In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX

In vivo lung perfusion(IVLP)is a novel isolated lung technique developed to enable the local,in situ administration of high-dose chemotherapy to treat metastatic lung cancer.Combination therapy using folinic acid(FOL),5-fluorouracil(F),and oxaliplatin(OX)(FOLFOX)is routinely employed to treat several types of solid tumours in various tissues.However,F is characterized by large interpatient variability with respect to plasma concentration,which necessitates close monitoring during treatments using of this compound.Since plasma drug concentrations often do not reflect tissue drug concentrations,it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs.In this work,in vivo solid-phase microextraction(in vivo SPME)is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous(IV)trials.The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry(LC-HRMS)enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration(IVLP vs.IV)and the therapy itself.This study also shows that the immediate instrumental analysis of metabolomic samples is ideal,as long-term storage at80℃ results in changes in the metabolite content in the sample extracts.

Solid-phase microextraction of endogenous metabolites from intact tissue validated using a Biocrates standard reference method kit

Improved analytical methods for the metabolomic profiling of tissue samples are constantly needed.Currently,conventional sample preparation methods often involve tissue biopsy and/or homogenization,which disrupts the endogenous metabolome.In this study,solid-phase microextraction(SPME)fibers were used to monitor changes in endogenous compounds in homogenized and intact ovine lung tissue.Following SPME,a Biocrates AbsoluteIDQ assay was applied to make a downstream targeted metabolomics analysis and confirm the advantages of in vivo SPME metabolomics.The AbsoluteIDQ kit enabled the targeted analysis of over 100 metabolites via solid-liquid extraction and SPME.Statistical analysis revealed significant differences between conventional liquid extractions from homogenized tissue and SPME results for both homogenized and intact tissue samples.In addition,principal component analysis revealed separated clustering among all the three sample groups,indicating changes in the metabolome due to tissue homogenization and the chosen sample preparation method.Furthermore,clear differences in free metabolites were observed when extractions were performed on the intact and homogenized tissue using identical SPME procedures.Specifically,a direct comparison showed that 47 statistically distinct metabolites were detected between the homogenized and intact lung tissue samples(P<0.05)using mixed-mode SPME fibers.These changes were probably due to the disruptive homogenization of the tissue.This study's findings highlight both the importance of sample preparation in tissue-based metabolomics studies and SPME's unique ability to perform minimally invasive extractions without tissue biopsy or homogenization while providing broad metabolite coverage.

Comparison of different approaches for direct coupling of solid-phase microextraction to mass spectrometry for drugs of abuse analysis in plasma

The direct coupling of solid-phase microextraction(SPME)to mass spectrometry(MS)(SPME-MS)has proven to be an effective method for the fast screening and quantitative analysis of compounds in complex matrices such as blood and plasma.In recent years,our lab has developed three novel SPME-MS techniques:SPME-microfluidic open interface-MS(SPME-MOI-MS),coated blade spray-MS(CBS-MS),and SPME-probe electrospray ionization-MS(SPME-PESI-MS).The fast and high-throughput nature of these SPME-MS technologies makes them attractive options for point-of-care analysis and anti-doping testing.However,all these three techniques utilize different SPME geometries and were tested with different MS instruments.Lack of comparative data makes it difficult to determine which of these methodologies is the best option for any given application.This work fills this gap by making a comprehensive comparison of these three technologies with different SPME devices including SPME fibers,CBS blades,and SPME-PESI probes and SPME-liquid chromatography-MS(SPME-LC-MS)for the analysis of drugs of abuse using the same MS instrument.Furthermore,for the first time,we developed different desorption chambers for MOI-MS for coupling with SPME fibers,CBS blades,and SPME-PESI probes,thus illustrating the universality of this approach.In total,eight analytical methods were developed,with the experimental data showing that all the SPME-based methods provided good analytical performance with R^(2)of linearities larger than 0.9925,accuracies between 81%and 118%,and good precision with an RSD%≤13%.

