Highly sensitive fluorescence quantification of irinotecan in biological fluids with the aid of second-order advantage

A rapid,green and highly sensitive excitation-emission matrix（EEM） fluorescence method was proposed for analysis of irinotecan（CPT-11） in biological fluids including human plasma and urine samples of uncalibrated interferences with the aid of second-order advantage.Due to the serious spectral overlapping from biological matrices,the parallel factor analysis（PARAFAC） and the alternating normalization-weighted error（ANWE） have been recommended to perform directly calibration and overcome the problem which makes the traditional fluorospectrophotometer in trouble.Satisfactory results can be achieved.Furthermore, performance of the proposed method was evaluated based on figures of merit and some statistical parameters.The accuracy of both algorithms was validated by the elliptical joint confidence region（EJCR） test.The precision and repeatability were also investigated by the relative standard deviations（RSDs） of intra-day and inter-day.

Development of a novel stability indicating RP-HPLC method for quantification of Connexin43 mimetic peptide and determination of its degradation kinetics in biological fluids

Connexin43 mimetic peptide （Cx43MP） has been intensively investigated for its therapeutic effect in the management of inflammatory eye conditions, spinal cord injury, wound healing and iscbemia-induced brain damage. Here, we report on a validated stability-indicating reversed-phase high performance liquid chromatography （RP-HPLC） method for the quantification of Cx43MP under stress conditions. These included exposure to acid/base, light, oxidation and high temperature. In addition, the degradation kinetics of the peptide were evaluated in bovine vitreous and drug-free human plasma at 37℃. Detection of Cx43MP was carried out at 214 nm with a retention time of 7.5 min. The method showed excellent linearity over the concentration range of 0.9-250μg/mL （R2a0.998）, and the limits of detection （LOD） and quantification （LOQ） were found to be 0.90 and 2.98 μg/mL, respectively. The accuracy of the method determined by the mean percentage recovery at 7.8, 62.5 and 250μg/mL was 96.79%, 98.25% and 99.06% with a RSD of〈 2.2%. Accelerated stability studies revealed that Cx43MP was more sensitive to basic conditions and completely degraded within 24 h at 37℃（0% recovery） and within 12 h at 80℃ （0.34% recovery）. Cx43MP was found to be more stable in bovine vitreous （t1/2 slow= 171.8 min） compared to human plasma （t1/2slow = 39.3 min） at 37℃ according to the two phase degradation kinetic model. These findings are important for further pre-clinical development of Cx43MP.

Presence of hepcidin-25 in biological fluids: Bile,ascitic and pleural fluids

AIM: To examine body fluids such as ascitic fluid (AF),saliva,bile and pleural effusions for the presence of hepcidin using a novel radioimmunoassay (RIA).METHODS: Serum samples were collected from 25 healthy volunteers (mean age: 36 ± 11.9 years,11 males,14 females).In addition bile was obtained from 12 patients undergoing endoscopic retrograde cholangiopancreatography (mean age: 66.9 ± 16.7 years,M:F = 5:7).Saliva was collected from 17 healthy volunteers (mean age: 35 ± 9.9 years,M:F = 8:9).Pleural and AF were collected from 11 and 16 patients [(mean age: 72 ± 20.5 years,M:F = 7:4) and (mean age: 67.32 ± 15.2 years,M:F = 12:4)],respectively.All biological fluid samples (serum,exudative and transudative fluids) were tested for the presence of hepcidin-25 molecule using RIA.RESULTS: Hepcidin-25 was detected in all biological fluids tested.The mean ± SD hepcidin-25 in serum was 15.68 ± 15.7 ng/mL,bile 7.37 ± 7.4 ng/mL,saliva 3.4 ± 2.8 ng/mL,exudative fluid 65.64 ± 96.82 ng/mL and transudative fluid 14.1 ± 17.8 ng/mL.CONCLUSION: We provide clear evidence that hepcidin-25 is present in bile,saliva,pleural and ascitic fluids.Hepcidin is likely to play a role here in innate immunity.

HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC ANALYSIS OF KR-008 IN BIOLOGICAL FLUIDS

A high-performance liquid chromatographic method for the simultaneous determination of KR-008 and its metabolite in biological fluids was developed The samples were injected directly without further treatment,the compounds were separated and analysed on a reversed- phase column under isocratic conditions,including ion pairing.Concentrations in urine and bile were determined by an external standard method.The detection limit was 0.8μg/ml in urine.Preliminary data showed that,following i.p.administration(120mg/kg)of KR-008 to rats,approximately 2.8% of the dose was excreted in urine as unchanged compound and more than 8.9% was as a metabolite;in bile it was 0.73% excreted as unchanged form and above 0.29% as the metabolite.The peak biliary concentration of KR-008 was 0.39mg/ml at 20min after dosing.

