Zeper Abliz

Chinese Academy of Medical Sciences, Peping, Beijing, China

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Publications (88)293.51 Total impact

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    ABSTRACT: Detection and identification of unknown or low-level drug-related metabolites in complex biological materials is an ongoing challenge. A highly selective and sensitive method could be a possible solution. Here, we proposed a targeted data-independent acquisition and mining (TDIAM) strategy for the rapid identification of trace drug metabolites using ultra high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). In this strategy, raw data is acquired by a novel tm-MS scan, which contains an interleaved full MS scan with a targeted mass range and product ion scan by selecting all ions in the targeted mass range as precursor ions. For efficient discovery of me-tabolites, raw data are analyzed by a new post-acquisition processing method, Molecule- and Fragmentation-driven Mass Defect Filters (MF-MDFs), which was developed based on the fragmentation of parent drug to pick out molecular ions and fragment ions of potential metabolites from the complex matrix. When applying the proposed strategy to paclitaxel metab-olism research, we successfully identified 10 metabolites, among which six were not previously reported. The results demon-strated that TDIAM greatly improved throughput, detective sensitivity and selectivity, and more importantly, yielded almost the same spectrum as traditional HRMS/MS. Therefore, TDIAM provides structure-enriched evidence to confirm the exist-ence and elucidate the structures of metabolites. This strategy is suitable for identification of metabolites present at low con-centrations in a complex matrix, and has the potential to provide an efficient, sensitive, and labor-saving solution for drug metabolite research.
    Analytical Chemistry 07/2015; DOI:10.1021/acs.analchem.5b01205 · 5.83 Impact Factor
  • Fei Tang · Ying Bi · Jiuming He · Tiegang Li · Zeper Abliz · Xiaohao Wang
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    ABSTRACT: RationaleMass Spectrometry Imaging (MSI) is useful for analyzing biological samples directly, as a spatially resolved, label-free technique. Here we present a method for super-resolution reconstruction of sparse representation to improve resolution of MSI data.Methods Air Flow-Assisted Ionization Mass Spectrometry Imaging (AFAI-MSI) was used to acquire MSI data from ink samples, thyroid tumour samples, rat renal biopsies, and rat brain biopsy samples. Super-resolution reconstruction of sparse representation was adopted for the collected MSI data.ResultsAfter comparison of the reconstructed high-resolution image and the original high-resolution image, it is found that super-resolution reconstruction image is closer to the original high-resolution image than the image obtained with the interpolation method, and the highest Peak Signal-to-Noise Ratio (PSNR) difference value is over 1.4dB. Therefore, the application of the super-resolution reconstruction technique, based on sparse representation MSI, is feasible and effective.Conclusions The method proposed here not only improves the resolution of MSI in post-data processing, but also acquires fewer sampling points at the same resolution, thereby greatly reducing the sampling time, with great application value for large-volume sample MSI, high-resolution MSI, etc. Copyright © 2015 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 06/2015; 29(12). DOI:10.1002/rcm.7205 · 2.64 Impact Factor
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    ABSTRACT: The toxicities of polycyclic aromatic hydrocarbons (PAHs) have been extensively explored due to their carcinogenic and mutagenic potency; however, little is known about the metabolic responses to chronic environmental PAH exposure among the general population. In the present study, 566 healthy volunteers were dichotomized into exposed and control groups to investigate PAH-induced perturbations in the metabolic profiles. Nine urine PAH metabolites were measured by a sensitive LC-MS/MS method to comprehensively evaluate the PAH exposure level of each individual, and the metabolic profiles were characterized via a LC-MS-based metabolomic approach. PAH exposure was correlated to its metabolic outcomes by linear and logistic regression analysis. Metabolites related to amino acid, purine, lipid, and glucuronic acid metabolism were significantly changed in the exposed group. 1-Hydroxyphenanthrene and dodecadienylcarnitine have potential as sensitive and reliable biomarkers for PAH exposure and its metabolic outcomes, respectively, in general population. These findings generally support the hypothesis that environmental PAH exposure causes oxidative stress related effects in humans. The current study provides new insight into the early molecular events induced by PAH exposure in the actual environment.
