Thermal desorption ambient ionization mass spectrometry for emergency toxicology.

In the emergency department, it is important to rapidly identify the toxic substances that have led to acute poisoning because different toxicants or toxins cause poisoning through different mechanisms, requiring disparate therapeutic strategies and precautions against contraindicating actions, and diverse directions of clinical course monitoring and prediction of prognosis. Ambient ionization mass spectrometry, a state-of-the-art technology, has been proved to be a fast, accurate, and user-friendly tool for rapidly identifying toxicants like residual pesticides on fruits and vegetables. In view of this, developing an analytical platform that explores the application of such a cutting-edge technology in a novel direction has been initiated a research program, namely, the rapid identification of toxic substances which might have caused acute poisoning in patients who visit the emergency department and requires an accurate diagnosis for correct clinical decision-making to bring about corresponding data-guided management. This review includes (i) a narrative account of the breakthrough in emergency toxicology brought about by the advent of ambient ionization mass spectrometry and (ii) a thorough discussion about the clinical implications and technical limitations of such a promising innovation for promoting toxicological tests from tier two-level to tier one level.

A low-cost eco-friendly fast drug extraction (FaDEx) technique for environmental and bio-monitoring of psychoactive drug in urban water and sports-persons' urine samples.

Nicotine is the most prominent psychoactive/addictive chemical substance consumed worldwide among young players in team sports. Moreover, urinary nicotine discharge and nicotine-based products disposal in environmental waters has been unavoidable in recent years. Therefore, sensitive monitoring of nicotine content in environmental waters and human urine samples is essential. In this study, we developed a miniaturized novel green, low-cost, sensitive, in-syringe-based semi-automated fast drug extraction (FaDEx) protocol coupled with gas chromatography-flame ionization detection (GC-FID) for the efficient environmental and bio-monitoring of nicotine in aqueous samples. The FaDEx method consists of two steps; firstly, the target analyte was extracted using dimethyl carbonate (a green solvent) and extraction salts. After that, the extraction solvent was passed automatically through the solid-phase extraction cartridge at a constant flow rate for the cleanup process to achieve the sensitive nicotine analysis by GC-FID. Under optimized experimental conditions, the developed method showed excellent linearity over the concentration ranges between 20-2000 ng mL-1 with a correlation coefficient >0.99. The detection and quantification limits were 4 and 20 ng mL-1, respectively. The presented method was applied to monitor and assess nicotine exposure in sports-persons' urine and environmental water samples. The method accuracy and precision in terms of relative recovery and relative standard deviation (for triplicate analysis) were 85.4-110.2% and ≤8%, respectively. Finally, the impact of our procedure on the environment from a green analytical chemistry view was assessed using a novel metric system called AGREE, and obtained the greenness score of 0.87, indicating its an efficient alternative green analytical protocol for routine environmental and bio-monitoring of nicotine in environmental and biological samples.

Novel fast pesticides extraction (FaPEx) strategy coupled with UHPLC-MS/MS for rapid monitoring of emerging pollutant fipronil and its metabolite in food and environmental samples.

In this work, we demonstrated a new, environmental-friendly and effective sample preparation strategy named 'in-syringe-assisted fast pesticides extraction (FaPEx)' technique coupled with LC-MS/MS for the rapid identification and monitoring of emerging pollutant fipronil and its metabolite fipronil sulfone in chicken egg and environmental soil samples. FaPEx strategy comprising of two simple steps. Firstly, the sample was placed in the syringe and extracted using low-volume acetonitrile with NaCl and anhydrous MgSO4 salts. Secondly, the extractant was passed through in-syringe-based solid-phase extraction (SPE) kit containing cleanup sorbents and salt combinations (C18, primary secondary amine, and anhydrous MgSO4) for the cleanup process. Then, the obtained clean extractant was injected into LC-MS/MS for the quantification of target analytes. Various important parameters influencing the FaPEx performances, such as solvent type, salt type, salt amount, sorbent type, and amount, were examined and optimized. The method validation results showed excellent linearity with high correlation coefficients were ≥ 0.99. The estimated LODs were between 0.05-0.07 µg/kg, and LOQs ranged between 0.1-0.25 µg/kg for target analytes in both egg and soil sample matrices, and precision values were ≤7.90%. The developed method was applied to commercial chicken egg samples and environmental soil samples analysis. Spiked recoveries ranged between 88.75-110.91% for egg samples with RSDs ≤7.42% and 82.47-107.46% for soil samples with RSDs <7.37%. These results proved that the developed sample preparation method is a simple, fast, green, low-cost, and efficient method for the analysis of fipronil and its metabolites in food and environmental samples. Thus, this method can be applied as an alternative analytical methodology in routine and standard food and environmental testing laboratories.

