Thermal Desorption Electrospray Ionization Mass Spectrometry Research Articles

Rapid Characterization of Undeclared Pharmaceuticals in Herbal Preparations by Ambient Ionization Mass Spectrometry for Emergency Care.

In Asia, some herbal preparations have been found to be adulterated with undeclared synthetic medicines to increase their therapeutic efficiency. Many of these adulterants were found to be toxic when overdosed and have been documented to bring about severe, even life-threatening acute poisoning events. The objective of this study is to develop a rapid and sensitive ambient ionization mass spectrometric platform to characterize the undeclared toxic adulterated ingredients in herbal preparations. Several common adulterants were spiked into different herbal preparations and human sera to simulate the clinical conditions of acute poisoning. They were then sampled with a metallic probe and analyzed by the thermal desorption-electrospray ionization mass spectrometry. The experimental parameters including sensitivity, specificity, accuracy, and turnaround time were prudently optimized in this study. Since tedious and time-consuming pretreatment of the sample is unnecessary, the toxic adulterants could be characterized within 60 s. The results can help emergency physicians to make clinical judgments and prescribe appropriate antidotes or supportive treatment in a time-sensitive manner.

Rapid screening of 15 highly toxic pesticide residues in Angelica sinensis decoctions by thermal desorption electrospray ionization mass spectrometry

ABSTRACT A decoction is the most common form of Chinese herbal medicine dosing. An Angelica sinensis decoction was qualitatively and semi-quantitatively analyzed for 15 highly toxic pesticide residues by thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS) with a triple quadrupole mass spectrometer in multiple reaction monitoring mode without pretreatment. The instrument response was optimal and sensitivity was highest with the following parameters: thermal desorption temperature, 300 °C; 0.1% formic acid aqueous solution-methanol (1:1,V:V) solvent; syringe pump flow rate, 150 μL/h; and sampler length, 5 cm. Good linearity was attained within the appropriate linear range with the detection limits ranging from 0.01–0.05 mg/L. The same positive sample was verified for QuEChERS pretreatment coupled with liquid chromatography tandem mass spectrometry, showing good agreement with TD-ESI/MS. The newly developed method was demonstrated to be a rapid, green, and efficient analytical method for screening 15 highly toxic pesticide residues in Angelica sinensis decoctions.

Avatar-like body imaging of dermal exposure to melamine in factory workers analyzed by ambient mass spectrometry.

Ambient mass spectrometry thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) can rapidly identify chemicals without pretreatment of biological samples. This study used a rapid semi-quantitative TD-ESI/MS screening technique for the probe skin sampling of melamine workers occupationally exposed to different ambient melamine concentrations to create avatar-like body images, which were then used to study temporal and dynamic changes in nephrotoxic melamine exposure. We enrolled four voluntary melamine workers from one factory, each from one of four worksites. Melamine exposure was highest in manufacturing and molding, followed by grinding and polishing, packing, and administration, the lowest. Skin samples were collected Friday (end-of-shift) and Monday (pre-shift). Early morning one-spot urine samples were also collected right after skin sampling. 2198 probe skin samples were collected and subjected to semi-quantitative TD-ESI/MS analyses of melamine chemical within 40h. After normalization, converted body image scores revealed exposure to be highest in the manufacturing worker on Friday and lowest in the administrative worker on Monday. The absolute differences (Friday minus Monday) of normalized body image scores were all significantly positive in each individual worker and across all four workers (permutation test, all p-values < 0.002). The slope estimates of the linear regression line between body image scores and urinary melamine levels were 0.81 (p-value=0.008). We concluded that this fast and non-invasive technique can potentially be used to study temporal and dynamic changes in exposure to occupational hazards. A future study of developing an automatic and reproducible TD-ESI/MS sampling platform is needed.

Rapid Characterization of Bacterial Lipids with Ambient Ionization Mass Spectrometry for Species Differentiation.

