Direct Liquid Extraction Research Articles

Microextraction-TQ-ICP-MS for the Direct Analysis of U and Pu from Cotton Swipes.

The microextraction sampling technique was integrated with triple quadrupole─inductively coupled plasma-mass spectrometry (TQ-ICP-MS) to directly sample and measure the isotopic compositions of uranium (U) and plutonium (Pu) from cotton swipes. Once extracted, the U/Pu were directed into the TQ-ICP-MS instrument for isotopic determination. Carbon dioxide (CO2) and helium (He) gases were delivered to a collision reaction cell within the ICP-MS system for ion separation. The CO2 reacts with the U+ forming UO+ which is ultimately separated from the Pu+ ions of interest in the third quadrupole. This study demonstrates direct liquid extraction of U/Pu from a solid surface and subsequent measurement by TQ-ICP-MS in <60 s. Flow rates were optimized (0.3 mL min-1 CO2 and 5 mL min-1 He) in the reaction cell of the ICP-MS system to maximize the Pu signal while minimizing U interferences (i.e., 238U+ tail and 238UH+) at m/z 239. Low levels of Pu (∼2 pg) were deposited on a cotton swipe along with U at concentrations ranging from 20 to 200 ng. The 240Pu/239Pu ratio was measured with <7% relative difference from the certified value at all U concentrations. Major and minor U isotope ratios were also measured with <4% relative difference. This highlights that the microextraction-TQ-ICP-MS method can extract a mixed U/Pu sample directly from a cotton swipe and measure both isotopic systems without chemical separation.

LMJSSP for analysis of prophylactic lubricants, spermicides and residues

DNA evidence in sexual assault cases have proven increasingly difficult to obtain and analyse due to increased condom use. With more interest in alternatives to DNA evidence, prophylactic lubricants, spermicides and residues may be interesting prospects. Current interest in the analysis of prophylactic residues focuses on the evaluation and identification of lubricants and constituents, primarily through gas chromatography or Fourier transform infrared spectroscopy. Though cost-effective methods, extensive sample preparation and destructive modes of analysis remain an area for improvement. As a result, the focus has since shifted to ambient ionization methods that offer adequate sensitivity and reduced sample preparation. The Liquid Microjunction Surface Sampling Probe (LMJSSP) is a versatile ambient ionization source that employs a probe that supports a continuously flushing droplet that extracts analytes when placed in contact with a surface. The analytes are aspirated into the mass spectrometer with a Venturi pressure. In this work we use the LMJSSP to analyse the trace transfer of condom lubricant to different types of fabric (cotton, cotton-spandex, and denim). Furthermore, we examine the sensitivity and storage conditions for the direct analysis method on different swab types (cotton, silicone, and foam). Additionally, Principal Component Analysis (PCA) and Maximally Collapsing Metric Learning (MCML) are utilized for visualization of differentiability of commercially available condom brands including Durex™ and Trojan™, and product subtypes. The results present an interesting multi-disciplinary approach of using a direct liquid extraction ambient ionization technique and machine learning to improve the overall workflow for the analysis of lubricants, swabs and fabrics. Machine learning algorithms were able to differentiate between inherent differences of Durex™ and Trojan™ condoms.

Direct Liquid Extraction and Ionization Techniques for Understanding Multimolecular Environments in Biological Systems (Secondary Publication).

A combination of direct liquid extraction using a small volume of solvent and electrospray ionization allows the rapid measurement of complex chemical components in biological samples and visualization of their distribution in tissue sections. This review describes the development of such techniques and their application to biological research since the first reports in the early 2000s. An overview of electrospray ionization, ion suppression in samples, and the acceleration of specific chemical reactions in charged droplets is also presented. Potential future applications for visualizing multimolecular environments in biological systems are discussed.

