Search

We developed a simple, paper‐based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter‐balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes. One end of the paper strip was cut into a sharp point and positioned near the inlet of a MS. The stacked analyte bands move toward the paper tip with the EOF where they are ionized by paper spray. The device was applied to analysis of PFAS in tap water with sub part‐per‐trillion detection limits in less than ten minutes with no sample pretreatment. Analysis of opioids in urine also occurs in minutes. The crucial parameters to enable stacking, separation, and MS ionization of both positively and negatively charged analytes were determined and optimized. Experimental and computational modeling studies confirm the electrokinetic stacking and analyte transport mechanisms. On‐paper separations were carried out by stacking analyte bands at different locations depending on their electrophoretic mobility, achieving baseline separation in some cases. [ABSTRACT FROM AUTHOR]

We developed a simple, paper‐based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter‐balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes. One end of the paper strip was cut into a sharp point and positioned near the inlet of a MS. The stacked analyte bands move toward the paper tip with the EOF where they are ionized by paper spray. The device was applied to analysis of PFAS in tap water with sub part‐per‐trillion detection limits in less than ten minutes with no sample pretreatment. Analysis of opioids in urine also occurs in minutes. The crucial parameters to enable stacking, separation, and MS ionization of both positively and negatively charged analytes were determined and optimized. Experimental and computational modeling studies confirm the electrokinetic stacking and analyte transport mechanisms. On‐paper separations were carried out by stacking analyte bands at different locations depending on their electrophoretic mobility, achieving baseline separation in some cases. [ABSTRACT FROM AUTHOR]

Turmeric and ginger are extensively employed as functional ingredients due to their high content of curcuminoids and gingerols, considered the key bioactive compounds found in these roots. In this study, we present an innovative and fast method for the assay of curcuminoids and gingerols in different foods containing the two spices, with the aim of monitoring the quality of products from a nutraceutical perspective. The proposed approach is based on paper spray tandem mass spectrometry coupled with the use of a labeled internal standard, which has permitted to achieve the best results in terms of specificity and accuracy. All the calculated analytical parameters were satisfactory; accuracy values are around 100% for all spiked samples and the precision data result lower than 15%. The protocol was applied to several real samples, and to demonstrate its robustness and reliability, the results were compared to those arising from the common liquid chromatographic method. [ABSTRACT FROM AUTHOR]

Introduction: Distinguishing and categorizing the origin of garlic are highly significant, considering its widespread use as a flavoring agent. With billions of dollars annually in global trade, garlic is frequently susceptible to fraudulent practices. Methodology: Paper spray ionization mass spectrometry (PS‐MS) was employed to quickly analyze garlic samples from distinct geographic origins: China and Brazil. The so‐generated PS‐MS data were treated with metabolomic multivariate approaches, and the garlic samples from these different geographic regions were easily discriminated. Results: Brazilian garlic was characterized to contain higher levels of amino acids, such as arginine, proline, and valine, and organosulfur compounds, such as allicin, alliin, and l‐γ‐glutamil‐S‐allyl‐l‐cysteine, compared to Chinese garlic. The PS‐MS data were treated employing multivariate approaches, typically used in the metabolomics field, and this protocol was promptly able to discern among both types of samples. Conclusion: Hence, this combined strategy holds promise not only as an effective tool for the authentication of the geographical origin of garlic but also as a powerful means for biomarker discovery. [ABSTRACT FROM AUTHOR]

Multiple protocols have been reported to fabricate paper-based analytical devices (PADs). However, some of these techniques must be revised because of the instrumentation required. This paper describes a versatile and globally affordable method to fabricate PADs using office paper as a substrate and a laser printing technique to define hydrophobic barriers on paper surfaces. To demonstrate the feasibility of the alternatives proposed in this study, the fabrication of devices for three types of detection commonly associated with using PADs was demonstrated: colorimetric detection, electrochemical detection, and mass spectrometry associated with a paper-spray ionization (PSI-MS) technique. Besides that, an evaluation of the type of paper used and chemical modifications required on the substrate surface are also presented in this report. Overall, the developed protocol was suitable for using office paper as a substrate, and the laser printing technique as an efficient fabrication method when using this substrate is accessible at a resource-limited point-of-need. Target analytes were used as a proof of concept for these detection techniques. Colorimetric detection was carried out for acetaminophen, iron, nitrate, and nitrite with limits of detection of 0.04 μg, 4.5 mg mL−1, 2.7 μmol L−1, and 6.8 μmol L−1, respectively. A limit of detection of 0.048 fg mL−1 was obtained for the electrochemical analysis of prostate-specific antigen. Colorimetric and electrochemical devices revealed satisfactory performance when office paper with a grammage of 90 g m−2 was employed. Methyldopa analysis was also carried out using PSI-MS, which showed a good response in the same paper weight and behavior compared to chromatographic paper. [ABSTRACT FROM AUTHOR]

A paper spray tandem mass spectrometric (PS-MS/MS) method without column separation was developed for the rapid screening of clonidine in dietary supplements. PS-MS/MS provided acceptable performance compared to high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) in terms of limits of detection and quantification, accuracy, and precision. To overcome ionization suppression of complicated plant-based pharmaceutical products, nizatidine, tizanidine, and apraclonidine were investigated as internal standards. A more similar structured internal standard is most suitable for matrix effect compensation. The developed method has advantages of simplicity and speed for the screening of clonidine in dietary supplements. [ABSTRACT FROM AUTHOR]

The rise of fentanyl and fentanyl analogs in the drug supply pose serious threats to public health. Much of these compounds enter the United States through shipping routes. Here we provide a method for fentanyl screening and analysis that utilizes pressure‐sensitive adhesive (PSA) lined paper to recover drug residues from parcel‐related surfaces. The paper used is commercially available repositionable notes (also called post‐it or sticky notes). From this paper, mass spectra were obtained by paper spray‐mass spectrometry (PS‐MS), where PSA paper served as both a sampling and analysis substrate. Seven fentanyl‐related compounds were analyzed: fentanyl, 4‐anilino‐N‐phenethylpiperidine (4‐ANPP), N,1‐diphenethyl‐N‐phenylpiperidin‐4‐amine (phenethyl‐4‐ANPP), valerylfentanyl, 4‐fluoroisobutyrylfentanyl (4‐FIBF), carfentanil, and p‐fluorofentanyl. These compounds were recovered by PSA paper and identified by PS‐MS from packaging tape and plastic at 50 ng and from cardboard and shipping labels at 100 ng. The impact of cutting agents on PS‐MS analysis of fentanyl analogs was explored. No trends of analyte suppression were found at high concentrations of the cutting agents caffeine, diphenhydramine, and lidocaine when recovered from surfaces. A cartridge that required no precise cutting of PSA paper prior to sampling or analysis was evaluated for use in PS‐MS for fentanyl screening. Recovery and detection of fentanyl from plastic sheeting was demonstrated with this cut‐free cartridge. The cut‐free cartridge showed somewhat less consistency and lower analyte signal than the standard cartridge, but performance was suitable for potential screening applications. In combining PSA surface sampling with PS‐MS for drug screening, both sampling and detection of fentanyl‐related compounds is simple, rapid, and low‐cost. [ABSTRACT FROM AUTHOR]