Ambient ionization mass spectrometry (AIMS) is both labor and time saving and has been proven to be useful for the rapid delineation of trace organic and biological compounds with minimal sample pretreatment. Herein, an analytical platform of probe sampling combined with a thermal desorption–electrospray ionization/mass spectrometry (TD-ESI/MS) and multivariate statistical analysis was developed to rapidly differentiate bacterial species based on the differences in their lipid profiles. For comparison, protein fingerprinting was also performed with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) to distinguish these bacterial species. Ten bacterial species, including five Gram-negative and five Gram-positive bacteria, were cultured, and the lipids in the colonies were characterized with TD-ESI/MS. As sample pretreatment was unnecessary, the analysis of the lipids in a bacterial colony growing on a Petri dish was completed within 1 min. The TD-ESI/MS results were further performed by principal component analysis (PCA) and hierarchical cluster analysis (HCA) to assist the classification of the bacteria, and a low relative standard deviation (5.2%) of the total ion current was obtained from repeated analyses of the lipids in a single bacterial colony. The PCA and HCA results indicated that different bacterial species were successfully distinguished by the differences in their lipid profiles as validated by the differences in their protein profiles recorded from the MALDI-TOF analysis. In addition, real-time monitoring of the changes in the specific lipids of a colony with growth time was also achieved with probe sampling and TD-ESI/MS. The developed analytical platform is promising as a useful diagnostic tool by which to rapidly distinguish bacterial species in clinical practice.

Molecular Mapping of Sebaceous Squalene by Ambient Mass Spectrometry.

Squalene (SQ), a highly unsaturated sebaceous lipid, plays an important role in protecting human skin. To better understand the role of SQ in clinical medicine, an efficient analytical approach is needed to comprehensively study the distribution of SQ on different parts of the skin. In this study, sebaceous lipids were collected from different epidermal areas of a volunteer with sampling probes. Thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) was then used to characterize the lipid species on the probes, and each TD-ESI/MS analysis was completed within a few seconds without any sample pretreatment. The molecular mapping of epidermal squalene on whole-body skin was rendered by scaling the peak area of the extracted ion current (EIC) of SQ based on a temperature color gradient, where colors were assigned to the 1357 sampling locations on a 3D map of the volunteer. The image showed a higher SQ distribution on the face than any other area of the body, indicating the role of SQ in protecting facial skin. The results were in agreement with previous studies using SQ as a marker to explore sebaceous activity. The novelty and significance of this work are concluded as two points: (1) direct and rapid detection of all major classes of sebaceous lipids, including the unsaturated hydrocarbons (SQ) and nonpolar lipids (e.g., cholesterol). The results are unique compared to other conventional and ambient ionization mass spectrometry methods and (2) this is the first study to analyze SQ distribution on the whole-body skin by a high-throughput approach.

Rapid Screening of β-Agonists in Animal Hair by Thermal Desorption Electrospray Ionization Mass Spectrometry

Even though the use of β-agonists in livestock has been banned in many countries, β-agonists abuse is still out of control owing to time-consuming and complicated determination techniques. This study applied ambient thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS) as a new strategy for rapidly screening seven β-agonists. As it does not require pretreatment, this method allows on-site and real-time detection. Samples were collected directly using a simple metal probe. Analytes on the probe were desorbed and ionized by TD-ESI, after which analyte ions were detected using a triple quadrupole mass analyser. The results showed that a thermal desorption temperature of 320°C and nebulizer pressure of 3 psi demonstrated the highest sensitivity. Excellent linear relationships were obtained in concentrations ranging from 10 to 400 μg/kg. The limit of detection of the method was 1-10 μg/kg with RSDs of 7.2-14.6%. A positive sample was verified using HPLC coupled with triple quadrupole tandem mass spectrometry, consistent with the results from TD-ESI/MS. This method was the first to apply TD-ESI/MS to rapid analyse β-agonists in livestock hair and was proven to be accurate, fast, and environmentally friendly. Because qualitative screening for each analysis was completed within approximately 1 min, the method could contribute to preventing non-compliance in the flow of animal-derived food to the market. This method was a promising method for the rapid screening of β-agonists in livestock hair at any time of breeding without imposing any harm to animal which proven to be a rapid, in situ, and non-destructive detection technique without any pretreatment.