    Journal of Proteome Research 05/2015; 14(6). DOI:10.1021/acs.jproteome.5b00134 · 5.00 Impact Factor
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    ABSTRACT: Conjugation of a cholesterol moiety to active compounds for cancer treatment or diagnosis is an attractive approach for increasing lipophilicity and improving loading into lipid carriers. We developed a highly sensitive and specific liquid chromatography atmospheric-pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) analytical method to investigate the in vivo plasma and tumor distribution characteristic of a cholesterol-paclitaxel conjugate (CHO-PTX) in nude mice with MDA-MB-231 human breast cancer xenografts. The samples were analyzed in positive ion, multiple reaction monitoring mode. The plasma and tumor tissue samples were processed by liquid-liquid extraction with methyl tert-butyl ether (MTBE). Docetaxel was used as the internal standard (IS) for sample processing and analysis. MS/MS detection was carried out by monitoring the transitions of m/z 1266.7→369.4 and 330.3 for CHO-PTX, and m/z 808.7→226.4 and 509.1 for IS. The calibration curves were linear over 100-25,000 ng/mL in mouse plasma and tumor homogenate samples. The limit of quantitation of CHO-PTX was 100 ng/mL in both matrices. The intra-day and inter-day precisions were less than 15%, and the accuracy was between -8.0% and 8.6% for both matrices. The developed method was successfully applied to measure CHO-PTX levels in plasma and tumor tissues in nude mice. The mean tumor concentrations in mice tumor tissues after intravenous administration of CHO-PTX emulsion at a dose equivalent to 20 mg/kg paclitaxel were 2022 ± 630 ng/mL ng/mL, 2516 ± 982 ng/mL, 3056 ± 1438 ng/mL, and 2367 ± 1029 ng/mL at 0.25, 3, 24, and 120 h, respectively. The accumulation of CHO-PTX in the tumor suggests that cholesteryl drug conjugates are a promising approach for medical treatment of various human cancers.
    Journal of Pharmaceutical and Biomedical Analysis 05/2015; DOI:10.1016/j.jpba.2015.05.023 · 2.83 Impact Factor
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    ABSTRACT: Elucidation of mechanism of action for drug candidates is fundamental to drug development, and is strongly facilitated by metabolomics. Herein, we developed an imaging metabolomics method based on air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) under ambient condition. This method was sub-sequently applied to simultaneously profile a novel anti-insomnia drug candidate, N6-(4-hydroxybenzyl)-adenosine (NHBA), and various endogenous metabolites in rat whole-body tissue sections after administration of NHBA. The principle component analysis (PCA) represented by an intuitive color-coding scheme based on hyperspectral imaging revealed in situ molecular profiling alterations in response to stimulation of NHBA, which are in a very low intensity and hidden in massive interferential peaks. We found that the abundance of six endogenous metabolites changed after drug administration. The spatiotemporal distribution indicated that five altered molecules, including neurotransmitter gamma-aminobutyric acid, neurotransmitter precursors choline and glycerophosphocholine, energy metabolism-related molecules adenosine (an endogenous sleep factor) and creatine, are closely associated with insomnia or other neurological disorders. These findings not only provide insights into deeply understanding on the mechanism of action of NHBA, but also demonstrate that the AFADESI-MSI-based imaging metabolomics is a powerful technique to investigate the molecular mechanism of drug action, especially for drug candidates with multi-target or undefined target in the preclinical study stage.