Rationale: The burgeoning concern of N‐nitrosamine (NAM) contamination found in various pharmaceutical compositions has increased the demand for rapid and reliable screening methods to better assess the breadth of the problem. These carcinogenic compounds are also found in food, water, and soil, and they have been used in poison‐related homicides. Methods: A combination of complementary, ambient ionization methods, paper spray ionization (PSI) and filter cone spray ionization (FCSI)‐mass spectrometry (MS), was characterized towards trace‐level residue screening of select NAMs (e.g., N‐nitrosodimethylamine, N‐nitrosodiethylamine, N‐nitrosodibutylamine) directly from complex and problematic matrices of interest, including prescription and over‐the‐counter tablets, drinking water, soil, and consumable goods. Spectral data for analyte confirmation and detection limit studies were collected using a Thermo LCQ Fleet ion trap mass spectrometer. Results: PSI‐MS and FCSI‐MS readily produced mass spectral data marked by their simplicity (e.g., predominantly protonated molecular ions observed) and congruence with traditional electrospray ionization mass spectra in under 2 min. per sample. Both methods proved robust to the complex matrices tested, yielding ion signatures for target NAMs, as well as active pharmaceutical ingredients for analyzed tablets, flavorants inherent to food products, etc. Low part‐per‐million detection limits were observed but were shown dependent on sample composition. Conclusions: PSI‐MS and FCSI‐MS were successful in detecting trace‐level NAMS in complex liquid‐ and solid‐phase matrices with little to no prior preparation. This work suggests that these methodologies can provide a means for assessing problematic pharmaceutical adulterants/degradants for expedited quality control, as well as enhancing environmental stewardship efforts and forensic investigations. [ABSTRACT FROM AUTHOR]

Illicit drug trafficking and abuse is a significant public safety and health concern. Color tests are commonly used for drug screening, but their poor specificity results in false positives. This study demonstrates the combination of drug residue collection using pressure-sensitive adhesive paper, on-paper color testing, and post-reaction analysis by paper spray mass spectrometry (PS-MS) on both portable and benchtop ion trap MS. All steps, including residue collection, color testing, and paper spray analysis, were performed on the same piece of paper. Three common color tests were investigated: the cobalt thiocyanate test for cocaine, the Simon test for methamphetamine, and the Marquis test for phenethylamine stimulants and opiates. The detection threshold for color tests ranged from 1.25 to 10 μg on paper. Drug residues were successfully confirmed by paper spray MS at the color test threshold in all cases, except for heroin after reaction with the Marquis reagent, when using the portable MS. In this case, the MS detection threshold was 4-fold higher than the color test threshold. The stability of the color test products was assessed through a time study. Drug residues could be detected by MS at least 24 hours after reaction. A series of realistic samples, including false positives, were analyzed to demonstrate the technique's utility in real-world scenarios. Overall, combining color tests with PS-MS offers a rapid, low-cost method for the collection and analysis of illicit drugs. [ABSTRACT FROM AUTHOR]

Hypericum perforatum L. (St. John's wort) is one of the world's most consumed medicinal plants for treating depression and psychiatric disorders. Counterfeiting can occur in the medicinal plant trade, either due to the lack of active ingredients or the addition of substances not mentioned on the labels, often without therapeutic value or even harmful to health. Hence, 43 samples of St. John's wort commercially acquired in different Brazilian regions and other countries were analyzed by paper spray ionization mass spectrometry (PS‐MS) and modeled by principal component analysis. Hence, samples (plants, capsules, and tablets) were extracted with ethanol in a solid–liquid extraction. For the first time, PS‐MS analysis allowed the detection of counterfeit H. perforatum samples containing active principles typical of other plants, such as Ageratum conyzoides and Senna spectabilis. About 52.3% of the samples were considered adulterated for having at least one of these two species in their composition. Furthermore, out of 35 samples produced in Brazil, only 13 were deemed authentic, having only H. perforatum. Therefore, there is a clear need to improve these drugs' quality control in Brazil. [ABSTRACT FROM AUTHOR]

Accurate quantification of blood creatinine is important to estimate the glomerular filtration rate. Existing techniques using liquid chromatography tandem mass spectrometry (LC–MS/MS) have a high accuracy and eliminate most interferences encountered in routine enzymatic and Jaffé methods. However, they require laborious and time-consuming sample treatment and data acquisition. The aim of this study is to develop a fast and simple method to enable a direct analysis of whole blood creatinine with performance measures that are comparable to conventional LC–MS/MS. 5μL whole blood is formed as a three-dimensional spheroid on hydrophobic silanized paper substrates which then undergoes paper-spray ionization—tandem mass spectrometry (PSI–MS/MS). The method is validated using real human samples and compared with LC–MS/MS. PSI–MS/MS whole blood analysis exhibited a lower limit of quantification of 2.5 μg/mL, precision ≤ 6.3%, recovery in the range of 88–94% and excellent linearity (R2 > 0.99; 2.5—20 μg/mL) covering the normal range for creatinine levels. Creatinine levels were comparable to those measured by LC–MS/MS with small deviations of less than 0.3 μg/mL. This simple, fast and accurate microsampling technique for direct analysis of creatinine from whole blood shows promise for routine clinical screening and monitoring. This approach can be readily extended for other analytes of interest and, due to inherent advantages relating to cost, storability, speed, and simplicity, it can be especially advantageous for use in resource-limited settings. [ABSTRACT FROM AUTHOR]

A direct mass spectrometry method utilizing reactive paper spray ionization was developed for sensitive cannabinoid quantitation in biofluid matrices. The ca. 2-minute sample measurements used on-paper derivatization to significantly increase paper spray mass spectrometry (PS-MS) positive ion mode sensitivity while minimizing sample preparation steps. Calibrations demonstrate high linearity, with R2 > 0.99 for (−)-trans-Δ9-tetrahydrocannabinol (THC) in oral fluid and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in urine. The limit of detection and lower limit of quantitation were 0.78 and 10 ng mL−1 for THC in oral fluid and 1.3 and 10 ng mL−1 for THC-COOH in urine, respectively. THC-COOH levels measured by reactive PS-MS in seven spiked human urine samples showed bias of −9.4 to 5.9%, and percent difference values of −16.8 to 9.8% in comparison with a reference LC-MS method. Based upon the method simplicity, validation experiments, sensitivity, and rapidity, we conclude that reactive PS-MS has potential applications for rapid cannabinoid drug testing in urine and oral fluid. [ABSTRACT FROM AUTHOR]

Tobacco smoke contains a large number of harmful substances and has been widely proved to be able to induce a variety of human diseases. Human eyes are exposed to ambient air for a long time in daily life and are susceptible to air pollutants such as tobacco smoke in the air. Therefore, direct monitoring of characteristic components of tobacco smoke in human tears is expected to efficiently assess the exposure level of tobacco smoke to human eyes. Due to human tears at the microliter level, conventional sample collection and chemical analysis methods are a challenging task. Mass spectrometry (MS) has the unique advantages of high sensitivity, specificity and speed, especially, the development of ambient MS with solid substrates has greatly facilitated direct sample analysis with little or no sample pretreatment. Schirmer paper strip is clinically used for sampling of human tears, which is safe, non-invasive, and can be used for measuring the volume of tears. In this study, a small Schirmer paper strip was further prepared for noninvasive microsampling of human tears which exposed to tobacco smoke, and high voltage and an organic solvent were applied onto Schirmer paper to directly generate paper spray ionization for ambient MS analysis. The good analytical performances, including sensitivity (LOD: 0.1 μg/L, S/N≥3; LOQ: 1.0 μg/L, S/N≥10), precision (RSD: 4.89%-7.61%, n=5, with internal standard), recovery (98%-102.1%, n=5), and linear range (0.5-50 μg/L, R2=0.991 8) were achieved. Monitoring nicotine in human tears under different exposure times was also investigated, showing that the concentration of nicotine will the increase with increasing the exposure time ranging from 0 to 8 min. The nicotine can research to be 45 μg/L after burning a cigarette (about 8 min). The retention time of nicotine in human tears was found to be about 20 min (less than 5%), and the half-life time is about 4 min. Overall, our results show that Schirmer paper spray mass spectrometry could be used for qualitative and quantitative detection of trace environmental exposures such as nicotine in human eyes with many advantages, including safe, noninvasive, easy-to-operation, low-consumption as low as 1.0 μL, and thus has potential for many applications in environmental exposure and human health. [ABSTRACT FROM AUTHOR]