Direct Liquid Extraction and Ionization Techniques for Understanding Multimolecular Environment in Biological Systems

Direct Liquid Extraction and Ionization Techniques for Understanding Multimolecular Environment in Biological Systems

Extraction of dried oral fluid spots (DOFS) for the identification of drugs of abuse using liquid chromatography tandem mass spectrometry (LC-MS/MS)

Dried matrix spots (DMS) have been utilized as an alternative sample collection method for drug identification in different biological specimens in clinical and forensic toxicology scenarios. Oral fluid has demonstrated its potential to establish recent drug use in instances such as driving under the influence of drugs or workplace drug monitoring programs. Moreover, this matrix has become an excellent choice over invasive or prone to adulteration approaches, like blood or urine collection. The possibility of drying oral fluid on a paper substrate has open newer opportunities to facilitate sample distribution and analysis. In this study, a dried oral fluid spots (DOFS) method was used to investigate its performance for the analysis of a suite of drugs of toxicological interest. A direct liquid extraction from the paper substrate was assessed, and the detection and quantification were conducted using liquid chromatography-tandem mass spectrometry instrument. Amphetamine, methamphetamine, ketamine, benzoylecgonine, and mitragynine were selected as target drugs to evaluate the DOFS method. Figures of merit including selectivity, matrix effects, recovery (average of 82%, with the exception of mitragynine – 55%), process efficiency, LOQ (0.2 ng/mL), linearity carry over, intraday (3.2–8.4%) and inter-day precision (7.3–18.8%), accuracy (−1.0 to −12.2), and stability of DOFS samples (35 days) are presented. The DOFS method extraction capability was compared against a commercially available weak anion exchange (WAX-S) tips, and the results are presented herein. The method was also successfully applied to eight blind specimens to demonstrate proof of applicability and fit of purpose.

Direct liquid extraction surface analysis mass spectrometry of cell wall lipids from mycobacteria: Salt additives for decreased spectral complexity.

Lipids are important mycobacterium cell wall constituents; changes are linked with drug resistance. Liquid extraction surface analysis (LESA) enables direct sampling in a highly sensitive manner. Here we describe protocols for the analysis of lipids from bacterial colonies. Lipids form various adducts, complicating spectra. Salt additives were investigated to circumvent this problem. Chloroform:methanol mixtures were studied for lipid extraction and analysis by LESA-MS. The inclusion of (ESI-compatible) acetate salts of sodium, potassium or lithium in the extraction solvent was investigated. We report the detection of bacterial cell wall lipids from mycobacterial species using LESA for the first time. Sampling protocols were optimised for the use of volatile extraction solvents. The inclusion of acetate salt additives in the sampling solvent significantly reduces spectral complexity in comparison with no additives being used. LESA offers a sensitive technique for bacterial lipid phenotyping. The inclusion of an acetate salt in the sampling solvent drives adduct formation towards a specific adduct type and thus significantly reduces spectral complexity.

Visualization of Sampling and Ionization Processes in Scanning Probe Electrospray Ionization Mass Spectrometry.

Ambient sampling and ionization techniques based on direct liquid extraction and electrospray ionization are of great value for rapid analysis and mass spectrometry imaging. Scanning probe electrospray ionization (SPESI) enables the sampling and ionization of analyte molecules in a solid material using a liquid bridge and electrospray, respectively, from a single capillary probe. To further improve SPESI, it is essential to understand the dynamic behavior of nanoliter volumes of liquids during sampling and ionization. In this study, the dynamic formation and breakage of the liquid bridge and the subsequent electrospray ionization were investigated by measuring the displacement of the capillary probe using a new optical technique. Measurements revealed that both the time from the formation of the liquid bridge to its breakage and the time from the breakage of the liquid bridge to the detection of analyte ions were correlated with the physical properties of the solvent. It was also found that both of these times were positively correlated with the flow rate. These results will not only lead to the improvement of sampling and ionization efficiencies but also afford a greater understanding of the physicochemical properties of charged nanoliter volumes of liquids.