Rapid Identification and Analysis of Ochratoxin-A in Food and Agricultural Soil Samples Using a Novel Semi-Automated In-Syringe Based Fast Mycotoxin Extraction (FaMEx) Technique Coupled with UHPLC-MS/MS.

In this work, a fast mycotoxin extraction (FaMEx) technique was developed for the rapid identification and quantification of carcinogenic ochratoxin-A (OTA) in food (coffee and tea) and agricultural soil samples using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection. The FaMEx technique advancement is based on two plastic syringes integrated setup for rapid extraction and its subsequent controlled clean-up process. In the extraction process, a 0.25-g sample and extraction solvent were added to the first syringe barrel for the vortex-based extraction. Then, the extraction syringe was connected to a clean-up syringe (pre-packed with C18, activated carbon, and MgSO4) with a syringe filter. Afterward, the whole set-up was placed in an automated programmable mechanical set-up for controlled elution. To enhance FaMEx technology performance, the various influencing sample pretreatment parameters were optimized. Furthermore, the developed FaMEx method indicated excellent linearity (0.9998 and 0.9996 for coffee/tea and soil) with highly sensitive detection (0.30 and 0.29 ng/mL for coffee/tea and soil) and quantification limits (1.0 and 0.96 for coffee/tea and soil), which is lower than the toxicity limit compliant with the European Union regulation for OTA (5 ng/g). The method showed acceptable relative recovery (84.48 to 100.59%) with <7.34% of relative standard deviation for evaluated real samples, and the matrix effects were calculated as <-13.77% for coffee/tea and -9.7 for soil samples. The obtained results revealed that the developed semi-automated FaMEx/UHPLC-MS/MS technique is easy, fast, low-cost, sensitive, and precise for mycotoxin detection in food and environmental samples.

Facile analysis of mycotoxin in coffee and tea samples using a novel semi-automated in-syringe based fast mycotoxin extraction (FaMEx) technique coupled with direct-injection ESI-MS/MS analysis.

Identifying the risk of ochratoxin A in our daily food has become fundamental because of its toxicity. In this work, we report a novel semi-automated in-syringe-based fast mycotoxin extraction (IS-FaMEx) technique coupled with direct-injection electrospray-ionization tandem mass spectrometer (ESI-MS/MS) detection for the quantification of ochratoxin A in coffee and tea samples. Under the optimized conditions, the results reveal that the developed method's linearity was more remarkable, with a correlation coefficient of > 0.999 and > 92% extraction recovery with a precision of 6%. The detection and quantification limits for ochratoxin A were 0.2 and 0.8 ng g-1 for the developed method, respectively, which is lower than the European Union regulatory limit of toxicity for ochratoxin-A (5 ng g-1) in coffee. Furthermore, the newly developed modified IS-FaMEx-ESI-MS/MS exhibited lower signal suppression of 8% with a good green metric score of 0.64. In addition, the IS-FaMEx-ESI-MS/MS showed good extraction recovery, matrix elimination, good detection, and quantification limits with high accuracy and precision due to the fewer extraction steps with semi-automation. Therefore, the presented method can be applied as a potential methodology for the detection of mycotoxins in food products for food safety and quality control purposes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05733-z.

Thermogravimetry combined with electrospray and atmospheric pressure chemical ionization mass spectrometry for characterization of synthetic polymers.