Phospholipids (PLs) are major constituents of cell membranes, play important roles in cell proliferation and death, as well as in signal transduction, and therefore are relevant biomarkers for different pathologies. On the other hand, when the analysis of small compounds, such as therapeutics in blood is desired, then phospholipids are part of the matrix and cause serious interference during analysis. Currently, both the analysis and removal of PLs from biological samples are limited by extensive sample preparation and instrumental separation. A fast and simple quantitative Ti4+-modified paper spray tandem mass spectrometric (TiPS-MS/MS) method was established in urine, where the enrichment of phospholipids was achieved, as well as reduction of matrix effects (primarily caused by high salt content) that ultimately led to improved sensitivity and selectivity. The method could achieve a physiologically relevant limit of detection (0.01–0.03 μg mL−1). Also, the usefulness of the Ti4+-modified paper was investigated in the opposite mode, namely for the selective removal of phospholipids from matrices such as plasma. Clonidine is used as model compound, as the detection of this compound is known to suffer from ion suppression by phospholipids. Compared with blank paper spray tandem mass spectrometry, the limit of detection could be improved from 0.3 μg mL−1 to 0.03 μg mL−1 by employing a Ti4+-modified paper on top of the spray tip to capture phospholipids from the sample. A novel Ti4+-modified paper was developed to allow for rapid solid-phase extraction of phospholipids from urine or selective removal from plasma, followed by direct paper spray mass spectrometric detection as a fast and convenient sample preparation and analysis combination. The paper properties are based on the Ti4+ metal ion, which can selectively bind phosphate-containing compounds under acidic conditions, and its applicability was demonstrated in relevant biological matrices. • Ti4+-modified paper spray tips for selective phospholipids enrichment/removal. • Ti4+ modified paper spray mass spectrometry (TiPS-MS/MS) was developed for analysis of phospholipids. • Fast extraction/analysis of phospholipids in urine demonstrated at physiological levels. • TiPS-MS/MS was developed for reducing matrix effects in plasma. [ABSTRACT FROM AUTHOR]

Rationale: The effort to make fake documents look real leads to the use of crickets and beverages to produce artificially aged papers, as land titles, based on yellowing caused by the use of these methods. An old practice in Brazil, called "cricketing", has led to the misappropriation of Brazilian land using these documents. We propose a rapid, simple, instantaneous and non‐destructive method to identify artificially aged papers by easy ambient sonic‐spray ionization mass spectrometry (EASI‐MS) analysis. Methods: Three typical aging procedures were used to obtain artificially aged papers using coffee, cola drink, and crickets, with the papers being analyzed by EASI‐MS. Multivariate statistical analyses were performed on the data to find the sample groups and to study the most relevant ions of each ageing procedure. High‐resolution MS (HRMS) was used to obtain the exact masses and attribute formulae to relevant ions present in the samples. Results: The combination of EASI‐MS and multivariate statistical analyses allowed us to identify the most relevant ions to classify the adulteration of documents and HRMS identified most of these relevant ions. TMS fingerprinting in combination with multivariate analysis also demonstrated that this approach can qualitatively differentiate all the examined paper samples. Conclusions: We developed a cheap, fast and easy method that can help to elucidate counterfeit documents that have been artificially aged, helping to identify chemical additives and one that can be used in forensic laboratories. [ABSTRACT FROM AUTHOR]

A new method for a fast molecular profiling of olive oil unsaponifiable fraction has been developed. This approach, based on paper spray mass spectrometry, allows obtaining MS data with only a few minutes of analysis and without significant solvent and disposable consumption. Tandem mass spectrometry and high-resolution mass spectrometry experiments have been performed to identify the main ions detected. The MS data coming from the analyses of sixty-three samples of three different olive oil categories: extra virgin olive oil (EVOO), virgin olive oil (VOO), and pomace olive oil (POO), have been used to test the discriminative potential. Both unsupervised (PCA and HCA) and supervised (kNN and LDA) chemometric procedures have been applied with good results in prediction. The same approach was tested using direct infusion mass spectrometry data to confirm the ability of paper spray fingerprinting to classify different olive oils correctly. [Display omitted] • Olive oil profiling of unsaponifiable fraction by paper spray mass spectrometry. • The method was applied to sixty-three real samples. • The most relevant species have been characterized by MS/MS and HRMS analyses. • Chemometric approaches tested to evaluate the discriminative capability of PS-MS. • The developed methodology can be used for quality control purposes. [ABSTRACT FROM AUTHOR]

Carbon fiber paper (CFP) is commonly used as a proton exchange membrane in fuel cells due to its prominent areal electrosorption capacity, exceptional conductivity and excellent chemical stability. In this paper, we first explored the feasibility of carbon fiber paper as a specific paper substrate in paper spray ionization mass spectrometry (PSI-MS). The results demonstrated that CFPSI-MS combines the merits of PSI and carbon fiber ionization (CFI) and exhibits better performance of various compound analyses than either of these techniques alone. The application of CFP can highly enhance the signal stability and detection sensitivity of a diverse array of analytes, especially in negative ionization mode. The ion intensity of target analytes such as saccharides and flavonoids was improved 2-90-fold. Many nonpolar/low-polarity analytes, such as polycyclic aromatic hydrocarbons, which are difficult to ionize by traditional PSI-MS, were successfully detected by CFPSI-MS with a 2.5 kV high voltage. Moreover, CFPSI-MS presents high sensitivity in semiquantitative analysis, and the limits of detection (LODs) of cyclic adenosine monophosphate (CAMP), naringin and tivantinib in whole blood were improved 2-100-fold compared to those in traditional PSI-MS. In real sample analysis, CFPSI-MS also exhibits excellent capability in human breath analysis and blood metabolomic profiling. [Display omitted] • Carbon fiber paper with high conductivity and good ionization capability was first used in paper spray ionization mass spectrometry. • Carbon fiber paper is easily obtainable and reusable, and no extra chemical modification is needed. • CFPSI-MS showed excellent detection sensitivity in analyzing non/low-polar analytes and polar molecules, especially in negative ionization mode. • Improved performance of real sample analysis and semiquantitative analysis was demonstrated by CFPSI-MS. [ABSTRACT FROM AUTHOR]

Mitigation of the peroxide explosive threat, specifically triacetone triperoxide (TATP) and hexamethylene triperoxide diamine (HMTD), is a priority among the law enforcement community, as scientists and canine (K9) units are constantly working to improve detection. We propose the use of paper spray ionization–high-resolution mass spectrometry (PSI-HRMS) for detection of peroxide explosives in biological matrices. Occurrence of peroxide explosives and/or their metabolites in biological samples, obtained from urine or blood tests, give scientific evidence of peroxide explosives exposure. PSI-HRMS promote analysis of samples in situ by eliminating laborious sample preparation steps. However, it increases matrix background issues, which were overcome by the formation of multiple alkali metal adducts with the peroxide explosives. Multiple ion formation increases confidence when identifying these peroxide explosives in direct sample analysis. Our previous work examined aspects of TATP metabolism. Herein, we investigate the excretion of a TATP glucuronide conjugate in the urine of bomb-sniffing dogs and demonstrate its detection using PSI from the in vivo sample. [ABSTRACT FROM AUTHOR]

This work describes a novel methodology to analyze four tricyclic antidepressants (amitriptyline, doxepin, imipramine and, nortriptyline) in urine samples by combining supramolecular microextraction and paper spray ionization mass spectrometry (PS-MS). The proposed method uses a supramolecular solvent in which reverse micelles of 1-decanol are dispersed in tetrahydrofuran (THF)/water. The extraction of the tricyclic antidepressants at pH 9.0 requires a sample volume of 10.0 mL, short extraction time (1.0 min of extraction and 5 min of centrifugation), low amounts of organic solvent (50 μL of 1-decanol and 200 μL of THF), and provides high preconcentration factors: 96.9 to amitriptyline, 93.6 to doxepin, 71.3 to imipramine, and 146.9 to nortriptyline. The quantification by PS-MS is fast and straightforward because chromatographic separation is not required and all analytes were determined simultaneously. The limits of detection (LOD), quantification (LOQ), and the precision (RSD, %) of the developed method ranged between 5.2 and 8.6 μg L−1, 17.4–28.7 μg L−1 and 1.3–12.9%, respectively. Urine samples of five individuals (three males and two females) were used for accuracy evaluation. The accuracy obtained in these spiked urine samples at μg L−1 levels varied from 95.3 to 112.0%. The method also provided clean mass spectra with a high signal-to-noise ratio, which demonstrates the analytical appeal combination of supramolecular microextraction with determination by paper spray mass spectrometry. Image 1 • Supramolecular microextraction provided gain in sensitivity and sample's clean-up. • The method presented high preconcentration factors for TCAs in urine. • PS-MS was used to TCA's quantification by internal standard calibration. • PS-MS analyses were fast and without interference from the sample matrix. • The method employed minimal sample and solvents volumes. [ABSTRACT FROM AUTHOR]