    Analytical Chemistry 04/2015; 87(10). DOI:10.1021/acs.analchem.5b00680 · 5.83 Impact Factor
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    ABSTRACT: Usually, insufficient intratumoral concentration of therapeutic drugs is one of the reasons for tumor treatment failure. However, little is known about intratumoral distribution of bromocriptine in non-responding prolactinomas because of extremely low drug concentration and small prolactinoma tissue samples. In this study, a sensitive, rapid and high-throughput quantitative bioanalytical method has been established by using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination of bromocriptine at trace level in human prolactinoma tissue. As little as 20mg (wet weight) tissue sample was required and total analysis time was 6min in this method. The assay quantifies over a linear range of 50fg/mg to 5pg/mg, and has a 25fg/mg limit of detection at a signal/noise ratio of 3. This validated method was successfully used to quantitatively determine bromocriptine in clinical post-operative bromocriptine-sensitive and -resistant prolactinomas. The results revealed bromocriptine concentration in resistant prolactinomas (0.49-1.25pg/mg) was significantly higher than that in sensitive prolactinomas (0.057-0.47pg/mg). These results provided direct evidence to demonstrate the reseaon for failure of bromocriptine treatment in some patients with prolactinoma was "intrinsic" tumor (cell) resistence, rather than insufficient drug concentration in tumor tissue. Additionaly, this HPLC-MS/MS method has been shown to be suitable for bromocriptine analysis in small amount tissue sample and could be adapted for therapeutic drug monitoring of other clinical medicine. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 03/2015; 989. DOI:10.1016/j.jchromb.2015.03.004 · 2.69 Impact Factor
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    ABSTRACT: A new multivariate statistical strategy for analyzing large datasets that are produced by imaging mass spectrometry (IMS) techniques is reported. The strategy divides the whole datacube of the sample into several subsets and analyses them one by one to obtain the results. Instead of analyzing the whole datacube at one time, the strategy makes the analysis easier and decreases the computation time greatly. In this report, the IMS data are produced by the air flow-assisted ionization IMS (AFAI-IMS). The strategy can be used in combination with most multivariate statistical analysis methods. In this paper, the strategy was combined with the principal component analysis (PCA) and partial least square analysis (PLS). It was proven to be effective by analyzing the handwriting sample. By using the strategy, the m/z corresponding to the specific lipids in rat brain tissue were distinguished successfully. Moreover the analysis time grew linearly instead of exponentially as the size of sample increased. The strategy developed in this study has enormous potential for searching for the m/z of potential biomarkers quickly and effectively.
    Chinese Chemical Letters 10/2014; 25(10). DOI:10.1016/j.cclet.2014.04.028 · 1.18 Impact Factor
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    ABSTRACT: The factor analysis method was applied in analysis of IMS data on the basis of air flow-assisted ionization imaging mass spectrometry. In the experiment, the optical image of sample, IMS images of special m/z and score images of different factors were investigated for the factor analysis. Meanwhile, the ion intensity strengths of certain m/z was used as the color values for IMS images and the scores of certain factor were used as the color values to complete the score images of different factors on different sample points.
    Chinese Journal of Analytical Chemistry 08/2014; 42(8):1099–1103. DOI:10.1016/S1872-2040(14)60757-X · 0.79 Impact Factor
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    ABSTRACT: A water-soluble pillar[10]arene was prepared. Its pH-responsive host–guest complexation with paraquat and application in constructing a supra-amphiphile were investigated.
    07/2014; 1(6). DOI:10.1039/C4QO00086B
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    ABSTRACT: RATIONALEImpurity analysis plays an important role to guarantee the quality and safety of pharmaceuticals. However, identification of impurities remains challenging, especially for those unknown or at trace levels. We present an integrated approach to detect and characterize the trace impurities in drugs.METHODS Based on liquid chromatography–tandem mass spectrometry (LC–MS/MS), an approach integrating automatic impurity screening method using multiple mass defect filters (MMDFs) and background subtraction (BS) was developed. This approach was used to acquire the structural and semi-quantitative information in a single sample run, and even to discover the impurity signals submerged by background and drug ions. This approach was illustrated by the comprehensive impurity analysis of levofloxacin.RESULTSThis approach was sensitive to detect impurities at the level of 0.02% with respect to levofloxacin concentration. Nineteen impurities were detected, fourteen of which were structurally characterized and eight impurities were reported for the first time. Impurity profiles of levofloxacin drug substances and degradation samples were obtained reliably. A plausible degradation pathway of levofloxacin was proposed including descarboxyl reaction under acid, piperazinyl ring cleavage degradation under light, and N-oxidation under oxidative condition.CONCLUSIONS The generic approach integrating LC–MS/MS and an automatic impurity screening method was developed for the detection, characterization and monitoring of impurities, especially those unknown or at trace levels. This approach was demonstrated to be rapid, sensitive and automatic for impurity profiling of drugs. Copyright © 2014 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 05/2014; 28(10). DOI:10.1002/rcm.6886 · 2.64 Impact Factor
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    ABSTRACT: The imaging mass spectrometry (IMS) technology has experienced a rapid development in recent years. A new IMS technology which is based on air flow assisted ionization (AFAI) was reported. It allows for the convenient pretreatment of the samples and can image a large area of sample in a single measurement with high sensitivity. The AFAI in DESI mode was used as the ion source in this paper. The new IMS method is named AFADESI-IMS. The adoption of assisted air flow makes the sample pretreatment easy and convenient. An optimization of the distance between the ion transport tube and MS orifice increases the sensitivity of the system. For data processing, a program based on MATLAB with the function of numerical analysis was developed. A theoretical imaging resolution of a few hundred microns can be achieved. The composite AFAI-IMS images of different target analytes were imaged with high sensitivity. A typical AFAI-IMS image of the whole-body section of a rat was obtained in a single analytical measurement. The ability to image a large area for relavent samples in a single measurement with high sensitivity and repeatability is a significant advantage. The method has enormous potentials in the MS imaging of large and complicated samples.