Multiple solid phase microextraction combined with ambient mass spectrometry for rapid and sensitive detection of trace chemical compounds in aqueous solution

Multiple solid phase microextraction (mSPME) combined with thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) was developed to rapidly characterize trace analytes in aqueous solution. A number of commercial available SPME fibers (from 2 to 10 fibers) were simultaneously used for extracting the analytes in solution. The fibers were then bundled together on a holder and subjected for the ambient mass spectrometric analysis. Good linearity for calibration (R2 = 0.9995) and low limit of quantification (<1 ppb) were achieved by using 10 SPME fibers coated with polyacrylate (PA) to extract bisphenol A. It was also found that the analyte signals increased with the number of SPME fibers for extraction. Uncontroversial, a shorter extraction time was required by using mSPME to reach the same level of analyte signal as that by using single SPME fiber for a longer extraction time. Trace bisphenol A (4–20 ppb) in the polycarbonate (PC) baby milk bottles was rapidly detected using mSPME-TD-ESI/MS and the analysis was completed within 1 min. The use of multiple SPME fibers coated with different materials enable the concentration of different type of analytes in the solution. Ibuprofen, bisphenol A (BPA), and 4-n-nonylphenol (4-n-NP) were simultaneously detected by using PA and polydimethylsiloxane (PDMS) coated fibers for extraction.

Using ambient mass spectrometry to explore the origins of phthalate contamination in a mass spectrometry laboratory

Phthalates are known endocrine disruptors that can have adverse effects on human hormonal balance and development. Phthalates are semi-volatile chemical compounds, thus they can continuously leach from phthalate-containing objects and pollute the environments such as offices or laboratories, where workers in these spaces can inhale potentially harmful amounts of phthalates. Identifying and removing phthalate-contaminated objects from these indoor environments can effectively eliminate exposure to these environmental hormones. However, as of now, it is highly impractical to perform a large-scale screening of phthalate-containing objects using conventional analytical techniques which are usually time- and labor-intensive. In this study, thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS) combined with probe sampling was used to screen phthalates on all non-metallic objects in a mass spectrometry (MS) laboratory. Due to sample pre-treatment was unnecessary and there was no limitation of sampling on sample's shape, size, and material, screening of phthalates on an object using this ambient mass spectrometric approach was completed within 30s, which enable sufficient and high-throughput screening. Phthalate signals of di(2-ethylhexyl)phthalate (DEHP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were qualitatively detected on the surfaces of the filters of air conditioners and air purifiers and laboratory door, indicating there was a possibility of phthalates contamination in the studying area. Other screened objects in the laboratory included the ceiling, wall, floor, chairs, benches, pipes, mechanical vacuum pump tubes, and some personal belongings, all of which contained phthalates. Among them, floor and mechanical vacuum pump tubes contained high concentration of DEHP, DINP and DIDP, suggesting they were the main sources of phthalate contamination in the MS laboratory.

Direct and rapid characterization of illicit drugs in adulterated samples using thermal desorption electrospray ionization mass spectrometry

Foods and drinks have been adulterated with illicit drugs to facilitate criminal activities. Unfortunately, conventional analytical methods are incapable of rapidly characterizing these drugs in samples, as serious interferences from sample matrices must be removed through tedious and time-consuming pretreatment. Ambient ionization mass spectrometry (AMS) generally does not require sample pretreatment and is thus a suitable tool for directly and rapidly detecting illicit drugs in samples in different physical states. In this study, thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS), an AMS technique, was utilized to efficiently characterize illicit drugs spiked in samples including drinks, powders, and jelly candies. To perform sensitive analysis, the mass analyzer was operated in multiple reaction monitoring mode to monitor the molecular and fragment ions of the target analytes. The time required to complete a typical TD-ESI/MS analysis was less than 30 s. The limits of detection (LODs) for illicit drugs were found to be 100 ppb in drinks, 100–1000 ppb in instant powders, and 1.3–6.5 ng/mm2 on stamp surfaces. FM2 and nitrazepam laced in the inner layer of a jelly candy were detected by TD-ESI/MS, showcasing the advantage of the technique for direct and rapid analysis as opposed to conventional methods.