Rationale: Paper spray offers a rapid screening test without the need for sample preparation. The incomplete extraction of paper spray allows for further testing using more robust, selective and sensitive techniques such as liquid chromatography/mass spectrometry (LC/MS). Here we develop a two‐step process of paper spray followed by LC/MS to (1) rapidly screen a large number of samples and (2) confirm any disputed results. This demonstrates the applicability for testing medication adherence from a fingerprint. Methods: Following paper spray analysis, drugs of abuse samples were analysed using LC/MS. All analyses were completed using a Q Exactive™ Plus Orbitrap™ mass spectrometer. This two‐step procedure was applied to fingerprints collected from patients on a maintained dose of the antipsychotic drug quetiapine. Results: The extraction efficiency of paper spray for two drugs of abuse and metabolites was found to be between 15 and 35% (analyte dependent). For short acquisition times, the extraction efficiency was found to vary between replicates by less than 30%, enabling subsequent analysis by LC/MS. This two‐step process was then applied to fingerprints collected from two patients taking the antipsychotic drug quetiapine, which demonstrates how a negative screening result from paper spray can be resolved using LC/MS. Conclusions: We have shown for the first time the sequential analysis of the same sample using paper spray and LC/MS, as well as the detection of an antipsychotic drug from a fingerprint. We propose that this workflow may also be applied to any type of sample compatible with paper spray, and will be especially convenient where only one sample is available for analysis. [ABSTRACT FROM AUTHOR]

We developed a highly efficient and low‐cost organic solvents‐resistant microfluidic paper‐based analytical device (μPAD) coupled with paper spray mass spectrometry (PS‐MS) for quantitative determination of C18‐ceramide as a prognostic biomarker for several diseases. Several models of μPAD patterns have been examined to select the most resistant and efficient microchannel barriers, which can provide continuous spray at ionization zone and prevent "coffee ring" effect. Moreover, the developed μPAD has enabled the analysis of low concentration of C18‐ceramide because of the maximum supply of deposited analyte through microchannel. The MS results confirmed the formation of doubly and singly charged metal ion complexes between ceramide and different metal ions. Notably, the complexation that occurs between lithium ions and C18‐ceramide showed a high relative abundance compared with other formed complexes. Taking into account the relative abundance of complex [Cer + Li]+ at 572.8 m/z, it can be considered as a stable ion and therefore be used for the analysis of C18‐ceramide at low concentrations. Complexation of C18‐ceramide and lithium confirmed with quantum chemical calculations. The proposed method represents good linearity with a regression coefficient of 0.9956 for the analysis of C18‐ceramide and reaches a limit of detection to 0.84 nM. It has been adapted successfully for practical application in human serum samples with high recovery values in range of 92%–105%. The developed μPAD‐MS technique provides clear advantages by reducing the experimental steps and simplifying the operation process and enables to identify subnanomolar concentration of C18‐ceramide in human serum samples. [ABSTRACT FROM AUTHOR]

Propofol is a widely used intravenous anesthetic agent in sedation and general anesthesia. To improve the safety and maintain the depth of anesthesia, it is important to develop a rapid, sensitive, and reliable method to monitor the concentration of propofol in blood during anesthesia continuously. Here, we present a novel strategy based on paper spray ionization-mass spectrometry (PSI-MS) to detect propofol. Samples (in 10 μL) were mixed with methanol as protein precipitation solvent and 2,6-dimethylphenol as internal standard. Protein micro-precipitation was achieved with methanol by vortexing and centrifuging for 5 s each, and propofol was extracted to the supernatant. PSI-MS was performed in negative ionization mode, and MS signal lasted for 1 min. The analysis of a single sample was completed within 2 min. The area ratios of propofol to internal standard were calculated for quantification. Limit of detection of 5.5 ng mL−1 and limit of quantification of 18.2 ng mL−1 were achieved for propofol in whole blood. Calibration curve was linear in the range of 0.02–10 μg mL−1. The developed method was used successfully in monitoring the propofol concentration in 3 patients' whole blood during anesthesia, showing its further application in controlling and feeding-back target concentration infusion. [ABSTRACT FROM AUTHOR]

A fast methodology for the assay of parabens in drug and cosmetic preparations has been presented. The procedure developed is based on paper spray tandem mass spectrometry and isotope dilution approach. For each investigated paraben, the corresponding labeled standard has been used in order to improve the accuracy and reproducibility of the analyses. The MS experiments have been performed under MRM conditions, monitoring the transitions [M‐H]− → m/z 92 and [M‐H]− → m/z 98, respectively, for each analyte and the corresponding labeled internal standard. The quantitative assay has been performed using a calibration curve built from 2 to 15 mg/L. The method accuracy, in all case near 100%, was evaluated using fortified samples at two concentration levels, which are representative of the lower and the higher portion of calibration curve. The good values of LOQ, LOD, and reproducibility confirm the consistency of the developed approach. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal disease is a life-threatening condition that can be challenging to treat due to pathogen resistance, drug toxicity, and therapeutic failure secondary to suboptimal drug concentrations. Frequent therapeutic drug monitoring (TDM) is required for some anti-fungal agents to overcome these issues. Unfortunately, TDM at the institutional level is difficult, and samples are often sent to a commercial reference laboratory for analysis. To address this gap, the first paper spray-mass spectrometry assay for the simultaneous quantitation of five triazoles was developed. Methods: Calibration curves for fluconazole, posaconazole, itraconazole, hydroxyitraconazole, and voriconazole were created utilizing plasma-based calibrants and four stable isotopic internal standards. No sample preparation was needed. Plasma samples were spotted on a paper substrate in pre-manufactured plastic cartridges, and the dried plasma spots were analyzed directly utilizing paper spray-mass spectrometry (paper spray MS/MS). All experiments were performed on a Thermo Scientific TSQ Vantage triple quadrupole mass spectrometer. Results: The calibration curves for the five anti-fungal agents showed good linearity (R2 = 0.98–1.00). The measured assay ranges (lower limit of quantification [LLOQ]–upper limit of quantitation [ULOQ]) for fluconazole, posaconazole, itraconazole, hydroxyitraconazole, and voriconazole were 0.5–50 μg/mL, 0.1–10 μg/mL, 0.1–10 μg/mL, 0.1–10 μg/mL, and 0.1–10 μg/mL, respectively. The inter- and intra-day accuracy and precision were less than 25% over the respective ranges. Conclusions: We developed the first rapid paper spray-MS/MS assay for simultaneous quantitation of five triazole anti-fungal agents in plasma. The method may be a powerful tool for near-point-of-care TDM aimed at improving patient care by reducing the turnaround time and for use in clinical research. [ABSTRACT FROM AUTHOR]