RATIONALE: Thermogravimetry (TG) combined with electrospray and atmospheric chemical ionization (ESI+APCI) mass spectrometry (MS) was developed to rapidly characterize thermal decomposition products of synthetic polymers and plastic products. The ESI-based TG-MS method is useful for characterizing thermally labile, nonvolatile, and polar compounds over an extensive mass range; and the APCI-based TG-MS counterpart is useful for characterizing volatile and nonpolar compounds. Both polar and nonpolar compounds can be simultaneously detected by ESI+APCI-based TG-MS. METHODS: Analytes with different volatility were produced from TG operated at different temperatures, which were delivered through a heated stainless-steel tube to the ESI+APCI source where they reacted with the primary charged species generated from electrospray and atmospheric pressure chemical ionization (ESI+APCI) of solvent and nitrogen. The analyte ions were then detected by an ion trap mass spectrometer. RESULTS: A semi-volatile PEG 600 standard was used as the sample and protonated and sodiated molecular ions together with adduct ions including [(PEG)n + 15]+ , [(PEG)n + 18]+ , and [(PEG)n + 29]+ were detected by TG-ESI+APCI-MS. The technique was further utilized to characterize thermal decomposition products of nonvolatile polypropylene glycol (PPG) and polystyrene (PS) standards, as well as a PS-made water cup and coffee cup lid. The characteristic fragments of PPG and PS with mass differences of 58 and 104 between respective ion peaks were detected at the maximum decomposition temperature (Tmax ). CONCLUSIONS: The information obtained from the TG-ESI+APCI-MS analysis is useful in rapidly distinguishing different types of polymers and their products. In addition, the signals of the additives in the polymer products, including antioxidants and plasticizers, were also detected before the TG temperature reached Tmax .

Thin layer chromatography/desorption flame-induced atmospheric pressure chemical ionization/mass spectrometry for the analysis of volatile and semi-volatile mixtures.

Flame-induced atmospheric pressure chemical ionization (FAPCI) has been used to directly characterize chemical compounds on a glass rod and drug tablet surfaces. In this study, FAPCI was further applied to interface thin layer chromatography (TLC) and mass spectrometry (MS) for mixture analysis. METHODS: A micro-sized oxyacetylene flame was generated using a small concentric tube system. Hot gas flow and primary reactive species from the micro-flame were directed toward a developed TLC gel plate to thermally desorb and ionize analytes on the gel surface. The resulting analyte ions subsequently entered the MS inlet for detection. RESULTS: A 1-1.5-mm-wide light-brown line was observed on the TLC plate after the desorption FAPCI/MS (DFAPCI/MS) analysis, revealing that the gel surface withstood a high temperature from the impact of the micro-flame. Volatile and semi-volatile chemical compounds, including amine and amide standards, drugs, and aromatherapy oils, were successfully desorbed, ionized, and detected using this TLC/DFAPCI/MS. The limit of detection of TLC-DFAPCI/MS was determined to be 5 ng/spot for dibenzylamine and ethenzamide. CONCLUSIONS: TLC/DFAPCI/MS is one of the simplest TLC-MS interfaces showing the advantages such as low costs and an easy set up. The technique is useful for characterizing thermally stable volatile and semi-volatile compounds in a mixture.

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.

Associations of dermal diethyl phthalate level with changes in lung function test value mediated by absolute eosinophil count: A panel study of adults in southern Taiwan.

Phthalate concentrations in indoor and outdoor dust are associated with respiratory disease. Both immunoglobulin E (IgE) and eosinophil count are associated with airway inflammation from exposure to environmental allergens. Dermal phthalate level can be used as a matrix for assessing personal exposure through direct absorption from the air, particle deposition, or contact with contaminated products. However, the association between dermal phthalate level and changes in lung function test values, as mediated by immunological response, remains unclear. In total, 237 adults in southern Taiwan were recruited. Spirometry measurements (in L) of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were taken on visits 1 (2016-2018) and 2 (2019). Dermal phthalate level, absolute eosinophil count, and IgE level were recorded on visit 1. Mean changes in FVC and FEV1 decrease pear year, as determined through pairwise comparisons, were significant (diffFVCper year: -0.46, 95% CI: -0.51, -0.41; p < 0.001; diffFEV1per year: -0.37, 95% confidence interval [CI]: -0.41, -0.34; p < 0.001). For FEV1 decrease, log-unit increases in dermal diethyl phthalate (DEP) were positively associated with diffFEV1per year (ß = 0.096; 95% CI: 0.042, 0.150; p = 0.001) and negatively associated with absolute eosinophil count (ß= -0.201; 95% CI: -0.380, -0.023; p= 0.027). Log-unit increases in absolute eosinophil count were negatively associated with diffFEV1per year (ß= -0.109; 95% CI: -0.150, -0.068; p < 0.001). Absolute eosinophil count mediated 19.70% of the association between dermal DEP level and diffFEV1per year. For FVC decrease, log-unit increases in dermal DEP were positively associated with diffFVCper year (ß = 0.095; 95% CI: 0.035, 0.155; p = 0.002) and negatively associated with absolute eosinophil count (ß = -0.243; 95% CI: -0.427, -0.060; p = 0.010). Log-unit increases in absolute eosinophil count were negatively associated with diffFVCper year (ß= -0.122; 95% CI: -0.168, -0.076; p < 0.001). Absolute eosinophil count mediated 29.98% of the association between dermal DEP level and diffFVCper year. The results suggest that dermal DEP level is positively associated with changes in lung function test values and is mediated by absolute eosinophil count.

