Radiosynthesis and evaluation of 188Re-c(RGDyK)-His as a novel radiotherapeutic agent for integrin αvβ3 targeting tumour

The successes of noninvasive methods to visualize and quantify integrin α_vβ₃ expression in vivo have paved the way for radiolabeling anti-integrin therapy in clinic. Arginine-glycine-aspartice (RGD) peptide and related derivatives labeled with radionuclides for radio-therapy, which specifically targeting integrin α_vβ₃-positive tumors, could be used to treat these tumors. We have labeled c(RGDyK)-His, a RGD derivative, with ¹⁸⁸Re and the radio-therapy efficiency has been evaluated in model nude mice. c(RGDyK)-His was labeled with ¹⁸⁸Re by chelating with [¹⁸⁸Re(CO)₃(H₂O)₃]⁺ under a slightly basic condition. The in vitro specific binding affinity to U87 MG cell lines and the biodistribution of ¹⁸⁸Re-c(RGDyK)-His in the animal tumor models was measured. The inhibitory effects of ¹⁸⁸Re-c(RGDyK)-His were observed more than 1 month, and evaluated by microPET/CT imaging with ¹⁸F-FDG. Results of in vivo, cell uptake demonstrated ¹⁸⁸Re-c(RGDyK)-His had a high specific binding affinity to receptor integrin α_vβ₃. In biodistribution experiment, ¹⁸⁸Re-c(RGDyK)-His was accumulated in the tumor and cleared fast from the normal tissues. In radiotherapy study, tumor growth inhibition was significantly higher in the treatment groups than in the control groups. These studies showed that ¹⁸⁸Re-c(RGDyK)-His could be effectively used for integrin α_vβ₃ targeting therapy. This may offer a potential therapeutic strategy for the treatment of integrin-positive tumors in clinic.     

Determination of four sulfonylurea herbicides in tea by matrix solid‐phase dispersion cleanup followed by dispersive liquid–liquid microextraction

Matrix solid‐phase dispersion combined with dispersive liquid–liquid microextraction has been developed as a new sample pretreatment method for the determination of four sulfonylurea herbicides (chlorsulfuron, bensulfuron‐methyl, chlorimuron‐ethyl, and pyrazosulfuron) in tea by high‐performance liquid chromatography with diode array detection. The extraction and cleanup by matrix solid‐phase dispersion was carried out by using CN‐silica as dispersant and carbon nanotubes as cleanup sorbent eluted with acidified dichloromethane. The eluent of matrix solid‐phase dispersion was evaporated and redissolved in 0.5 mL methanol, and used as the dispersive solvent of the following dispersive liquid–liquid microextraction procedure for further purification and enrichment of the target analytes before high‐performance liquid chromatography analysis. Under the optimum conditions, the method yielded a linear calibration curve in the concentration range from 5.0 to 10 000 ng/g for target analytes with a correlation coefficients (r²) ranging from 0.9959 to 0.9998. The limits of detection for the analytes were in the range of 1.31–2.81 ng/g. Recoveries of the four sulfonylurea herbicides at two fortification levels were between 72.8 and 110.6% with relative standard deviations lower than 6.95%. The method was successfully applied to the analysis of four sulfonylurea herbicides in several tea samples.     

Quantitative analysis and pharmacokinetics study of tigecycline in human serum using a validated sensitive liquid chromatography with tandem mass spectrometry method

Tigecycline, a novel intravenously administered glycylcycline antibiotic, currently plays a key role in the management of complicated multiorganism infections. However, current liquid chromatography with tandem mass spectrometry methods briefly describe parameters and the only reported internal standard was sometimes difficult to obtain. In our study, an updated liquid chromatography with tandem mass spectrometry method for the quantitative analysis of tigecycline in human serum was developed. Sample preparation involved precipitation with 20% trichloroacetic acid. Chromatographic separation of tigecycline and tetracycline (internal standard) was achieved on a Hypersil GOLD C₁₈ column using gradient elution. The selected reaction monitoring transitions were performed at m/z 586.1→513.2 for tigecycline and m/z 445.1→410.2 for tetracycline. The assay was linear over the concentration range of 5–2000 ng/mL. The intra‐ and interday precisions at three concentration levels (10, 100, and 1600 ng/mL) were <15% and their accuracies were within the range of 95.1–106.1%. The mean recovery ranged from 94.3 to 105.6% and the matrix effect from 92.1 to 97.6%. Tigecycline was stable under all tested conditions. This validated method was successfully applied to a pharmacokinetic study in critically ill patients. The data demonstrated that our method allows quantification of tigecycline in serum in a quick and reliable manner for widespread application.     