Abstract Rapidly detecting trace levels of organic contaminants in complex mediums is a great challenge for mass spectrometry analysis. Especially in dealing with large quantities of soil samples, the laborious sample pretreatment process is exhausting and time consuming. Here, a simple method for quickly identifying and quantifying tetrabromobisphenol A (TBBPA) in soils and sediments has been developed via paper spray ambient mass spectrometry coupled with a stable isotope internal standard technique in this study. The soil and sediment extracts, spiked with a certain amount of 13C 12 -TBBPA (Ring-13C 12), are directly loaded and separated on chromatographic paper, sprayed and ionized by a high negative voltage, and ultimately analyzed by mass spectrometry without purification and chromatography separation processes. Data acquisition for each test can be finished within 1 min. In the quantification of TBBPA, a linear range of 0.1–100 µg L–1, a limit of detection of 0.039 µg L–1 and a relative standard deviation (c = 1.0 µg L–1, n = 5) of 5.3% are obtained. The spiking recoveries range from 90.4% to 101.1% for analyzing ten soil and sediment samples (0.012–30.14 µg g–1 dw), suggesting that the method should be a promising strategy for rapidly detecting organic pollutants in soils and sediments. Graphical abstract A simple method for quickly identifying and quantifying tetrabromobisphenol A (TBBPA) in soils and sediments has been developed via paper spray ambient mass spectrometry coupled with a stable isotope internal standard technique. fx1 Highlights • Tetrabromobisphenol A in soils and sediments can be rapidly and precisely detected. • Purification and chromatography separation processes are not needed. • As low as 0.039 µg L–1 of TBBPA (limit of detection) can be detected. • High-throughput analysis of soil and sediment samples is achieved. [ABSTRACT FROM AUTHOR]

A novel platform of microfluidic paper-based analytical devices (μPADs) for dual detection of bisphenol A (BPA), a model analyte, was fabricated using an electronic digital plotter to create the stacked layer of μPADs and generate the lateral-flow channel without using an external pump. Two detection techniques, including electrochemical detection and laser desorption ionization mass spectrometric detection (LDI-MS), were used complementarily to improve the precision in the detection of BPA. The fluid sample was delivered to both detection zones by the capillary action, automatically generated from the fabricated microfluidic device. For an electrochemical sensor, two ballpoint pens filled with silver nanoparticles (AgNPs) and multiwall carbon nanotube (MWCNT) ink were used to print onto the paper with a contact printing method using a digital plotter. To further improve the sensitivity, zinc oxide (ZnO) was used to modify both electrochemical and LDI-MS detection zones. For BPA detection, high electrocatalytic properties and strong UV absorption of ZnO promote the electron transfer in the electrochemical sensor and ionization efficiency in LDI-MS with low interferences compared with a conventional organic matrix. Under optimal conditions, this platform showed a dual detection capability for BPA with a detection limit of 0.35 μM for electrochemical detection and with an ultralow detection limit of 0.01 pM for LDI-MS. This novel platform might be very useful for trace analyses requiring high precision detection of various analytes. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • First application of PSI-MS on photodegraded and degraded spilled oil samples. • PSI-MS is shown to be a suitable technique for spilled oil analysis. • Parameter derived from PSI-MS spectra to estimate the degree of degradation of oils. Abstract Paper spray ionization mass spectrometry (PSI-MS) was applied for the first time to study temporal change of photo-oxidized and weathered oils subjected to degradation. PSI is chosen in this study because it is an optimal ionization technique for the analysis of degraded oils with limited sample quantity and prone to salt and particulate contamination. With PSI-MS, quantitative analysis of oils can be successfully performed with as little as 2 μg of oil sample. In addition, oil solutions containing up to 0.05% sodium chloride were successfully analyzed with PSI-MS. In the PSI-MS spectra of photo-degraded oils, the relative abundance of compounds having double equivalence value (DBE) ≥ 5 increased but those with DBE < 5 decreased in number. The summed abundance ratio of compounds having DBE < 5 and DBE ≥ 5 showed a negative exponential correlation with the duration of UV exposure in laboratory experiments. The same trend was observed from spilled oils obtained from the environment. Therefore, this ratio serves as an effective means to estimate the degree of weathering in spilled oils. [ABSTRACT FROM AUTHOR]

Rationale: Smoking is responsible for one in five deaths around the world. Thus, governments have been trying to reduce the number of active smokers by increasing taxes on products. This scenario creates a new problem by raising the consumption of illegally traded cigarettes, which are often seized and analyzed by police forces. Methods: Legal and illegal cigarette samples were extracted and analyzed using paper spray ionization mass spectrometry (PS-MS). The mass spectrometer was set to operate in full-scan positive ion mode to yield representative chemical profiles of each sample. The results were used to build a chemometric model using partial least squares discriminant analysis (PLS-DA) to discriminate between both sets of samples, i.e. legal and illegal. Results: The PS-MS procedure was fast, simple and efficient, yielding high-quality and reproducible mass spectra with a very good signal-to-noise ratio. Even though all samples displayed visually indistinguishable mass spectra, the PS-MS data handled by the PLS-DA approach furnished a model that reached sample classification with rates of 100% and 80% for the training and validation sets, respectively. Conclusions: A novel methodology was successfully developed associating the PSMS technique with chemometric analysis to differentiate between legal and illegal cigarettes. The PS-MS technique proved to be adequate for obtaining fingerprints of such types of samples despite high complexity, and a PLS-DA model was successfully constructed achieving 82.1% accuracy. [ABSTRACT FROM AUTHOR]

Rationale: The ability to detect and quantify the presence of specific inorganic elements and complexes is essential for environmental monitoring and nuclear safeguards applications. In this work, paper spray ionization mass spectrometry was used for the rapid chemical and isotopic characterization of trace inorganic species collected on cotton swipe substrates. The direct analysis of cotton swipes using this ambient ionization technique led to fast sample analysis that retained original chemical information of the source material with minimal sample preparation. Methods: Mass spectra were collected with an atmospheric pressure ionization, high‐resolution mass spectrometer for solutions containing uranyl acetate, uranyl chloride, uranyl nitrate, and uranyl tri‐n‐butylphosphate complexes. Gadolinium nitrate was used as an internal standard for the quantitative analysis of uranium. To demonstrate the ability to characterize inorganic contaminants in the presence of uranium, a multi‐element inorganic standard containing U, Bi, Pb, Cd, Fe, and Zn was deposited onto cotton substrates and directly analyzed without purification. Results: All elements doped on the cotton substrate were detected with strong signal‐to‐noise ratios (ca 1000 for UO2+ on multi‐element doped swipes) and high integrated intensities (>105 counts) from collection periods of approximately 1 min. Limits of detection were determined to be approximately 94 ng for UO2+ and uranyl acetate through the measurement of ppb level solutions. Conclusions: The rapid analysis of uranium and other inorganic‐containing samples while still retaining original chemical information (e.g. uranyl complexation) was demonstrated. Qualitative detection and speciation were achieved in less than 1 min of analysis. For uranium isotopic quantitation, longer accumulations (>15 min) can be sustained to improve the accuracy of minor 235U isotopic abundance measurements to approximately 1% error. [ABSTRACT FROM AUTHOR]

Electrospray ionization mass spectrometry (ESI-MS) analysis in the negative ion mode is adversely affected by ionization suppression caused by electrical discharge and the presence of salts. Paper spray mass spectrometry (PS-MS) also suffers from the above phenomenon, being built on principles similar to those of ESI. Herein, we report the use of a paper substrate modified by 1-[3-(trimethoxysilyl)propyl]urea to improve the sensitivity of quantitative PS-MS analysis in the negative ion mode. The obtained results demonstrated that the urea modified paper substrate can effectively bind anions and highly polar compounds in the sample solution, decreasing competitive ionization in the negative ion mode of PS-MS and significantly reducing the signal intensity of Cl − adducts. In addition, the analyte responses were also significantly improved owing to the decreased electrical discharge observed for the less polar surface to decrease electrical discharge. Compared to non-modified PS-MS, urea-modified PS-MS exhibits a much higher sensitivity, showing 2−109 times improved signal-to-noise ratio (S/N). In real sample analysis, the limits of detection (LODs) of salicylic acid in urine and terpene lactones in Ginkgo biloba extract (EGb) were improved 10-fold and 2–40-fold, respectively, compared to that of non-modified PS-MS. [ABSTRACT FROM AUTHOR]