Simple quantification method for N-nitrosamines in atmospheric particulates based on facile pretreatment and GC-MS/MS

Nine N-nitrosamines (i.e., N-nitrosomethylamine, N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-nitrosodi-n-propylamine (NDPA), N-nitrosomorpholine (NMor), N-nitrosopyrrolidine (NPyr), N-nitrosopiperidine (NPip), N-nitorosodi-n-butylamine (NDBA), and N-nitrosodiphenylamine (NDPhA) in atmospheric PM2.5 collected in the fall season from an roadside site and a residential in Seoul, Korea have been analyzed using a newly developed method consisting of simple direct liquid extraction assisted by ultrasonication and subsequent quantification using a gas chromatography-triple quadrupole mass spectrometry (GC-TQMS). Excellent recovery values (92–100%) and method detection limits for the target compounds atmospheric PM samples could be achieved even without an evaporation step for sample concentration. The concentration of total N-nitrosamines in PM2.5 was ranged from 0.3 to 9.4 ng m−3 in this study; NDMA, NDEA, NDBA, NPyr, and NMor in PM2.5 were found to be the most frequently encountered compounds at the sampling sites. Since no industrial plant is located in Seoul, vehicle exhausts were considered major cause of the formation of nitrosamines in this study. The mechanisms how these compounds are formed and detected in the atmosphere are explained from the viewpoint of secondary organic aerosol. Considering the concentrations of N-nitrosamines and their associated potential health risks, a systematic monitoring of nitrosamines present in both ambient air and PM2.5 including seasonal and diurnal variations of selected sites (including potential precursor sources) should be carried out in the future. The proposed sample pretreatment method along with the analytical method will definitely help us perform the monitoring study.

Rapid sample classification using an open port sampling interface coupled with liquid introduction atmospheric pressure ionization mass spectrometry.

An "Open Access"-like mass spectrometric platform to fully utilize the simplicity of the manual open port sampling interface for rapid characterization of unprocessed samples by liquid introduction atmospheric pressure ionization mass spectrometry has been lacking. The in-house developed integrated software with a simple, small and relatively low-cost mass spectrometry system introduced here fills this void. Software was developed to operate the mass spectrometer, to collect and process mass spectrometric data files, to build a database and to classify samples using such a database. These tasks were accomplished via the vendor-provided software libraries. Sample classification based on spectral comparison utilized the spectral contrast angle method. Using the developed software platform near real-time sample classification is exemplified using a series of commercially available blue ink rollerball pens and vegetable oils. In the case of the inks, full scan positive and negative ion ESI mass spectra were both used for database generation and sample classification. For the vegetable oils, full scan positive ion mode APCI mass spectra were recorded. The overall accuracy of the employed spectral contrast angle statistical model was 95.3% and 98% in case of the inks and oils, respectively, using leave-one-out cross-validation. This work illustrates that an open port sampling interface/mass spectrometer combination, with appropriate instrument control and data processing software, is a viable direct liquid extraction sampling and analysis system suitable for the non-expert user and near real-time sample classification via database matching. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA.

Improving the Analysis of Anthocyanidins from Blueberries Using Response Surface Methodology

Background: Recent interest in the health promoting potential of anthocyanins points to the need for robust and reliable analytical methods. It is essential to know that the health promoting chemicals are present in juices and other products processed from whole fruit. Many different methods have been published using a wide variety of conditions for the hydrolysis of anthocyanins to anthocyanidins. Objective: To investigate the factors influencing the hydrolytic conversion efficiency. The optimum set of conditions will maximize the recovery of anthocyanidins. Method: Extraction procedure (freeze drying vs. direct liquid extraction), heating method (reflux vs. sealed vial), nitrogen purging and acid type were investigated. Response surface methodology was then used to find the optimum combination of incubation time, acid concentration and incubation temperature. Results: Anthocyanidin recovery can be maximized using this procedure: Freeze-dry homogenized fruit and extract with methanol:water:TFA, place 1 mL extract or juice in a test tube and add 440 µL 37% HCl, purge the tube with N2, seal with a PTFE lined cap, vortex, then heat at 99°C for 6.4 minutes. Filter the hydrolysate into an autosampler vial and analyze by UPLC immediately. Conclusion: Maximizing the recovery of anthocyanidins (by manipulating conditions in order to maximize peak areas) leads to a more accurate measure of the anthocyanidins present in blueberries.