Novel chiral stationary phases based on peptoid combining a quinine/quinidine moiety through a C9‐position carbamate group

By connecting a quinine or quinidine moiety to the peptoid chain through the C9‐position carbamate group, we synthesized two new chiral selectors. After immobilizing them onto 3‐mercaptopropyl‐modified silica gel, two novel chiral stationary phases were prepared. With neutral, acid, and basic chiral compounds as analytes, we evaluated these two stationary phases and compared their chromatographic performance with chiral columns based on quinine tert‐butyl carbamate and the previous peptoid. From the resolution of neutral and basic analytes under normal‐phase mode, it was found that the new stationary phases exhibited much better enantioselectivity than the quinine tert‐butyl carbamate column; the peptoid moiety played an important role in enantiorecognition, which controlled the elution orders of enantiomers; the assisting role of the cinchona alkaloid moieties was observed in some separations. Under acid polar organic phase mode, it was proved that cinchona alkaloid moieties introduced excellent enantiorecognitions for chiral acid compounds; in some separations, the peptoid moiety affected enantioseparations as well. Overall, chiral moieties with specific enantioselectivity were demonstrated to improve the performance of peptoid chiral stationary phase efficiently.     

Rapid separation and characterization of diterpenoid alkaloids in processed roots of Aconitum carmichaeli using ultra high performance liquid chromatography coupled with hybrid linear ion trap‐Orbitrap tandem mass spectrometry

The lateral root of Aconitum carmichaeli, a popular traditional Chinese medicine, has been widely used to treat rheumatic diseases. For decades, diterpenoid alkaloids have dominated the phytochemical and biomedical research on this plant. In this study, a rapid and sensitive method based on ultra high performance liquid chromatography coupled with linear ion trap‐Orbitrap tandem mass spectrometry was developed to characterize the diterpenoid alkaloids in Aconitum carmichaeli. Based on an optimized chromatographic condition, more than 120 diterpenoid alkaloids were separated with good resolution. Using a systematic strategy that combines high resolution separation, highly accurate mass measurements and a good understanding of the diagnostic fragment‐based fragmentation patterns, these diterpenoid alkaloids were identified or tentatively identified. The identification of these chemicals provided essential data for further phytochemical studies and toxicity research of Aconitum carmichaeli. Moreover, the ultra high performance liquid chromatography with linear ion trap‐Orbitrap mass spectrometry platform was an effective and accurate tool for rapid qualitative analysis of secondary metabolite productions from natural resources.     

Graphene‐sensitized microporous membrane/solvent microextraction for the preconcentration of cinnamic acid derivatives in Rhizoma Typhonii

A novel graphene‐sensitized microporous membrane/solvent microextraction method named microporous membrane/graphene/solvent synergistic microextraction, coupled with high‐performance liquid chromatography and UV detection, was developed and introduced for the extraction and determination of three cinnamic acid derivatives in Rhizoma Typhonii. Several factors affecting performance were investigated and optimized, including the types of graphene and extraction solvent, concentration of graphene dispersed in octanol, sample phase pH, ionic strength, stirring rate, extraction time, extraction temperature, and sample volume. Under optimized conditions, the enrichment factors of cinnamic acid derivatives ranged from 75 to 269. Good linearities were obtained from 0.01 to 10 μg/mL for all analytes with regression coefficients between 0.9927 and 0.9994. The limits of quantification were <1 ng/mL, and satisfactory recoveries (99–104%) and precision (1.1–10.8%) were also achieved. The synergistic microextraction mechanism based on graphene sensitization was analyzed and described. The experimental results showed that the method was simple, sensitive, practical, and effective for the preconcentration and determination of cinnamic acid derivatives in Rhizoma Typhonii.     