Electrochemical Determination of Dapoxetine HCI in Biological Fluids Using Coated Wire Electrode

Coated wire sensor for potentiometric determination ofDAP （dapoxetine HCI） in pure form and in biological fluidsbased on DAP-TPB （dapoxetine-tetraphenyl borate） as the sensing element in the presence of DOP （dioctylphthalate） as the plasticizing solvent mediator was prepared. The best performance was obtained with a membrane composition of 10.0% （w/w） ion-pair, 45.0% DOP （w/w） and 45.0% PVC （w/w）. The electrode showed a Nemstian response （with a slope of 58.70 mV decade-1） for the concentration range of 4.2 × 10-5-1.0 ×10-2 mol/L. It illustrates a relatively fast response time in the whole concentration range （-15 s） in a pH range of 3.0-7.5. The selectivity coefficients were determined in relation to several inorganic and organic species. DAP is determined successfully in pure solutions and in biological fuids using the standard additions and petentiometric titrations methods.

Chemometrics-assisted excitation-emission fluorescence spectroscopy for simultaneous determination of ethoxyquin and tert-butylhydroquinone in biological fluid samples

A novel method applying simple, rapid, effective and inexpensive excitation-emission matrix （EEM） fluorescence spectroscopy coupled with second-order calibration method for simultaneous determination of ethoxyquin （EQ） and tert-butylhydroquinone （TBHQ） contents in biological fluid samples was developed. After a simple data preprocessing that was to insert zeros below the first-order Rayleigh scattering, the second-order calibration method based on the alternating normalization-weighed error （ANWE） algorithm was used to deal with EEM data. Via the introduced ＂second-order advantage＂, the individual con- centrations of the analytes of interest could be obtained even in the presence of uncalibrated interferences. The experimental concentration ranges for the analytes were as follows： EQ, from 4.58 to 20.6 p.g mL-1 in plasma and from 6.87 to 20.6 gg mL-1 in urine; TBHQ, from 4.49 to 20.2 ~tg mL-1 in plasma and from 6.73 to 22.4 I.tg mL-l in urine. The recoveries from spiked bi- ological fluid samples were in the ranges of 92.8%-106.2% for EQ and 94.6%-107.2% for TBHQ. These results demonstrate that the three-dimensional EEM fluorescence with second-order calibration method is a powerful tool for obtaining both EQ and TBHQ quantitative results in plasma and urine samples, and could be applied to more complex matrices.

Metabolomics profile in gastrointestinal cancers:Update and future perspectives

Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers;however,these tests are not useful as diagnostic screening since they have low specificity and low sensitivity.Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems,is now clear that this-omics could open a new way to study cancer.In the last years,nuclear magnetic resonance(NMR)metabolomics has demonstrated to be an optimal approach for diseases’diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers.For these reasons in this review,we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.

Using Gamma-Radiation for Drug Releasing from MWNT Vehicle

A drug delivery system via multi-walled carbon nanotube （MWNT） vehicle was synthesized in aqueous solution. MWNTs were first noncovalently functionalized with chitosan oligomers （CS） with a molecule weight of 4000-6000, making MWNTs water-soluble, and then a cancer ancillary drug tea polyphenols （TP） was conjugated mainly via the hydrogen bond between CS and TP molecules, making MWNTs efficient vehicle for drug delivering. The release of drug molecules can be realized by pH variation and γ-radiation, leading to new methods for controlling drug release from carbon nanotubes carrier. Due to the high penetrability of γ-rays, γ-radiation shows up new opportunities in controlled drug release, possibly facilitating the future cancer treatment in vivo.