Degradation of ciprofloxacin hydrochloride in a multiphase mixed system by subaquatic gas-liquid discharge plasma

In recent years, antibiotic pollution has become a serious threat to human health. In this study, a gas-liquid discharge plasma is developed to degrade ciprofloxacin hydrochloride in a multiphase mixed system containing inorganic and organic impurities. The discharge characteristics are analyzed by diagnosing the applied voltage and discharge current waveforms, as well as the optical emission spectra. The work investigates how degradation efficiency is affected by applied voltage, gas flow rate, treatment time, initial concentration as well as the addition of γ-Al_(2)O_(3) pellets and peanut straw. After 70 min, the degradation efficiency of ciprofloxacin hydrochloride in the multiphase mixed system reached 99.6%. Its removal efficiency increases as the initial concentration decreases and the applied voltage increases. Besides, there is still a good degradation efficiency of ciprofloxacin hydrochloride with the addition of peanut straw.The degradation mechanism of ciprofloxacin hydrochloride is investigated through the analysis of degraded intermediates and reactive species.

A Novel Method for Determining the Void Fraction in Gas-Liquid Multi-Phase Systems Using a Dynamic Conductivity Probe

Conventional conductivity methods for measuring the void fraction in gas-liquid multiphase systems are typically affected by accuracy problems due to the presence of fluid flow and salinity.This study presents a novel approach for determining the void fraction based on a reciprocating dynamic conductivity probe used to measure the liquid film thickness under forced annular-flow conditions.The measurement system comprises a cyclone,a conductivity probe,a probe reciprocating device,and a data acquisition and processing system.This method ensures that the flow pattern is adjusted to a forced annular flow,thereby minimizing the influence of complex and variable gas-liquid flow patterns on the measurement results;Moreover,it determines the liquid film thickness solely according to circuit connectivity rather than specific conductivity values,thereby mitigating the impact of salinity.The reliability of the measurement system is demonstrated through laboratory experiments.The experimental results indicate that,in a range of gas phase superficial velocities 5–20 m/s and liquid phase superficial velocities 0.079–0.48 m/s,the maximum measurement deviation for the void fraction is 4.23%.

A New Device for Gas-Liquid Flow Measurements Relying on Forced Annular Flow

A new measurement device,consisting of swirling blades and capsule-shaped throttling elements,is proposed in this study to eliminate typical measurement errors caused by complex flow patterns in gas-liquid flow.The swirling blades are used to transform the complex flow pattern into a forced annular flow.Drawing on the research of existing blockage flow meters and also exploiting the single-phase flow measurement theory,a formula is introduced to measure the phase-separated flow of gas and liquid.The formula requires the pressure ratio,Lockhart-Martinelli number(L-M number),and the gas phase Froude number.The unknown parameters appearing in the formula are fitted through numerical simulation using computational fluid dynamics(CFD),which involves a comprehensive analysis of the flow field inside the device from multiple perspectives,and takes into account the influence of pressure fluctuations.Finally,the measurement model is validated through an experimental error analysis.The results demonstrate that the measurement error can be maintained within±8%for various flow patterns,including stratified flow,bubble flow,and wave flow.

Enhanced degradation of tetracycline by gas-liquid discharge plasma coupled with g-C_(3)N_(4)/TiO_(2)

Plasma-catalysis is considered as one of the most promising technologies for antibiotic degradation in water.In the plasma-catalytic system,one of the factors affecting the degradation effect is the performance of the photocatalyst,which is usually restricted by the rapid recombination of electrons and holes as well as narrow light absorption range.In this research,a photocatalyst g-C_(3)N_(4)/TiO_(2) was prepared and coupled with gas-liquid discharge(GLD)to degrade tetracycline(TC).The performance was examined,and the degradation pathways and mechanisms were studied.Results show that a 90%degradation rate is achieved in the GLD with g-C_(3)N_(4)/TiO_(2) over a 10 min treatment.Increasing the pulse voltage is conducive to increasing the degradation rate,whereas the addition of excessive g-C_(3)N_(4)/TiO_(2) tends to precipitate agglomerates,resulting in a poor degradation efficiency.The redox properties of the g-C_(3)N_(4)/TiO_(2) surface promote the generation of oxidizing active species(H2O2,O3)in solution.Radical quenching experiments showed that·OH,hole(h^(+)),play important roles in the TC degradation by the discharge with g-C_(3)N_(4)/TiO_(2).Two potential degradation pathways were proposed based on the intermediates.The toxicity of tetracycline was reduced by treatment in the system.Furthermore,the g-C_(3)N_(4)/TiO_(2) composites exhibited excellent recoverability and stability.