Fully automated laser ablation liquid capture surface analysis using nanoelectrospray ionization mass spectrometry.

Laser ablation provides for the possibility of sampling a large variety of surfaces with high spatial resolution. This type of sampling when employed in conjunction with liquid capture followed by nanoelectrospray ionization provides the opportunity for sensitive and prolonged interrogation of samples by mass spectrometry as well as the ability to analyze surfaces not amenable to direct liquid extraction. A fully automated, reflection geometry, laser ablation liquid capture spot sampling system was achieved by incorporating appropriate laser fiber optics and a focusing lens into a commercially available, liquid extraction surface analysis (LESA(®))-ready Advion TriVersa NanoMate system. Under optimized conditions about 10% of laser-ablated material could be captured in a droplet positioned vertically over the ablation region using the NanoMate robot-controlled pipette. The sampling spot size area with this laser ablation liquid capture surface analysis (LA/LCSA) mode of operation (typically about 120 µm × 160 µm) was approximately 50 times smaller than that achievable by direct liquid extraction using LESA(®) (ca 1 mm diameter liquid extraction spot). The setup was successfully applied for the analysis of ink on glass and paper as well as the endogenous components in Alstroemeria Yellow King flower petals. In a second mode of operation with a comparable sampling spot size, termed laser ablation/LESA(®), the laser system was used to drill through, penetrate, or otherwise expose material beneath a solvent resistant surface. Once drilled, LESA(®) was effective in sampling soluble material exposed at that location on the surface. Incorporating the capability for different laser ablation liquid capture spot sampling modes of operation into a LESA(®)-ready Advion TriVersa NanoMate enhanced the spot sampling spatial resolution of this device and broadened the surface types amenable to analysis to include absorbent and solvent-resistant materials.

Direct Surface Analysis of Time-Resolved Aerosol Impactor Samples with Ultrahigh-Resolution Mass Spectrometry

Aerosol particles in the atmosphere strongly influence the Earth's climate and human health, but the quantification of their effects is highly uncertain. The complex and variable composition of atmospheric particles is a main reason for this uncertainty. About half of the particle mass is organic material, which is very poorly characterized on a molecular level, and therefore it is challenging to identify sources and atmospheric transformation processes. We present here a new combination of techniques for highly time-resolved aerosol sampling using a rotating drum impactor (RDI) and organic chemical analysis using direct liquid extraction surface analysis (LESA) combined with ultrahigh-resolution mass spectrometry. This minimizes sample preparation time and potential artifacts during sample workup compared to conventional off-line filter or impactor sampling. Due to the high time resolution of about 2.5 h intensity correlations of compounds detected in the high-resolution mass spectra were used to identify groups of compounds with likely common sources or atmospheric history.

Direct sampling and analysis from solid‐phase extraction cards using an automated liquid extraction surface analysis nanoelectrospray mass spectrometry system