High-throughput screening of phthalate-containing objects in the kindergartens by ambient mass spectrometry

High-throughput screening of plastic products in children's living environment is necessary to identify phthalate-containing objects for the concern of public health and safety. A novel strategy of probe collecting technique combined with ambient mass spectrometry was developed to carry out the large-scale sample analysis. Analytes from the surface of approximately 500 objects each in two kindergartens in Taiwan were collected using the same number of the metallic probes. After being delivered to laboratory, the analytes on the probes were analyzed with thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS). As sample pretreatment was unnecessary, the analysis of phthalates on a probe was completed within 30 s enabling high-throughput screening of a large number of objects. All procedure including sampling and TD-ESI/MS analysis together with report writing for a kindergarten was completed in one day. A reasonable relative standard deviation (<15.6%) was obtained from replicate analyses of phthalate standards. Single-point calibration was used to perform semi-quantitative analysis, and results were validated by liquid chromatography/mass spectrometry (LC/MS). It was found that 20–40% of the objects in two kindergartens contained greater than low-level (>2 ng) of phthalates and 40–60% of the objects in the kindergartens contained more than one kind of phthalate.

Point-of-care identification of organophosphates in gastric juice by ambient mass spectrometry in emergency settings

BackgroundFor emergency management, it is important to promptly identify the organophosphate ingested by self-poisoning patients since different organophosphates cause intoxication through different mechanisms and require different therapeutic strategies. This study aimed at the development of a point-of-care ambient mass spectrometric approach for rapid identification of organophosphate(s) in gastric juice for emergency management. MethodsSix organophosphate insecticides that are commonly ingested by self-poisoning patients in Taiwan were examined. The sample solutions were prepared and diluted with human gastric juice. A direct metallic probe was dipped and removed immediately from the sample solution. The probe was then inserted into the thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) to detect the analyte on the probe. ResultsSince no pretreatment of the specimen was required, the sampling processes followed by thermal desorption-electrospray ionization and mass spectrometric analysis of the organophosphate in the gastric juice were completed within 30 s. The detection limit of the organophosphates is at the 10–100 parts per billion level. Good linearity was observed between the corresponding changes in mass spectrometric signal intensities and the changes of organophosphate concentrations within the range of 5–1000 parts per billion. The high efficiency of this ambient mass spectrometric platform was further confirmed when a real sample of the drained gastric lavage fluid of a patient who suffered from ingestion of chlorpyrifos was collected in the emergency room and tested with this cutting-edge technique. ConclusionsThe results suggested that TD-ESI/MS is promising in promptly providing toxicological information to assist succeeding medical management in an emergency room.

Solid phase microextraction combined with thermal-desorption electrospray ionization mass spectrometry for high-throughput pharmacokinetics assays

Labor- and time-intensive sample preparation and liquid chromatography mass spectrometry (LC-MS) analysis are required for traditional pharmacokinetics (PK) studies. In order to simplify and accelerate the analytical process of the PK study, solid phase microextraction (SPME) combined with thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) was developed for rapid characterization of trace drug in biological fluids. Methylphenidate in plasma was extracted and concentrated by direct immersion SPME using fused-silica fibers coated with polydimethylsiloxane. The analytes on the SPME fiber were then characterized by TD-ESI/MS. Matrix-matched calibration with multiple reaction monitoring analysis was conducted to quantify methylphenidate. A linear calibration curve was constructed over a concentration range of 0.2–25 ng mL−1 (r = 0.997). The quantitative results obtained by SPME-TD-ESI/MS were validated by LC-MS/MS. The average relative error for both methods was found to be −5.3%. As a viable alternative to LC-MS, SPME-TD-ESI/MS enables simple, rapid, and high-throughput analysis of drugs in plasma. The developed approach is particularly beneficial to PK studies for a very small sample volume (10 μL) is needed, the extraction time is as short as 3 min, and the detection time is less than 30 s.

Using thermal desorption electrospray ionization mass spectrometry to rapidly determine antimicrobial preservatives in cosmetics.

Characterization and quantification of permitted preservatives are important inspections to prevent the overuse of preservatives in authentic formulations. However, the complexity of sample matrices makes preservative determination in cosmetics a tedious process. A rapid analytical strategy to identify preservatives would insure large numbers of products are in compliance with government regulations. Thermal desorption electrospray ionization mass spectrometry (TD-ESI-MS) was used to directly detect preservative compounds in authentic formulations without sample pretreatment. The technique employs a metal probe, which was configured for sampling cosmetics in their original states and was inserted in a closed preheated oven to thermally desorb analytes. The desorbed analytes were then carried by a nitrogen gas stream into an ESI plume, where the formed ions were subsequently detected by the mass analyzer. The TD-ESI mass and tandem mass spectra of different classes of preservative standards were rapidly obtained, and the limits of detection were far below the legal limit of their respective concentrations. The preservatives were also directly detected in different types of authentic formulations in the absence of sample preparation, and within a few seconds per sample. Calibration curves for preservatives in four common formulations yielded good linearity in the regulation-allowed range. Due to its sensitivity, short analysis time, repeatability, and quantitative ability, TD-ESI-MS may serve as a suitable tool for large-scale screening of cosmetic preservatives to assure product safety. Copyright © 2016 John Wiley & Sons, Ltd.