Determination of the n‐octanol/water partition coefficients of weakly ionizable basic compounds by reversed‐phase high‐performance liquid chromatography with neutral model compounds

A strategy to utilize neutral model compounds for lipophilicity measurement of ionizable basic compounds by reversed‐phase high‐performance liquid chromatography is proposed in this paper. The applicability of the novel protocol was justified by theoretical derivation. Meanwhile, the linear relationships between logarithm of apparent n‐octanol/water partition coefficients (logK_ow′′) and logarithm of retention factors corresponding to the 100% aqueous fraction of mobile phase (logk_w) were established for a basic training set, a neutral training set and a mixed training set of these two. As proved in theory, the good linearity and external validation results indicated that the logK_ow′′–logk_w relationships obtained from a neutral model training set were always reliable regardless of mobile phase pH. Afterwards, the above relationships were adopted to determine the logK_ow of harmaline, a weakly dissociable alkaloid. As far as we know, this is the first report on experimental logK_ow data for harmaline (logK_ow = 2.28 ± 0.08). Introducing neutral compounds into a basic model training set or using neutral model compounds alone is recommended to measure the lipophilicity of weakly ionizable basic compounds especially those with high hydrophobicity for the advantages of more suitable model compound choices and convenient mobile phase pH control.     

Novel nanomaterials used for sample preparation for protein analysis

Sample preparation is of vital importance for proteomic analysis because of the high complexity of biological samples. The rapid development of novel nanomaterials with various compositions, morphologies, and proper surface modifications provides a category of powerful tools for the sample preparation for protein analysis. In this paper, we have summarized recent progresses for the applications of novel nanomaterials in sample preparation for the analysis of proteomes, especially for phosphoproteomes, glycoproteomes, and peptidoms. Several kinds of novel nanomaterials were also discussed for their use in other kinds of proteomics analysis.

Simultaneous determination of chlorpyrifos and 3,5,6-trichloro-2-pyridinol in duck muscle by modified QuEChERS coupled to gas chromatography tandem mass spectrometry (GC-MS/MS)

A rapid, specific, and sensitive method based on modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) coupled to gas chromatography tandem mass spectrometry (GC-MS/MS) was developed and validated for simultaneous determination of chlorpyrifos (CP) and its metabolite 3,5,6-trichloro-2-pyridinol (TCP) in duck muscle. The residues of CP and TCP were extracted by acidified acetonitrile. The fat layer of the extract was removed under ?20 °C, then the organic layer was evaporated. The analytes were derivatized by N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA) and cleaned up by a mixture of 150 mg MgSO₄, 25 mg graphitized carbon black (GCB), and 50 mg N-propylethylenediamine (PSA) to remove interference. The final extract was analyzed by GC-MS/MS. Recovery values at the spiking concentrations ranged from 86.2 to 92.3 % for CP and from 74.8 to 81.8 % for TCP, with relative standard deviations (RSDs) lower than 9.5 and 12.3, respectively. The correlation coefficients of CP (from 2 to 2,000 μg/kg) and TCP (from 1 to 1,000 μg/kg) were equal to or higher than 0.998. The limits of detection (LODs) were 0.3 and 0.15 μg/kg, and the limits of quantification (LOQs) were 1.0 and 0.5 μg/kg for CP and TCP in duck muscle, respectively. The average intra- and inter-day accuracy ranged from 84.6 to 91.2 % for CP and 75.6 to 82.3 % for TCP, and the intra- and inter-day precisions were from 5.8 to 8.2 % for CP and 6.5 to 11.9 % for TCP. Furthermore, the CP and TCP residues in duck muscle samples were detected for dietary risk assessment using the validated method.

Well‐Defined Flowerlike NdOCl Nanostructures: Nonaqueous Sol–Gel Synthesis,Nanoscale Characterization and Their Magnetic and Photoluminescence Properties

A facile nonaqueous solution route for the fabrication of NdOCl nanostructures based on a ligand‐exchange protocol and further thermal decomposition in organic medium, using only chloride salt as the neodymium source, is reported and the formation mechanism is proposed. The morphology, crystal structure, and chemical compositions of the sample were characterized at the nanoscale. XRD results and selected‐area electron diffraction patterns show that the sample is purely tetragonal NdOCl without any other impurity phases. TEM results show that the NdOCl nanostructures have a well‐defined flowerlike shape, which looks like a chrysanthemum just about to bloom. Magnetization measurements reveal that the NdOCl nanoflowers show room‐temperature ferromagnetism. The photoluminescence properties were also studied. These results are significant for fundamental research and promising applications of rare‐earth‐based nanostructures.