Direct liquid extraction based surface sampling, a technique previously demonstrated with continuous flow and autonomous pipette liquid microjunction surface sampling probes, has recently been implemented as a liquid extraction surface analysis (LESA) mode on a commercially available chip-based infusion nanoelectrospray ionization (nanoESI) system. In the present paper, the LESA mode was applied to the analysis of 96-well format custom-made solid-phase extraction (SPE) cards, with each well consisting of either a 1 or a 2 mm diameter monolithic hydrophobic stationary phase. These substrate wells were conditioned, loaded with either single or multi-component aqueous mixtures, and read out using the commercial nanoESI system coupled to a hybrid triple quadrupole/linear ion trap mass spectrometer or a linear ion trap mass spectrometer. The extraction conditions, including extraction/nanoESI solvent composition, volume, and dwell times, were optimized in the analysis of targeted compounds. Limit of detection and quantitation as well as analysis reproducibility figures of merit were measured. Calibration data was obtained for propranolol using a deuterated internal standard which demonstrated linearity and reproducibility. A 10× increase in signal and cleanup of micromolar angiotensin II from a concentrated salt solution was demonstrated. In addition, a multicomponent herbicide mixture at ppb concentration levels was analyzed using MS(3) spectra for compound identification in the presence of isobaric interferences.

Liquid Microjunction Surface Sampling Coupled with High-Pressure Liquid Chromatography−Electrospray Ionization-Mass Spectrometry for Analysis of Drugs and Metabolites in Whole-Body Thin Tissue Sections

In this work, a commercially available autosampler was adapted to perform direct liquid microjunction (LMJ) surface sampling followed by a high-pressure liquid chromatography (HPLC) separation of the extract components and detection with electrospray ionization mass spectrometry (ESI-MS). To illustrate the utility of coupling a separation with this direct liquid extraction based surface sampling approach, four different organs (brain, lung, kidney, and liver) from whole-body thin tissue sections of propranolol dosed and control mice were examined. The parent drug was observed in the chromatograms of the surface sampling extracts from all the organs of the dosed mouse examined. In addition, two isomeric phase II metabolites of propranolol (an aliphatic and an aromatic hydroxypropranolol glucuronide) were observed in the chromatograms of the extracts from lung, kidney, and liver. Confirming the presence of one or the other or both of these glucuronides in the extract from the various organs was not possible without the separation. These drug and metabolite data obtained using the LMJ surface sampling/HPLC-MS method and the results achieved by analyzing similar samples by conventional extraction of the tissues and subsequent HPLC-MS analysis were consistent. The ability to directly and efficiently sample from thin tissue sections via a liquid extraction and then perform a subsequent liquid phase separation increases the utility of this liquid extraction surface sampling approach.

2081. Dioxane induction of nasal carcinomas

Nine N-nitrosamines (i.e., N-nitrosomethylamine, N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-nitrosodi-n-propylamine (NDPA), N-nitrosomorpholine (NMor), N-nitrosopyrrolidine (NPyr), N-nitrosopiperidine (NPip), N-nitorosodi-n-butylamine (NDBA), and N-nitrosodiphenylamine (NDPhA) in atmospheric PM2.5 collected in the fall season from an roadside site and a residential in Seoul, Korea have been analyzed using a newly developed method consisting of simple direct liquid extraction assisted by ultrasonication and subsequent quantification using a gas chromatography-triple quadrupole mass spectrometry (GC-TQMS). Excellent recovery values (92–100%) and method detection limits for the target compounds atmospheric PM samples could be achieved even without an evaporation step for sample concentration. The concentration of total N-nitrosamines in PM2.5 was ranged from 0.3 to 9.4 ng m−3 in this study; NDMA, NDEA, NDBA, NPyr, and NMor in PM2.5 were found to be the most frequently encountered compounds at the sampling sites. Since no industrial plant is located in Seoul, vehicle exhausts were considered major cause of the formation of nitrosamines in this study. The mechanisms how these compounds are formed and detected in the atmosphere are explained from the viewpoint of secondary organic aerosol. Considering the concentrations of N-nitrosamines and their associated potential health risks, a systematic monitoring of nitrosamines present in both ambient air and PM2.5 including seasonal and diurnal variations of selected sites (including potential precursor sources) should be carried out in the future. The proposed sample pretreatment method along with the analytical method will definitely help us perform the monitoring study.