Characterization of Potential Protein Biomarkers for Major Depressive Disorder Using Matrix-Assisted Laser Desorption Ionization/Time-of-Flight Mass Spectrometry.

Matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) mass spectrometry is a sensitive analytical tool for characterizing various biomolecules in biofluids. In this study, MALDI-TOF was used to characterize potential plasma biomarkers for distinguishing patients with major depressive disorder (MDD) from patients with schizophrenia and healthy controls. To avoid interference from albumin-the predominant protein in plasma-the plasma samples were pretreated using acid hydrolysis. The results obtained by MALDI-TOF were also validated by electrospray ionization-quadrupole time-of-flight (ESI-QTOF) mass spectrometry. The analytical results were further treated with principal component analysis (PCA), hierarchical clustering analysis (HCA), and receiver operating characteristic (ROC) curve analysis. The statistical analyses showed that MDD patients could be distinguished from schizophrenia patients and healthy controls by the lack of apolipoprotein C1 (Apo C1), which, in fact, was detected in healthy controls and schizophrenia patients. This protein is suggested to be a potential plasma biomarker for distinguishing MDD patients from healthy controls and schizophrenia patients. Since sample preparation for MALDI-TOF is very simple, high-throughput plasma apolipoprotein analysis for clinical purposes is feasible.

Rapid identification of organophosphorus pesticides on contaminated skin and confirmation of adequate decontamination by ambient mass spectrometry in emergency settings.

RATIONALE: Dermal exposure to pesticides may cause severe intoxication and even result in a fatal outcome. To expedite rescue in the emergency department, it is mandatory to develop a point-of-care analytical method for immediate identification of pesticides on the skin of exposed personnel, and to perform immediate dermal decontamination to prevent further harm and optimize the chance for full clinical recovery. METHODS: Four of the most commonly used highly toxic pesticides that contaminate the skin were rapidly characterized by thermal desorption electrospray ionization mass spectrometry. The technique was also applied to confirm the completeness of pesticide decontamination from the skin. Pesticide sampling, desorption, ionization, and detection altogether took less than 30 s. In addition, different fabrics of protective garments worn by farmers were assessed with this efficient ambient mass spectrometric technique for their protective capabilities against dermal exposure to pesticides, and scanning electron microscopy was used to observe their different microstructures. The decontaminating efficacies of different cleansing agents for these skin contaminants were also evaluated by this technical platform. RESULTS: The repeatability of this method had a low relative standard deviation (<22%) for the detection of pesticides on the surface of swine skin. The detection limits of the pesticides in solution were found to be in the range of 3-20 ng/mL. Linearity was observed between the signal intensities and the concentrations of the four pesticides in solution within the range of 50 ng/mL to 50 µg/mL (R2 between 0.9921 and 0.9966). In addition, it was found that PVC fabric is optimal in preventing skin contamination by fenthion and detergent had the best efficiency for fenthion decontamination. CONCLUSIONS: Since the whole analytical process is extremely fast, this technique allows early point-of-care identification of contaminating pesticides on the skin of exposed patients in the emergency room, as well as rapid assessment of the adequacy of decontamination.

Rapid quantification of acetaminophen in plasma using solid-phase microextraction coupled with thermal desorption electrospray ionization mass spectrometry.