Comparison of Headspace Solid-Phase Microextraction with Simultaneous Steam Distillation Extraction for the Analysis of the Volatile Constituents in Chinese Apricot

Volatile constituents in fully mature fruits of apricot （Prunus armeniaca L.） cultivar Xinshiji were extracted using headspace solid-phase microextraction （HS-SPME） and simultaneous steam distillation extraction （SSDE） and then analyzed using capillary gas chromatography and gas chromatography-mass spectrometry. A total of 70 components were identified by HSSPME, including 20 esters, 19 hydrocarbons, 5 alcohols, 5 ketones, 4 acids, 4 lactones, 3 aldehydes, and 10 miscellaneous components, with the esters being the dominant constituent. On the basis of the odor unit values, it is believed that the following compounds probably contributed to the fresh apricot odor： hexyl acetate, β-ionone, butyl acetate, （E）-2-hexenal, linalool, limonene, γ-decalactone, and hexanal. A total of 49 components were also detected by SSDE, including 13 hydrocarbons, 9 alcohols, 7 aldehydes, 9 esters, 4 ketones, 4 lactones, 2 acids, and 1 miscellaneous component, of which the monoterpene alcohols were the dominant constituents. It could be judged from the odor unit values that the following compounds were the major contributors to boiled apricot aroma： β-ionone, linalool, hexyl acetate, γ-dodecalactone, γ- decalactone, （E）-2-hexenal, hexanal, γ-octalactone, phenylacetaldehyde, butyl acetate, limonene, α-terpineol, and δ-decalactone. The results show that HS-SPME is a simple, rapid, and solvent-free method, which is an alternative to the classical SSDE.

Novel method for the determination of five carbamate pesticides in water samples by dispersive liquid-liquid microextraction combined with high performance liquid chromatography

A novel method for the determination of five carbamate pesticides （metolcarb, carbofuran, carbaryl, isoprocard and diethofencard） in water samples was developed by dispersive liquid-liquid microextraction （DLLME） coupled with high performance liquid chromatography-diode array detector （HPLC-DAD）. Some experimental parameters that influence the extraction efficiency were studied and optimized to obtain the best extraction results. Under the optimum conditions for the method, the calibration curve was linear in the concentration range from 5 to 1000 ng mL^-1 for all the five carbamate pesticides, with the correlation coefficients （r^2） varying from 0.9984 to 0.9994. Good enrichment factors were achieved ranging from 80 to 177- fold, depending on the compound. The limits of detection （LODs） （S/N = 3） were ranged from 0.1 to 0.5 ng mL^-1. The method has been successfully applied to the analysis of the pesticide residues in environmental water samples.

Ionic liquid based dispersive liquid-liquid microextraction of aromatic amines in water samples

In this work, a new microextraction method termed ionic liquid based dispersive liquid-liquid microextraction （IL-DLLME） was demonstrated for the extraction of 2-methylaniline, 4-chloroaniline, 1-naphthylamine and 4-aminobiphenyl in aqueous matrices. After extraction the ionic liquid （IL） phase was injected directly into the high performance liquid chromatography （HPLC） system for determination. Some parameters that might affect the extraction efficiency were optimized. Under the optimum conditions, good linear relationship, sensitivity and reproducibility were obtained. The limits of detection （LOD, S/N = 3） for the four analytes were in the range of 0.45-2.6 μg L^-1. The relative standard deviations （R.S.D., n = 6） were in the range of 6.2-9.8%. This method was applied for the analysis of the real water samples. The recoveries ranged from 93.4 to 106.4%. The main advantages of the method are high speed, high recovery, good repeatability and volatile organic solvent-free.