A paper spray mass spectrometry (PS-MS) method for rapid and reliable analysis of benzalkonium chloride (BAC) in compound eye drops and body surface disinfectant was developed. The sample was dropped onto triangular filter paper, and high voltage (3.5 kV) was applied to form an electrospray. This method can provide the composition of benzalkonium chloride in samples without pretreatment, solvent or chromatographic separation, and the analysis time is only 10 s. The primary homologues C 12 -BAC, C 14 -BAC and C 16 -BAC of benzalkonium chloride were quantitatively analyzed using PS-MS. Samples were subjected to simple dilution and quantified using the internal standard method. Ion trap mass spectrometry was scanned using SIM mode. The linear ranges of C 12 -BAC, C 14 -BAC and C 16 -BAC were 1–100 μg mL −1 ; the linear regression coefficients were 0.998–0.999; the detection limits (LODs) were 0.1 μg mL −1 ; the limit of quantifications (LOQs) was <1 μg mL −1 , and the method validation indicated that the method precision and accuracy were good. Compared with HPLC-UV methods, there was no significant difference in the quantitative determination of the actual samples, but the analysis time for PS-MS is shorter (2 min). In addition, reagent consumption in PS-MS is small, and no chromatographic separation is needed, suggesting that PS-MS is especially suitable for high-throughput analysis. [ABSTRACT FROM AUTHOR]

Paper spray-mass spectrometry (PS-MS) is a rapid, solvent-efficient, and high-throughput analytical method for analyzing complex samples. In this study, a PS-MS method was developed to obtain MS profiles of Aurantii Fructus Immaturus ( aka Zhishi in Chinese) in positive and negative ion modes. In combination with multivariate analyses, including principal component analysis and cluster analysis, the PS-MS profiles of 25 batches of Zhishi were discriminated in 25 batches of Citri Reticulatae Pericarpium Viride ( aka Qingpi in Chinese; an adulterant of Zhishi). Moreover, a rapid quantitative analysis of synephrine, a prescriptive quality control component of Zhishi listed in the Chinese Pharmacopoeia, was conducted with PS-MS using synephrine-d2 as an internal standard (IS). The linearity range was 1.68–16.8 μg/mL (R 2 = 0.9985), the limit of quantitation was 0.5 μg/mL. Relative standard deviations in the intra- and inter-day precision of the MS were 4.87 and 4.90%, respectively. Compared with HPLC results, there was no significant difference in the quantitation of synephrine. This study demonstrated that the PS-MS method is useful for the rapid discrimination and quality control of Zhishi samples. [ABSTRACT FROM AUTHOR]

Here we introduce a new ambient ionization technique named laser assisted paper spray ionization mass spectrometry (LAPSI MS). In it, a 532 ± 10 nm, ≤10 mW laser pointer was shone on a triangularly cut paper along with high voltage, to effect ionization. The analyte solution was continuously pushed through a fused silica capillary, using a syringe pump, at a preferred infusion rate. LAPSI MS promises enhanced ionization with high signal intensity of polycyclic aromatic hydrocarbons (PAHs), which are normally not ionizable with similar ionization methods involving solvent sprays. LAPSI MS works both in positive and negative modes of ionization. A clear enhancement of signal intensity was visualized in the total ion chronogram for most analytes in the presence of the laser. We speculate that the mechanism of ionization is field assisted photoionization. The field-induced distortion of the potential well can be large in paper spray as the fibers comprising the paper are separated at tens of nanometers apart, and consequently, the analyte molecules are subjected to very large electric fields of the order of 107 Vcm-1. Ionization occurs from their distorted electronic states of reduced ionization energy, using the laser. Negative ion detection is also demonstrated, occurring due to the capture of produced photoelectrons. LAPSI MS can be used for monitoring in situ photoassisted reactions like the decarboxylation of mercaptobenzoic acid in the presence of gold and silver nanoparticles and the dehydrogenation reaction of 2,3-dihydro-1H-isoindole, which were chosen as examples. As an application, we have shown that paraffin oil, which is usually nonionizable by paper spray or by electrospray ionization can be efficiently detected using this technique. Impurities like mineral oils were detected easily in commercially available coconut oil, pointing the way to applications of social relevance. [ABSTRACT FROM AUTHOR]

Rationale Human health concerns have arisen for common bisphenols (BPA and BPS) as well as new structural analogs. While native sulfone bisphenols and sulfone-derivatized bisphenols are amenable to electrospray ionization (ESI), alternative ionization methods such as atmospheric pressure chemical ionization (APCI) and APPI were investigated to analyze non-derivatized, non-sulfone-containing bisphenols. Methods Ionization of bisphenols using negative ion APPI was compared to negative ion ESI and negative ion APCI for their relative abilities to produce [M−H]− precursor ions for subsequent collision-induced dissociation (CID) in a triple quadrupole mass analyzer. Multiple reaction monitoring (MRM) transitions were optimized using the most sensitive ion transitions and coupled with high-performance liquid chromatographic (HPLC) separation to detect and quantify BPA, BPB, BPF, BPZ, BPAP, BPS, and BPSIP. Results APPI provides a more universal sensitivity over ESI toward the classes of bisphenols studied with detection limits of 20-50 pg on-column. The LC/APPI-MS/MS method was used to examine the levels of these seven bisphenols in thermal paper receipts and in U.S. paper currency. In both receipts and currency, BPA and BPS were the dominant bisphenols found in the paper. Conclusions The measurement of BPA and bisphenol analogs in thermal paper receipts and transfer of bisphenols from receipts to currency notes is of increasing importance to assess human dermal exposure routes to this class of compounds. Equivalent sensitivity between sulfone- and non-sulfone-containing bisphenols is achievable through the use of alternate ionization sources such as APCI and APPI that circumvents tedious and time-consuming derivatization procedures to render analytical sensitivity by ESI. [ABSTRACT FROM AUTHOR]

Paper spray ionization mass spectrometry offers a rapid alternative platform requiring no sample preparation. Aerosolized chemical warfare agent (CWA) simulants trimethyl phosphate, dimethyl methylphosphonate, and diisopropyl methylphosphonate were captured by passing air through a glass fiber filter disk within a disposable paper spray cartridge. CWA simulants were aerosolized at varying concentrations using an in-house built aerosol chamber. A custom 3D-printed holder was designed and built to facilitate the aerosol capture onto the paper spray cartridges. The air flow through each of the collection devices was maintained equally to ensure the same volume of air sampled across methods. Each approach yielded linear calibration curves with R² values between 0.98-0.99 for each compound and similar limits of detection in terms of disbursed aerosol concentration. While the glass fiber filter disk has a higher capture efficiency (≈40%), the paper spray method produces analogous results even with a lower capture efficiency (≈1%). Improvements were made to include glass fiber filters as the substrate within the paper spray cartridge consumable. Glass fiber filters were then treated with ammonium sulfate to decrease chemical interaction with the simulants. This allowed for improved direct aerosol capture efficiency (>40%). Ultimately, the limits of detection were reduced to levels comparable to current worker population limits of 1 × 10-6 mg/m³. [ABSTRACT FROM AUTHOR]