RATIONALE: Solid-phase microextraction coupled with thermal desorption electrospray ionization tandem mass spectrometry (SPME-TD-ESI-MS/MS) is proposed as a novel method for the rapid quantification of acetaminophen in plasma samples from a pharmacokinetics (PK) study. METHODS: Traces of acetaminophen were concentrated on commercial fused-silica fibers coated with a polar polyacrylate (PA) polymer using direct immersion SPME. No agitation, heating, addition of salt, or adjustment of the pH of the sample solution was applied during the extraction. Any acetaminophen absorbed on the SPME fibers was subsequently desorbed and detected by TD-ESI-MS/MS. RESULTS: Parameters of the absorption, sensitivity, reproducibility, and linearity for the SPME-TD-ESI-MS/MS method were evaluated. The time required to complete a TD-ESI-MS/MS analysis was less than 30 seconds. Matrix-matching calibration was performed to calculate the concentration of acetaminophen in the sample. A linear calibration curve with a concentration range of 100-10,000 ng/mL was constructed to calculate the quantity of acetaminophen. The SPME-TD-ESI-MS quantification results for acetaminophen in plasma were in good agreement with those obtained by the conventional LC/MS/MS method. CONCLUSIONS: With the proposed method, a 10-min SPME time was enough to achieve the lower limit of quantitation (i.e. 100 ng/mL) and for a complete PK profiling of acetaminophen. A shorter extraction time could be achieved by applying agitation, heating, adding salt, or adjusting the pH of the sample solution to enhance analyte absorption efficiency. The time required to detect acetaminophen on the SPME fiber was less than 30 s, allowing the rapid quantification of acetaminophen in plasma with good accuracy.

Ambient mass spectrometry for rapid diagnosis of psychoactive drugs overdose in an unstable patient.

A 25-year-old man suffered from consciousness change was sent to our emergency department by friends who reported that they were not sure what had happened to him. Physical examination revealed bilateral pupils dilatation, lethargy, slurred speech, and ataxia. Computer-aided tomographic scan of the brain revealed no definite evidence of intracranial lesions. Routine laboratory tests revealed total physiological turmoil. Despite immediate commencement of aggressive treatment, the patient's condition deteriorated long before the traditional drug screen provided an answer for the identities of the multiple drugs overdose. It ended up with the need for cardiopulmonary resuscitation, but in vain. At the end of the tragic event, under the suggestion of a colleague, a portion of the patient's urine specimen was sent to our university esoteric laboratory for rapid analysis by means of a newly-developed thermal desorption-electrospray ionization-mass spectrometry. Ketamine, 3,4-methylenedioxymethamphetamine, and 3,4-methylenedioxyamphetamine were identified in the urine sample within 30s. Conventional toxicological testing techniques like gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry are currently used for identifying abused drugs. One concern is their time-consuming sample pretreatment which leads to relatively low efficiency in terms of turnaround time for revealing the identity of the consumed drugs particularly when the patients are severely overdosed. We learned a lesson from this case that a more efficient toxicological identification technique is essential to expedite the process of emergency care when the patients are so heavily overdosed that they are under critical life-threatening conditions.

Rapid characterization of trace aflatoxin B1 in groundnuts, wheat and maize by dispersive liquid-liquid microextraction followed by direct electrospray probe tandem mass spectrometry.

RATIONALE: Aflatoxins are poisonous and cancer-related chemical compounds commonly found in crops and plants. Aflatoxin B1 is the most toxic compound among aflatoxins and has been classified as group 1 carcinogenic to humans, especially in liver cancer. Herein, an ambient mass spectrometric method was developed for rapid characterization of trace aflatoxin B1 in peanuts. METHODS: Direct electrospray probe tandem mass spectrometry (DEP-MS/MS) was used to detect aflatoxin B1 in peanuts. To avoid the matrix effect, the aflatoxin B1 in the samples was extracted and concentrated by dispersive liquid-liquid microextraction. The mass spectrometer was operated in the positive ion mode to monitor the intact molecular ion (m/z 313, MH+ ) and product ion (m/z 241) of aflatoxin B1 using multiple reaction monitoring. RESULTS: Since no clean-up procedure of the sample was required, the sampling step and the subsequent mass spectrometric detection of the aflatoxin B1 was completed in less than 5 min. The limit of detection of aflatoxin B1 is at the sub-ppb level. The results obtained by DEP-MS/MS were also validated by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Recovery of aflatoxin B1 in the sample was evaluated by analyzing spiked aflatoxin B1 with LC/MS/MS to be 85% and DEP-MS/MS to be 84%. CONCLUSIONS: DEP-MS/MS combined with a simple dispersive liquid-liquid microextraction procedure was successfully used for the quantitative analysis of AFB1 in nut samples. Due to its high efficiency, it is promising in providing important toxicological information for food safety in the real world. Copyright © 2017 John Wiley & Sons, Ltd.

