.2, respectively) were used for the ion transitions. No carry over or cross-talk was observed on the column. The mean method recovery was 90 +/- 3%. Neither blood from different individuals (n = 6) nor the presence of concomitant drugs (n = 33) in plasma samples interfered with CASPO quantification. Quantification over time of the CASPO levels in plasma and whole blood was investigated at different pre-analysis storage conditions. The calibration curve included the clinically relevant CASPO concentration range from 0.04 to 20 microg/ml. Mean intra- and inter-day accuracy was 96.1 +/- 2.2% and 102.5 +/- 2.4%, respectively. Mean intra- and inter-day precision was 7.9 +/- 3.2% and 6.3 +/- 1.8%, respectively. This simple and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method may easily be implemented for monitoring CASPO therapy. 相似文献
20.
Sobhi HR Vatansever B Wortmann A Grouzmann E Rochat B 《Journal of chromatography. A》2011,1218(47):8536-8543
A generic LC-MS approach for the absolute quantification of undigested peptides in plasma at mid-picomolar levels is described. Nine human peptides namely, brain natriuretic peptide (BNP), substance P (SubP), parathyroid hormone 1-34 (PTH), C-peptide, orexines A and B (Orex-A and -B), oxytocin (Oxy), gonadoliberin-1 (gonadothropin releasing-hormone or luteinizing hormone-releasing hormone, LHRH) and α-melanotropin (α-MSH) were targeted. Plasma samples were extracted via a 2-step procedure: protein precipitation using 1vol of acetonitrile followed by ultrafiltration of supernatants on membranes with a MW cut-off of 30 kDa. By applying a specific LC-MS setup, large volumes of filtrates (e.g., 2×750 μL) were injected and the peptides were trapped on a 1mm i.d.×10 mm length C8 column using a 10× on-line dilution. Then, the peptides were back-flushed and a second on-line dilution (2×) was applied during the transfer step. The refocalized peptides were resolved on a 0.3mm i.d. C18 analytical column. Extraction recovery, matrix effect and limits of detection were evaluated. Our comprehensive protocol demonstrates a simple and efficient sample preparation procedure followed by the analysis of peptides with limits of detection in the mid-picomolar range. This generic approach can be applied for the determination of most therapeutic peptides and possibly for endogenous peptides with latest state-of-the-art instruments. 相似文献