Rationale Zero volt paper spray ionization (zvPSI) is a newly developed sample introduction/ionization technique for mass spectrometry (MS), which combines favorable features of paper spray ionization (PSI) and solvent-assisted inlet ionization (SAII). With a simple platform similar to PSI, zvPSI allows direct MS analysis of a broad type of samples (liquid, (semi-)solid, and imprint) without applying voltage. Methods In zvPSI-MS, a rectangular paper slip was used as a sample loader, extraction medium, and droplet emitter to introduce sample extract into the inlet of a mass spectrometer. For (semi-)solid and imprint samples, analyte(s) was directly extracted with solvent and instantaneously introduced into a mass spectrometer by aspiration. Solution samples were analyzed after being dried-up or by dispensing directly onto paper. Ionization was achieved by SAII and ionized molecules were detected by an ion-trap mass spectrometer. Results The developed method allowed direct voltage-free MS analysis of samples on filter paper substrate. Favorable features of PSI and SAII were successfully combined, such as fast data acquisition, flexible sample handlings, and direct extraction capability from solid samples (PSI), with no need for external high-voltage, laser, or nebulizing gas to convert analytes into gas-phase ions (SAII). Comparable to PSI and SAII, a wide variety of compounds such as amino acids, peptides, lipids and synthetic polymers were shown to be analyzed. Conclusions The developed method (zvPSI-MS) expanded the analytical utility of PSI and SAII to voltage-free direct MS analysis of a broad type of samples (liquid, (semi-)solid, and imprint). Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The analysis of catecholamines, such as dopamine, epinephrine and norepinephrine in urine can be used in the diagnosis of certain pathologies, such as hormone-producing tumors. Here, a fast and simple quantitative boronate affinity paper spray tandem mass spectrometric (PS-MS/MS) method is established, which can improve selectivity and reduce ion suppression without needing any instrumental chromatography. We use here the property of boronic acids, which can selectively bind ortho -diol-containing compounds under alkaline conditions. Paper tip modification and catechol enrichment protocols were developed to selectively bind, clean up and subsequently desorb such catecholamines. Standard catecholamine solutions, as well as human urine samples were analyzed with the PS-MS(/MS) method, which is fast, cheap and easy-to-operate compared to HPLC-MS/MS. Despite its high simplicity, boronate affinity PS-MS/MS exhibits good performance compared to HPLC-MS/MS in human urine analysis in terms of precision (2.1%–7.2% vs. 1.1%–2.9%) and accuracy (−10.2%–9.3% vs. −4.8%–5.1%), and a physiologically relevant limit of detection (0.027–0.12 μg mL−1). The boronate affinity PS-MS/MS clearly achieved the detection limits that would allow the fast analysis of urine samples for clinical purposes, such as screening for pheochromocytoma (exceeding 0.5 μg mL−1). [Display omitted] • Boronic acid-functionalized paper spray tips for selective catecholamine enrichment. • Boronate affinity paper spray MS/MS was developed for analysis of catecholamines. • Immediate pH buffering of urine samples by preloaded salts during extraction. • Fast extraction/analysis of catecholamines from urine shows clinical applicability. [ABSTRACT FROM AUTHOR]

With a great quantity of solid dosage tested by dissolution technology, developing a rapid and sensitive method to access the content of drug within dissolution media is highly desired by analysts and scientists. Traditionally, dissolution media is not compatible with mass spectrometry since the inorganic salts in the media might damage the mass spectrometer. Here, paper spray ionization mass spectrometry (PSI-MS), one of the ambient mass spectrometry technologies, is developed to characterize the content of drugs in dissolution media. The porous structure of paper can effectively retain salts from entering mass spectrometer. This makes the measurement of drug content within dissolution media by mass spectrometer possible. After the experimental parameters were optimized, calibration curves of model drugs − enalapril, quinapril and benazepril were established by using corresponding deuterated internal standards. PSI-MS was then deployed to characterize the content of enalapril from the dissolution testing of enalapril tablets. The results from PSI-MS are comparable to those from HPLC characterization. More importantly, the analysis time of 6 samples is shortened from 90 min to 6 min. Detection limit of enalapril maleate tablets by PSI-MS is 1/300 of LC. PSI-MS is rapid, sensitive and accurate in analyzing drug content from dissolution tests. [ABSTRACT FROM AUTHOR]

A rapid and direct paper spray ionization/mass spectrometry (PSI/MS) method was developed for quantitative analysis of ephedrine, pseudoephedrine, norpseudoephedrine, and methylephedrine in human urine. This method involves the use of a triangular filter paper and high-resolution mass spectrometry, where the molecular ions of ephedrines were generated by applying high voltage after loading the spray solvent to the paper which urine sample was pre-loaded. Small amounts (2 μL) of urine spiked with an internal standard were directly analyzed for ephedrines. The PSI/MS method was validated for linearity, within- and between-run precision, accuracy, and limit of detection. The results showed good linearity ( R 2 ≥ 0.9928) and acceptable precision and accuracy. Furthermore, the accuracy of the method was assessed by analyzing a blind urine sample from World Anti-Doping Agency and comparing the measured concentrations with the nominal concentrations. This test resulted in accuracies ranging from 96.4 to 106.1%, indicating that the PSI/MS method has the potential to be an alternative technique for the fast quantitation of ephedrines in doping control analysis. [ABSTRACT FROM AUTHOR]

On-surface photocatalytic degradation of Methylene Blue was conducted on a paper surface and the process continuously monitored using paper spray ionization mass spectrometry. Firstly, the photocatalyst (TiO 2 ) was immobilized on the paper surface, which was later cut in a triangle shape. A small amount of an aqueous solution of the dye Methylene Blue, used as a prototype target, was then added to the paper and the system exposed to UV-C radiation. Control experiments (photolysis) were also conducted, in which the paper surface contained no TiO 2 . All the processes were analyzed by paper spray mass spectrometry using lidocaine as internal standard, which was added to the paper just before analyzes. By measuring the intensities of the ions of m / z 284 (cationic Methylene Blue) and m / z 235 (protonated lidocaine) the performance of both processes (on-surface photocatalysis and photolysis) were compared. Photocatalysis showed a remarkable superior performance to degrade Methylene Blue in comparison to photolysis. The absorption of UV-C radiation by TiO 2 probably generated reactive species on the paper surface that caused faster dye degradation. In conclusion, paper spray ionization mass spectrometry proved to be a convenient platform where on-surface reactions can be promptly investigated. [ABSTRACT FROM AUTHOR]

Mass spectrometry imaging (MSI) is increasingly used to produce chemical images of latent fingerprints. Yet, the actual benefits of MSI for real case studies have to be assessed for fingerprints previously processed by forensic techniques. Here, we have evaluated the compatibility of desorption electrospray ionization (DESI) with the fingerprint enhancement technique involving Oil Red O (ORO). Methods: To optimize the ionization step independently from surface extraction, the ORO reagent and its mixture with model compounds (triolein and linoleic acid) were first studied in solution using high-resolution electrospray ionization tandem mass spectrometry (ESI-MS/MS). Then, DESI-MSI experiments were performed in both polarity modes for ORO-processed fingermarks deposited on pieces of paper used as porous substrates. Results: ESI-MS of ORO reveals a complex mixture of azo dyes. Two main impurities detected beside the targeted species were characterized using MS/MS and then were usefully employed to produce DESI-MS images of fingermarks, decreasing the scanning rate to get sufficient ion abundance from natural fingerprints. ORO did not prevent chemical profiling, and one major added value of this pink dye was to produce MS images with contrast that cannot be obtained optically for some colored substrates. Conclusions: DESI-MS has demonstrated imaging compatibility with the application of ORO used to enhance latent fingerprints on paper and could also enable chemical profiling in natural fingermarks. In addition, MS images of ORO impurities were of higher quality than optical ones for fingerprints revealed on colored paper. [ABSTRACT FROM AUTHOR]

We have developed nanoparticle-embedded paper-spray mass spectrometry for studying three types of heterogeneously catalyzed reactions: 1) Palladium-nanoparticle-catalyzed Suzuki cross-coupling reactions, 2) palladium- or silver-nanoparticle-catalyzed 4-nitrophenol reduction, and 3) gold-nanoparticle-catalyzed glucose oxidation. These reactions were almost instantaneous on the nanocatalyst-embedded paper, which subsequently transferred the transient intermediates and products to a mass spectrometer for their detection. This in situ method of capturing transient intermediates and products from heterogeneous catalysis is highly promising for investigating the mechanism of catalysis and rapidly screening catalytic activity under ambient conditions. [ABSTRACT FROM AUTHOR]