Formation of Metal-Adducted Analyte Ions by Flame-Induced Atmospheric Pressure Chemical Ionization Mass Spectrometry.

A flame-induced atmospheric pressure chemical ionization (FAPCI) source, consisting of a miniflame, nebulizer, and heated tube, was developed to ionize analytes. The ionization was performed by reacting analytes with a charged species generated in a flame. A stainless steel needle deposited with saturated alkali chloride solution was introduced into the mini oxyacetylene flame to generate alkali ions, which were reacted with analytes (M) generated in a heated nebulizer. The alkali-adducted 18-crown-6 ether ions, including (M + Li)(+), (M + Na)(+), (M + K)(+), (M + Rb)(+), and (M + Cs)(+), were successfully detected on the FAPCI mass spectra when the corresponding alkali chloride solutions were separately introduced to the flame. When an alkali chloride mixture was introduced, all alkali-adducted analyte ions were simultaneously detected. Their intensity order was as follows: (M + Cs)(+) > (M + Rb)(+) > (M + K)(+) > (M + Na)(+) > (M + Li)(+), and this trend agreed with the lattice energies of alkali chlorides. Besides alkali ions, other transition metal ions such as Ni(+), Cu(+), and Ag(+) were generated in a flame for analyte ionization. Other than metal ions, the reactive species generated in the fossil fuel flame could also be used to ionize analytes, which formed protonated analyte ions (M + H)(+) in positive ion mode and deprotonated analyte ions (M - H)(-) in negative ion mode.

Rapid detection of alteration of serum IgG in patients with schizophrenia after risperidone treatment by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry.

RATIONALE: The aim of the study was to use a technique that combines acid hydrolysis and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS) in order to detect the serum biomarkers of patients diagnosed with schizophrenia both before and after four-week antipsychotic treatment with risperidone. METHODS: During this study's two-year period, inpatients were diagnosed with schizophrenia using the Structured Clinical Interview for DSM-IV Axis I Disorders. Severity was then evaluated using the Positive and Negative Syndrome Scale both at baseline and at endpoint following four-week treatment with risperidone. The patients' serum biomarkers were quickly measured using acid hydrolysis and MALDI-TOF MS. The resulting peptides were then analyzed using MALDI-TOF MS. We constructed a receiver operating characteristic (ROC) curve for the evaluated biomarkers. RESULTS: We recruited 20 pairs of participants for this study. The experimental group was treated with serum protein with HCl for 10 minutes to effectively hydrolyze abundant proteins. The target peptide, the immunoglobulin gamma chain (IgG), was then rapidly detected using this manner. A significant difference was found in the IgG levels of patients with schizophrenia before and after antipsychotic treatment. We constructed a ROC curve based on the IgG, and the area under said curve was 0.969. In comparison to conventional detection protocols, this method takes only minutes to complete and is also less costly. CONCLUSIONS: This study found that applying acid hydrolysis with MALDI-TOF MS technology could rapidly differentiate serum IgG levels in patients with schizophrenia before and after being treated with risperidone. This IgG difference may enhance the understanding of mechanism of antipsychotic treatment of schizophrenia. Copyright © 2016 John Wiley & Sons, Ltd.

Flame-induced atmospheric pressure chemical ionization mass spectrometry.