    Chinese Chemical Letters 05/2014; 25(5). DOI:10.1016/j.cclet.2014.01.046 · 1.18 Impact Factor
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    ABSTRACT: In this article, we present the design and construction of a series of supramolecular poly(benzyl ether) metallodendrimers featuring a well-defined hexagonal metallacycle at their cores via coordination-driven self-assembly. It was found that the second generation metallodendrimer 3c was able to hierarchically self-assemble into the regular vesicle-like structures. These nano-scale vesicles were monodisperse in shape and relatively monodisperse in size as detected in SEM, TEM, AFM, and DLS experiments. Notably, this kind of hierarchically formed vesicle-like nano-structures adopted a discrete metallacycle as the main skeleton, which is obviously different from many previous reports of nano-scale spherical architectures. Moreover, such supramolecular vesicle-like structures could encapsulate some fluorescent molecules like BODIPY and SRB, etc. By taking advantage of the dynamic nature of metal-ligand bonds, the disassembly and reassembly of the hexagonal cavity core could be reversibly controlled by the addition and removal of bromide ions, resulting in the transition from the vesicles to micelles. Thus, the controlled release of fluorescence dye was successfully realized by the halide-induced vesicles-micelles transition. These findings not only enrich the library of supramolecular metallodenrimers but also provide a new avenue to the construction of novel "smart" nano-materials, which have potential application in functional molecules delivery and release.
    Journal of the American Chemical Society 03/2014; 136(16). DOI:10.1021/ja500152a · 11.44 Impact Factor
  • Zhengtao Li · Jie Yang · Guocan Yu · Jiuming He · Zeper Abliz · Feihe Huang
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    ABSTRACT: By the introduction of 14 anionic carboxylate groups at its two rims, a water-soluble pillar[7]arene (WP7) was synthesized. Its pH-controlled complexation with paraquat G1 in water was investigated. Host WP7 and guest G1 formed a 1:1 [2]pseudorotaxane with a high association constant of (2.96 ± 0.31) × 10(9) M(-1) in water. Furthermore, we took advantage of this novel molecular recognition motif to fabricate a supra-amphiphile based on WP7 and an amphiphilic paraquat derivative G2. The morphologies and sizes of self-assemblies of G2 and WP7⊃G2 were identified by transmission electron microscopy and dynamic light scattering.
    Organic Letters 03/2014; 16(7). DOI:10.1021/ol500686r · 6.32 Impact Factor
  • Zhengtao Li · Jie Yang · Guocan Yu · Jiuming He · Zeper Abliz · Feihe Huang
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    ABSTRACT: A water-soluble pillar[9]arene was synthesized. Its pH-responsive host-guest binding to paraquat in water was studied.
    Chemical Communications 02/2014; 50(22). DOI:10.1039/c3cc49535c · 6.83 Impact Factor
  • 01/2014; 44(5):795. DOI:10.1360/N032014-00036
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    Meng-Lan He · Shuai Wu · Jiuming He · Zeper Abliz · Lin Xu
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    ABSTRACT: Through coordination-driven self-assembly, a novel naphthalimide-containing hexagonal metallocycle with well-defined shape and size has been successfully constructed, which was found to maintain the good performance on fluorescence detection of protons.