A Novel Analytical Method of 1‑(3‑Trifluoromethylphenyl)piperazine and 1‑(3‑Chlorophenyl)piperazine in Fluids of Drug Addicts Using Liquid‑liquid Extraction–gas Chromatographic/Nitrogen–phosphorous Detection

In accordance with the research specifications and guidelines in China,we developed a novel experimental method to detect new piperazine‑type drugs,such as 1‑(3‑trifluoromethylphenyl)piperazine and 1‑(3‑chlorophenyl)piperazine.In this study,a new pretreatment method and gas chromatography(GC)/nitrogen–phosphorus detector detection technique were used to characterize these two kinds of drugs in urine and blood samples.For the purpose of isolation of these trace drugs from the samples,liquid‑liquid extraction/solid‑phase extraction was modified and validated for this specific study.The pretreatment method presented in this paper has many advantages,such as high recovery rate,high extraction efficiency,high detection sensitivity,low limit of detection,and simple operation.The GC/NPD instrument is popular in most laboratories because it can meet the routine requirements of forensic science.All these aspects make this combination of sample pretreatment and GC/NPD technique the most suitable choice for drug detection in biological samples.

Aerodynamic Performance of the Locust Wing in Gliding Mode at Low Reynolds Number

Gliding is an important flight mode for insects because it saves energy during long distance flight without wing flapping. In this study, we investigated the influence of locust wing corrugation on the aerodynamic performance in gliding mode at low Reynolds number. Numerical simulations using two-dimensional Navier-Stokes equations are applied to study the gliding flight, which reveals the interaction between forewing and hindwing. The lift of the corrugated airfoil in a locust wing decreases from the wing root to the tip. Simulation results show that the pressure drags on the forewing and hindwing increase with an increase in wing thickness; while the lift-drag ratio of the airfoil is marginally affected by the corrugation on the airfoil. Geometric parameters analysis of the locust wing is also carried out, which includes the corrugation height, the corrugation placement and the shapes of leading and trailing edges.

Numerical and experimental studies of hydrodynamics of flapping foils

The flapping foil based on bionics is a sort of simplified models which imitate the motion of wings or fins of fish or birds. In this paper, a universal kinematic model with three degrees of freedom is adopted and the motion parallel to the flow direction is considered. The force coefficients, the torque coefficient, and the flow field characteristics are extracted and analyzed. Then the propulsive efficiency is calculated. The influence of the motion parameters on the hydrodynamic performance of the bionic foil is studied. The results show that the motion parameters play important roles in the hydrodynamic performance of the flapping foil. To validate the reliability of the numerical method used in this paper, an experiment platform is designed and verification experiments are carried out. Through the comparison, it is found that the numerical results compare well with the experimental results, to show that the adopted numerical method is reliable. The results of this paper provide a theoretical reference for the design of underwater vehicles based on the flapping propulsion.

Determination of Ciprofloxacin in Human Plasma and Urine by Precolumn Derivatization High Performance Liquid Chromatography with Fluorescence Detection

A sensitive, simple and selective high-performance liquid chromatographic （HPLC） method was developed for the determination of ciprofloxacin in biological fluids. The method is based on the reaction between the drug and 4-chloro-7-nitrobenzofurazan （NBD-C1） in borate buffer of pH 9.0 to yield a highly fluorescent derivative that is measured at 535 nm after excitation at 464 nm. The calibration curves were linear over the concentration ranges of 25--3000 and 50--3000 ng·mL -1 for plasma and urine, respectively. The mean recovery of ciprofloxacin from plasma and urine was 98.37% and 98.40%, respectively. The method was found to be sensitive, precise, accurate, and reproducible. All of the validation parameters were within the acceptance range.

Dual-Emission Carbonized Polymer Dots Combined with Metal Ions as a Single-Component Fluorescence Sensor Array for Pattern Recognition of Glycosaminoglycans

Herein,a novel dual-emission fluorescence sensor array of carbonized polymer dots(CPDs)-Cu^(2+)has been proposed,in which CPDs were prepared by one-pot hydrothermal method and Cu^(2+)acting as a quencher was combined with CPDs by electrostatic interaction.Four negatively charged glycosaminoglycans(GAGs)bearing different hydrophilic groups showed variable binding affinities towards CPDs-Cu^(2+).Upon reacting with these GAGs,the different fluorescence response signals of CPDs-Cu^(2+)can be further differentiated by principal component analysis(PCA).The CPDs-Cu^(2+)sensor array,not only allows the identification of four similarly structured GAGs,but also realizes the discrimination of different concentrations of the same GAGs and their mixtures.Remarkably,the identification of GAGs in biological fluids can also be achieved using our proposed single-component sensor array,validating its application potential.This new strategy avoids multiple sensing probes,broadens the application of tongue-mimic sensor arrays and provides a viable idea for the development of single component sensing platforms.