Analysis of α, β, γ-hexachlorocyclohexanes in water by novel activated carbon fiber-solid phase microextraction coupled with gas chromatography—mass spectrometry

A fast and simple method for determination of α, β, γ-hexachlorocyclohexanes (HCHs) in water using activated carbon fiber-solid phase microextraction(ACF-SPME) were studied. Results showed the performance of adsorption and desorption of three HCHs on ACF were excellent. A wide linear range from 10 to 100 μg/L and detection limits of the ng/L level were obtained using ACF-SPME with GC-MS in selected ion monitoring(SIM) acquisition mode. The proposed method was also successfully applied for determination of three HCHs in tap water. Compared to commercial fibers, ACF showed some advantages such as better resistance to solvents, higher thermal stability, longer lifetime and lower cost. The data demonstrated that GC-MS with ACF-SPME is well suitable for the analysis of HCHs in water.

Determination of urinary 8-hydroxy-2′-deoxyguanosine by capillary electrophoresis with molecularly imprinted monolith in-tube solid phase microextraction

Urinary 8-hydroxy-2 -deoxyguanosine(8-OHdG) is an excellent marker of oxidative DNA damage.In this study,employing guanosine as dummy template a novel molecularly imprinted(MIP) monolithic capillary column had been synthesized,and that was used as medium of in-tube solid phase microextraction(SPME).Coupled with capillary electrophoresis-electrochemical detection(CE-ECD),the system of extraction and detection of 8-OHdG in urinary sample had been developed.Because of its greater phase ratio combined with conv...

Enhancement of Sensitivity for Determination of Phenols in Environmental Water Samples by Single-drop Liquid Phase Microextraction Using Ionic Liquid prior to HPLC

A single-drop liquid phase micro-extraction procedure using 1-butyl-3-methylimidazolium hexafluorophosphate （[C4MIM][PF6]） was demonstrated for the sensitive determination of four phenols in water samples. Under the optimized conditions, the linear range of proposed method was excellent in the range of 0.5-100 μg·L^-1, the reproducibility （RSD, n=6） were in the range 5.4%-8.9% and detection limits （S/N=3） were 0.3, 0.3, 0.5 and 0.5 μg·L^-1 for 2, 4-dichlorophenol, 2-naphthol, 2-nitrophenol and 4-chlorophenol, respectively. The experimental results indicated that the effect of complex matrices natural water samples could be resolved with addition of sodium ethylene diamine tetracetate （EDTA） into the samples. Excellent spiked recoveries were achieved for these four phenols ranged from 86.2%-114.9 %. All these facts demonstrated that the proposed method with merits of low cost, simplicity and easy operating would be a competitive alternative procedure for the determination of such compounds at trace level.

Preparation of polypyrrole/nanosilica composite for solid-phase microextraction of bisphenol and phthalates migrated from containers to eye drops and injection solutions

This paper describes the electrodeposition of polyphosphate-doped polypyrrole/nanosilica nano-composite coating on steel wire for direct solid-phase microextraction of bisphenol A and five phthalates. We optimized influencing parameters on the extraction efficiency and morphology of the nanocomposite such as deposition potential, concentration of pyrrole and polyphosphate, deposition time and the nanosilica amount. Under the optimized conditions, characterization of the nanocomposite was inves-tigated by scanning electron microscopy and Fourier transform infra-red spectroscopy. Also, the factors related to the solid-phase microextraction method including desorption temperature and time, extrac-tion temperature and time, ionic strength and pH were studied in detail. Subsequently, the proposed method was validated by gas chromatography-mass spectrometry by thermal desorption and acceptable figures of merit were obtained. The linearity of the calibration curves was between 0.01 and 50 ng/mL with acceptable correlation coefficients (0.9956-0.9987) and limits of detection were in the range 0.002-0.01 ng/mL. Relative standard deviations in terms of intra-day and inter-day by five replicate analyses from aqueous solutions containing 0.1 ng/mL of target analytes were in the range 3.3%-5.4% and 5%-7.1%, respectively. Fiber-to-fiber reproducibilities were measured for three different fibers prepared in the same conditions and the results were between 7.3% and 9.8%. Also, extraction recoveries at two different concentrations were ≥96%. Finally, the suitability of the proposed method was demonstrated through its application to the analysis of some eye drops and injection solutions.