Rapid identification of pesticides in human oral fluid for emergency management by thermal desorption electrospray ionization/mass spectrometry.

Self-poisoning with pesticides accounts for approximately one-third of all suicides worldwide. To expedite rescue in the emergency department, it is essential to develop a point-of-care analytical method for rapid identification of ingested pesticides. In this study, five of the most common pesticides ingested by self-poisoning patients in Taiwan were analyzed from oral fluid samples. Pesticide-oral fluid mixtures were applied on a cotton swab and then transferred into methanol. A metallic probe was used to sample the methanol solution for subsequent thermal desorption-electrospray ionization mass spectrometry analysis. Altogether, pesticide sampling, transfer, desorption, ionization, and detection took less than 1 min. The reproducibility of this method (n = 6) was shown in the observed low-relative standard deviation (<7%) in the detection of pesticide in oral fluid. The detection limits of the pesticides in oral fluid obtained from four human subjects by thermal desorption-electrospray ionization mass spectrometry were between 1-10 ppb with relative standard deviation 10.7%. Moreover, in this study, linear responses of five pesticides in oral fluid with concentrations between 1 ppb-1 ppm (R2 between 0.9938 and 0.9988) were observed. As the whole analytical process is extremely short, this technique allows for early non-invasive point-of-care identification of pesticides in the oral fluid of self-poisoning patients in the emergency room, providing important toxicological information for decision-making during critical resuscitation.

Rapid identification of pesticides in human oral fluid for emergency management by thermal desorption electrospray ionization/mass spectrometry

The World Health Organization acknowledges that pesticide self-poisoning is among the most frequently used methods of suicide worldwide. It is therefore of the highest importance to promptly identify the type of pesticides ingested by self-poisoning patients because different pesticides cause intoxication through different mechanisms, requiring different therapeutic strategies, precautions against contraindicating actions, directions of clinical course monitoring and predictions of prognosis. In this perspective Special Feature, Pr. Bai-Hsiun Chen (Laboratory Medicine and Pediatrics, College of Medicine, Kaohsiung Medical University, Taiwan) and colleagues propose a point-of-care analytical method for rapid identification of five residual pesticides in oral fluid using thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS). This non-invasive approach can expedite emergency care and may provide important toxicological information for decision-making during critical resuscitation.

Rapid screening of residual pesticides on fruits and vegetables using thermal desorption electrospray ionization mass spectrometry.

Conventional mass spectrometry is encumbered by laborious and inconvenient sample pretreatment. Ambient thermal desorption electrospray ionization mass spectrometry (TD-ESI-MS) is most noted for its rapid, simple, and sensitive detection capabilities. In this study, TD-ESI-MS was used to rapidly characterize residual pesticides on the surfaces of fruits and vegetables. A direct sampling probe was used to obtain analytes from sample surfaces. MS and MS/MS analyses were performed on fruits and vegetables via TD-ESI-MS. External calibration curves and reproducibility tests were performed using liquid pesticide standards. Pesticide decay and distribution on samples was studied, as well as the removal of residual pesticides via soaking in water or detergent baths. Since sample pretreatment was unnecessary, an analysis was completed in approximately 15 s or less, with no visible sample damage. Mass spectra were obtained for 22 pesticides. Linear calibrations (R(2) from 0.9414-0.999) had limits of detection as low as 0.5 µg·L(-1), with satisfactory reproducibilities for liquids and solids. Pesticides on sample surfaces decayed over 2 weeks under ambient conditions. Residual pesticides localized at the fruit peel. Detergent baths removed more pesticide than water baths. TD-ESI-MS was used to rapidly screen residual pesticides in liquids and solids. Pesticides were found on fruits and vegetables, where the decay, distribution, and removal of pesticides on samples were also explored. Due to short analysis times, the technique allows for high-throughput analyses for applications in food and environmental safety.