    RSC Advances 01/2014; 4(6):2605. DOI:10.1039/c3ra46500d · 3.84 Impact Factor
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    ABSTRACT: To screen the harmful substance 5-hydroxymethyl furfural content in commercially available traditional Chinese medicine injection which are commonly used, and to preliminarily evaluate the quality of these injections, 5-hydroxymethyl furfural was taken as an index. The contents of 5-hydroxymethyl furfural in 56 samples which consist of 23 kinds of traditional Chinese medicine injections and glucose injection were determined using LC-MS/MS, and 5-hydroxymethyl furfural was detected in 52 of these samples. The minimal content was 0.0038 microg x L(-1) and the maximum content was 1420 microg x mL(-1). The contents of 5-hydroxymethyl furfural were significantly different in traditional Chinese medicine injection which came from different kinds, manufacturers or batches. The results showed the quality difference of commercially available traditional Chinese medicine injection is significant taking 5-hydroxymethyl furfural content as assessment index. More attention should be paid to the safety of 5-hydroxymethyl furfural in traditional Chinese medicine injection, and unified limitation standard should be set to improve medication safety of traditional Chinese medicine injection.
    Yao xue xue bao = Acta pharmaceutica Sinica 11/2013; 48(11):1705-9.
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    ABSTRACT: Acquiring global information on plasma-endogenous metabolites challenges metabolomics. This study has been designed to investigate the suitability of integrated ionization rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC/MS/MS) for different kinds of metabolites in complex plasma, and provides an approach for plasma metabolomics in acquiring more comprehensive data of metabolites. Integrated ionization of electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photoionization (APPI) combined with RRLC/MS/MS has been carried out to perform analysis on the global plasma metabolome of healthy volunteers. The contributions to the total numbers of ion features by RRLC/MS with ESI, APCI, and APPI in positive and negative ion modes were calculated. Representative unique and identical ions were identified. The intensities of identical ions were compared. Each of ESI, APCI, and APPI coupled with RRLC/MS has its own advantage over the other two techniques for certain types of metabolites in plasma. LC/ESI-MS is very sensitive for detecting glycerophosphocholines, glycerophosphoethanolamines, acyl carnitines, bile acids, sulfate, etc. LC/APCI-MS is suitable for analyzing cyclic alcohols, fatty acids, and linoleic acids. LC/APPI-MS proves to be appropriate in detecting steroids, sphingolipids, some amino acids, nucleosides, and purines in plasma. It is suggested that the integrated ionization LC/MS approach should be applied for global plasma metabolomics. Moreover, the results obtained demonstrate that it is preferable to choose certain techniques from LC/ESI-MS, LC/APCI-MS, and LC/APPI-MS for metabolite target analysis. Copyright © 2013 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 09/2013; 27(18):2071-80. DOI:10.1002/rcm.6666 · 2.64 Impact Factor
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    ABSTRACT: A new family of 120° polysulfurated dipyridine donors have been successfully designed and synthesized, from which a series of novel rhomboidal and hexagonal supramolecular polysulfurated metallodendrimers were prepared via coordination-driven self-assembly. The structures of the newly designed polysulfurated metallodendrimers were characterized by multinuclear NMR (1H and 31P), mass spectrometry (CSI-TOF-MS), and elemental analysis. Moreover, the shape and size of these novel metallodendrimers were investigated with PM6 semi-empirical molecular orbital methods.
    Tetrahedron 07/2013; 69(29):5981–5988. DOI:10.1016/j.tet.2013.04.058 · 2.82 Impact Factor
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    ABSTRACT: It is essential to choose one pre-processing method for liquid chromatographymass spectrometry (LC-MS)-based metabolomics studies of urine samples in order to overcome their variability. However, the commonly used normalization methods do not substantially reduce the high variabilities arising from differences in urine concentration, especially for signal saturation (abundant metabolites exceed the dynamic range of the instrumentation), or missing values. Herein, a simple pre-acquisition strategy based on differential injection volumes calibrated by creatinine (to reduce the concentration differences between the samples), combined with normalization to "total useful MS signals" or "all MS signals", is proposed to overcome urine variabilities. This strategy was first systematically compared with other popular normalization methods by application to serially diluted urine samples. Then the method has been verified using rat urine samples of pre- and post-inoculation of Walker 256 carcinoma cells. The results showed that the calibration of injection volumes based on creatinine values could effectively eliminate intra-group differences caused by variations in the concentrations of urinary metabolites, thus giving better parallelism and clustering effects. In addition, peak area normalization could further eliminate intra-class differences. Therefore, the strategy of combining peak area normalization with calibration of injection volumes of urine samples based on their creatinine values is effective for solving problems associated with urinary metabolomics.
    Analytical Chemistry 07/2013; 85(16). DOI:10.1021/ac401400b · 5.83 Impact Factor