Dispersive Liquid-liquid Microextraction Combined with High-performance Liquid Chromatography for the Determination of Clozapine and Chlorpromazine in Urine

A simple method has been proposed for the determination of clozapine （CLZ） and chlorpromazine （CPZ） in human urine by dispersive liquid-liquid microextraction （DLLME） in combination with high-performance liquid chromatography-ultraviolet detector （HPLC-UV）. All important variables influencing the extraction efficiency, such as pH, types of the extraction solvent and the disperser solvent and their volume, ionic strength and centrifugation time were investigated and optimized. Under the optimal conditions, the limit of detection （LODs） and quantification （LOQs） of the method were 13 and 39 ng/mL for CLZ, and 2 and 6 ng/mL for CPZ, respectively. The relative standard deviations （RSDs） of the targets were less than 5.1% （C=0.100 μg/mL, n=9）. Good linear behaviors over the tested concentration ranges were obtained with the values of R20.999 for the targets. The absolute extraction efficiencies of CLZ and CPZ from the spiked blank urine samples were 98.3% and 97.8%, respectively. The applicability of the technique was validated by analyzing urine samples and the mean recoveries for spiked urine samples ranged from 93.3% to 105.0%. The method was successfully applied for the determination of CLZ and CPZ in real human urine.

Dispersive liquid-liquid microextraction,an effective tool for the determination of synthetic cannabinoids in oral fluid by liquid chromatography-tandem mass spectrometry

In the present work,dispersive liquid-liquid microextraction(DLLME)was used to extract six synthetic cannabinoids(JWH-018,JWH-019,JWH-073,JWH-200,or WIN 55,225,JWH-250,and AM-694)from oral fluids.A rapid baseline separation of the analytes was achieved on a bidentate octadecyl silica hydride phase(Cogent Bidentate C18;4.6 mm×250 mm,4μm)maintained at 37℃,by eluting in isocratic conditions(water:acetonitrile(25:75,V/V)).Detection was performed using positive electrospray ionization-tandem mass spectrometry.The parameters affecting DLLME(pH and ionic strength of the aqueous phase,type and volume of the extractant and dispersive solvent,vortex and centrifugation time)were optimized for maximizing yields.In particular,using 0.5 mL of oral fluid,acetonitrile(1 mL),was identified as the best option,both as a solvent to precipitate proteins and as a dispersing solvent in the DLLME procedure.To select an extraction solvent,a low transition temperature mixture(LTTM;composed of sesamol and chlorine chloride with a molar ratio of 1:3)and dichloromethane were compared;the latter(100μL)was proved to be a better extractant,with recoveries ranging from 73%to 101%by vortexing for 2 min.The method was validated according to the guidelines of Food and Drug Administration bioanalytical methods:intra-day and inter-day precisions ranged between 4%and 18%depending on the spike level and analyte;limits of detection spanned from 2 to 18 ng/mL;matrixmatched calibration curves were characterized by determination coefficients greater than 0.9914.Finally,the extraction procedure was compared with previous methods and with innovative techniques,presenting superior reliability,rapidity,simplicity,inexpensiveness,and efficiency.

Determination of Aromatic Components of Rosa davurica Pall. by Headspace Solid Phase Microextraction Combined with GC-MS

[Objectives] To determine the aromatic components of Rosa davurica Pall. [Methods] 42 kinds of aromatic components were identified from the flowers of R. davurica by headspace solid phase microextraction( HS-SPME) combined with gas chromatography-mass spectrometry( GC-MS). The main compounds were alcohols( 54. 88%) and aldehydes( 19. 55%). [Results] The top five components with the highest relative content were phenylethyl alcohol( 12. 69%),geraniol( 9. 85%),citronellol( 8. 80%),nerol( 7. 84%) and 2-n-pentylfuran( 7. 45%). [Conclusions] Headspace solid phase microextraction( HS-SPME) combined with gas chromatography-mass spectrometry( GC-MS) can provide basis for further development and utilization of R. davurica.