RATIONALE: Charged species such as formylium (CHO(+) ), hydronium (H3 O(+) ), and water clusters [H3 O(+) (H2 O)n ] are commonly found in flames. These highly reactive species can react with analytes via ion-molecule reactions (IMRs) to form analyte ions. A new mass spectrometric technique, named flame-induced atmospheric pressure chemical ionization mass spectrometry (FAPCI-MS), was developed to characterize organic compounds via these mechanisms. METHODS: A commercial corona-discharge atmospheric pressure chemical ionization (APCI) source was modified by replacing the corona needle with a flame to make a FAPCI source. Liquid samples were vaporized in a heated tube and delivered to the IMRs region by nitrogen to react with the charged species generated by a flame. Analytes on surfaces were directly desorbed and ionized by a flame using the technique called desorption-FAPCI-MS (DFAPCI-MS). RESULTS: Intact molecular ions of various chemical and biological compounds were successfully characterized by FAPCI-MS. The FAPCI mass spectra are nearly identical to those obtained by traditional APCI-MS. The limit of detection (LOD) of reserpine by FAPCI-MS was 50 µg L(-1) with a linear calibration curve (R(2) = 0.9947) from 100 µg L(-1) to 10 mg L(-1) . The LOD for ketamine by DFAPCI-MS was estimated to be less than 0.1 ng. CONCLUSIONS: In FAPCI, analytes are not incinerated but vaporized and introduced into the ion source to react with the reactive charged species generated by a flame. The features of the FAPCI source include: configuration is very simple, operation is easy, high voltage or inert gas is unnecessary, and the source is maintenance free. Various combustible gases, solvents and solids are useful flame fuels for FAPCI. Copyright © 2016 John Wiley & Sons, Ltd.

Rapid point-of-care identification of oral medications in gastric lavage content by ambient mass spectrometry in the emergency room.

RATIONALE: Acute poisoning should be handled with high efficiency in order to minimize morbidity and mortality in the emergency room. Unfortunately, history-taking and physical examination are not always reliable. Mis-swallowing of oral medications is common in the pediatric group. This study aimed at developing a rapid point-of-care ambient mass spectrometric method for the early identification of ingested oral medications in gastric lavage content. METHODS: Four different types of oral medications that are most commonly mis-swallowed by children were diluted to different concentrations. Each of these chemical solutions was mixed with human gastric lavage content. A direct metallic sampling probe was dipped into the solution. It was then inserted promptly into the thermal desorption electrospray ionization source to carry out ionization and subsequent mass spectrometric analysis of the medications. The corresponding compounds were identified through matching of the obtained mass spectrometric data with those provided by well-established databases. RESULTS: Since no pretreatment of the specimen was required, the sampling step, and the subsequent thermal desorption electrospray ionization and mass spectrometric detection of the medications were completed within 30 s. Mass spectra were obtained for four different kinds of oral medication. The limit-of-detection of the four tested oral medications in gastric lavage content is at sub-ppm level, which is sensitive enough for emergency medicine applications since the quantities of medications ingested by pediatric patients are usually much higher. CONCLUSIONS: Thermal desorption electrospray ionization mass spectrometry, with informational support provided by an online mass spectral database, allows for early point-of-care identification of mis-swallowed oral medications in the evacuated gastric lavage contents obtained from gastric lavage of patients in the emergency room, and it is promising in providing important toxicological information to ensure the appropriateness of the subsequent medical management. Copyright © 2016 John Wiley & Sons, Ltd.

The upregulation of zinc finger protein 670 and prostaglandin D2 synthase in proliferative vitreoretinopathy.

PURPOSE: Proteins in the vitreous play an important role on the induction of proliferative vitreoretinopathy (PVR) after retinal detachment. The aim of this study was to investigate the variation of protein patterns in the vitreous of PVR eyes and examine whether differentially expressed protein levels were expressed in experimental PVR retina. METHODS: Vitreous samples from PVR and macular hole patients were selected for proteomic analysis. The vitreous protein samples were separated by two-dimensional electrophoresis (2-DE). The differentially expressed protein spots in the two groups were excised and subjected to in-gel digestion and identification by electrospray ionization mass spectrometry (ESI-MS) analysis. Two differentially expressed proteins, zinc finger protein 670 (ZFP 670) and prostaglandin D2 synthase (PGD2S), were further validated by immunohistochemical staining and western blotting analysis in the retina of the experimental rabbit PVR model. RESULTS: In proteome analysis of human vitreous samples, five proteins had increased expression in PVR, including zinc finger protein 670 (ZFP 670), prostaglandin D2 synthase (PGD2S), IgG (Immunoglobulin G) light chain, transthyretin precursor, and haptoglobin precursor. ZFP 670 and PGD2S levels were expressed significantly higher in the experimental PVR retinas than in the control group. CONCLUSIONS: Levels of ZFP 670 and PGD2S were elevated in the vitreous fluid of patients with PVR. In addition, there were higher expressions of ZFP 670 and PGD2S in the experimental PVR retina. This result will expand our knowledge of pathophysiologic characteristics of PVR, and might be helpful for further developing possible treatment on this disorder.