Determination of Amitraz in the Honey Samples by Dispersive Liquid-Liquid Microextraction Followed by Gas Chromatography—Flame Ionization Detection

Dispersive liquid-liquid microextraction (DLLME) followed by gas chromatography–flame ionization detection (GC-FID), as a simple, rapid and efficient method, was developed for the determination of amitraz in honey samples. This method involves the use of an appropriate mixture of the extraction and disperser solvents for the formation of a cloudy solution in 5.0 mL aqueous sample containing amitraz. After extraction, phase separation was performed by centrifugation and the concentrated amitraz in the sedimented phase was determined by gas chromatography—flame ionization detection (GC-FID). Some important parameters such as the type and volume of extraction and disperser solvents, and the effect of pH and salt on the extraction recovery of amitraz were investigated. Under the optimum conditions (13 μL of carbon tetrachloride as an extraction solvent, 1 mL of acetonitrile as a disperser solvent, no salt addition and pH 6) preconcentration factor and the extraction recovery were 955 and 95.5%, respectively. The linear range was 0.01 - 1.0 mg?kg–1 and the limit of detection was 0.0015 mg?kg–1. The relative standard deviation (RSD, n = 4) for 0.1 mg?kg–1 of amitraz was 3.2%. The recoveries of amitraz from honey samples at the spiking levels of 0.1 mg?kg-1 were 78.8 and 98.2%. The results indicated that DLLME is an efficient technique for the extraction of amitraz in honey samples.

Integration of GC-MS Based Non-Targeted Metabolic Profiling with Headspace Solid Phase Microextraction Enhances the Understanding of Volatile Differentiation in Tobacco Leaves from North Carolina, India and Brazil

In this report, gas chromatography-mass spectrometry (GC-MS) based non-targeted metabolomics is used to develop appropriate headspace solid phase microextractions (HS-SPME) to enhance the understanding of volatile complexity of flue-cured tobacco leaves. Non-targeted metabolic profiling of GC-MS shows that the extraction condition of HS-SPME at 100?C for 30 min provides a better metabolite profile than other extraction conditions tested. GC-MS and principal component analyses (PCA) show that among five types of fibers tested, 100 μm polydimethylsiloxane (PMDS), 65 μm polydimethylsiloxane/divinylbenzene (PMDS/DVB) and 75 μm carboxen/polydimethylsiloxane (CAR/ PMS) provide a better reproducible metabolite profile. Based on an appropriate PDMS extraction condition optimized, we use GC-MS analysis and PCA to compare metabolite profiles in flue-cured leaves of tobacco plants grown in North Carolina, India and Brazil, respectively. The resulting data of PCA show that the global metabolic profiles in North Carolina samples are separated from those in Brazil and India samples, two groups of which are characterized by a partially overlapped pattern. Several peaks that were differentially accumulated in samples were annotated to known metabolites by deconvolution analysis, such as norsolanadione, solavetivone and rishtin. Norsolanadione is detected only in Brazil samples. Solavetivone is detected in samples of India and Brazil but not in those of North Carolina. Rishtin is detected in samples of North Carolina and India but not in Brazil samples. These data indicate that not only can a non-targeted metabolic profiling approach enhance the understanding of volatile complexity, but also can identify marker volatile metabolites in tobacco leaves produced in different growth regions.

Flash Evaporation and Headspace Solid-phase Microextraction for the Analysis of the Essential Oils in Traditional Chinese Medicine,Houttuynia Cordata Thunb

We have investigated the use of flash evaporation, headspace solid-phase microextraction (HS-SPME) and steam distillation (SD) as sample concentration and preparation techniques for the analysis of volatile constituents present in Houttuynia cordata Thunb. The samples were analyzed by gas chromatography (GC) and identified by mass spectrometry (MS). Comparison studies were performed. It was found that the results obtained between Headspace solid-phase microextraction HS-SPME and SD techniques were in good agreement. Seventy-nine compounds in Houttuynia cordata Thunb were identified by MS. In flash evaporation, thirty-nine compounds were identified. Discrimination in the response for many constituents studied was not observed, which can be clearly observed in SD and HS-SPME techniques. As a conclusion, HS-SPME is a powerful tool for determining the volatile constitutes present in the Houttuynia cordata.