Paper-based microfluidic channels were created from solid wax printing, and the resultant 2D wax-printed paper substrates were used for paper spray (PS) mass spectrometry (MS) analysis of small organic compounds. Controlling fluid flow at the tip of the wax-printed paper triangles enabled the use of lower spray voltages (0.5–1 kV) and extended signal lifetime (10 minutes) in PS-MS. High sensitivity (sub ng mL−1 levels) and quantitation precision (＜10% RSD) have been achieved in the analysis of illicit drugs in 4 μL of raw urine (fresh and dry), as well as corrosion inhibitors and pesticides in water samples. The reported study encourages the future development of disposable 3D microfluidic paper-based analytical devices, which function with simple operation but capable of on-chip analyte detection by MS; such a device can replace the traditional complex laboratory procedures for MS analysis to enable on-site in situ sampling with portable mass spectrometers. [ABSTRACT FROM AUTHOR]

New faster and simpler methods for determination of pesticides in agricultural products are necessary as requirements for food safety are becoming increasingly stringent. One possibility is to introduce a fast, easy and low-cost screening method before liquid chromatography mass spectrometry analyses. We hereby present a systematic proof of concept study of paper spray mass spectrometry method for pesticide detection as a screening method. Two sampling approaches – wiping the surface with paper and applying the sample homogenate directly on the paper – were used. The wiping method was more extensively studied for imazalil and thiabendazole originally present in oranges. For homogenized samples three matrices – oranges, tomatoes and grapes – and five pesticides of different chemical nature and polarity – thiabendazole, aldicarb, imazalil, methomyl and methiocarb – were chosen. It has been shown that limits of detection below maximum residue levels can be achieved for both methods (e.g. imazalil and thiabendazole detection limits were found to be lower than 5 mg/kg). The methods are therefore suitable for fast screening of samples. Moreover, the wiping method was also applied for 11 samples – oranges, grapefruits, lemons, limes, mandarins, tomatoes, apples, pears, strawberries, grapes and sweet peppers – from the local supermarket to screen for different pesticides. Three positive samples for thiabendazole and imazalil and one positive sample for imazalil were found. [ABSTRACT FROM AUTHOR]

Although the theoretical capacity of silicon is ten times higher than that of graphite, the overall electrode capacity of Si anodes is still low due to the low Si loading and heavy metal current collector. Here, a novel flexible 3D Si/C fiber paper electrode synthesized by simultaneously electrospraying nano-Si-PAN (polyacrylonitrile) clusters and electrospinning PAN fibers followed by carbonization is reported. The combined technology allows uniform incorporation of Si nanoparticles into a carbon textile matrix to form a nano-Si/carbon composite fiber paper. The flexible 3D Si/C fiber paper electrode demonstrate a very high overall capacity of ≈1600 mAh g-1 with capacity loss less than 0.079% per cycle for 600 cycles and excellent rate capability. The exceptional performance is attributed to the unique architecture of the flexible 3D Si/C fiber paper, i.e., the resilient and conductive carbon fiber network matrix, carbon-coated Si nanoparticle clusters, strong adhesion between carbon fibers and Si nanoparticle clusters, and uniform distribution of Si/C clusters in the carbon fiber frame. The scalable and facile synthesis method, good mechanical properties, and excellent electrochemical performance at a high Si loading make the flexible 3D Si/C fiber paper batteries extremely attractive for plug-in electric vehicles, flexible electronics, space exploration, and military applications. [ABSTRACT FROM AUTHOR]

Representation of mass spectrometry analysis with paper spray ionization using different solvents in araticum samples. [Display omitted] • Different araticum fruit parts were evaluated for their chemical profile. • Three solvents were tested; • The fruit, in general, is composed of acetogenins and alkaloids; • The ethanol solvent extracted a more significant number of compounds; • The global evaluation showed that the samples are grouped by the part of the fruit studied regardless of the solvent. The Brazilian cerrado is considered one of the most critical biomes in the world. Araticum (Annona crassiflora Mart.) is a native plant from the Brazilian cerrado, abundant in nutrients and highly energetic. This study aimed to obtain chemical fingerprints of different parts of the araticum fruit, i.e. pulp, peel, and seed. Extracts from these three parts were prepared using different solvents (ethanol, water, and mixtures of ethanol and water) and later analyzed by paper spray ionization mass spectrometry. In general, ethanol extracted more metabolites than the other solvents. The chemical profiles varied according to the fruit part, geographic location, and extractor solvent. Among the metabolites, acetogenins (62.3%) and alkaloids (20.7%) predominated. Principal component analyses revealed that the samples were grouped according to the fruit part, regardless of the extractor solvent used. Araticum shows remarkable potential due to the beneficial properties of the metabolites for human health. The insertion of araticum in the human diet is still underexplored but is a promising alternative. [ABSTRACT FROM AUTHOR]

Paper spray mass spectrometry is a method for the direct analysis of biofluid samples in which extraction of analytes from dried biofluid spots and electrospray ionization occur from the paper on which the dried sample is stored. We examined matrix effects in the analysis of small molecule drugs from urine, plasma, and whole blood. The general method was to spike stable isotope labeled analogs of each analyte into the spray solvent, while the analyte itself was in the dried biofluid. Intensity of the labeled analog is proportional to ionization efficiency, whereas the ratio of the analyte intensity to the labeled analog in the spray solvent is proportional to recovery. Ion suppression and recovery were found to be compound- and matrix-dependent. Highest levels of ion suppression were obtained for poor ionizers (e.g., analytes lacking basic aliphatic amine groups) in urine and approached -90%. Ion suppression was much lower or even absent for good ionizers (analytes with aliphatic amines) in dried blood spots. Recovery was generally highest in urine and lowest in blood. We also examined the effect of two experimental parameters on ion suppression and recovery: the spray solvent and the sample position (how far away from the paper tip the dried sample was spotted). Finally, the change in ion suppression and analyte elution as a function of time was examined by carrying out a paper spray analysis of dried plasma spots for 5 min by continually replenishing the spray solvent. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Recent years have witnessed a surge in the application of microrobots within the medical sector, with hydrogel microrobots standing out due to their distinctive advantages. These microrobots, characterized by their exceptional biocompatibility, adjustable physico-mechanical attributes, and acute sensitivity to biological environments, have emerged as pivotal tools in advancing medical applications such as targeted drug delivery, wound healing enhancement, bio-imaging, and precise surgical interventions. The capability of hydrogel microrobots to navigate and perform tasks within complex biological systems significantly enhances the precision, efficiency, and safety of therapeutic procedures. Firstly, this paper delves into the material classification and properties of hydrogel microrobots and compares the advantages of different hydrogel materials. Furthermore, it offers a comprehensive review of the principal categories and recent innovations in the synthesis, actuation mechanisms, and biomedical application of hydrogel-based microrobots. Finally, the manuscript identifies prevailing obstacles and future directions in hydrogel microrobot research, aiming to furnish insights that could propel advancements in this field. [ABSTRACT FROM AUTHOR]

In this paper, urethane-based acrylates (UA) were prepared via an environmentally friendly non-isocyanate route. Isophorone diamine (IPDA) reacted with ethylene carbonate (EC), producing carbamate containing amine and hydroxyl groups, which further reacted with neopentyl glycol diacrylate (NPGDA) by aza Michael addition, forming UA. The structures of the obtained intermediates and UA were characterized by 1H NMR and electrospray ionization high-resolution mass spectrometry (ESI-HRMS). The photopolymerization kinetics of UA were investigated by infrared spectroscopy. The composite with obtained UA can be UV cured quickly to form a transparent film with a tensile strength of 21 MPa and elongation at break of 16%. After UV curing, the mono-functional urethane acrylate was copolymerized into the cross-linked network in the form of side chains. The hydroxyl and carbamate bonds on the side chains have high mobility, which make them easy to form stronger dynamic hydrogen bonds during the tensile process, giving the material a higher tensile strength and elongation at break. Therefore, the hydrogen bonding model of a cross-linked network is proposed. The composite with UA can be 3D printed into models. [ABSTRACT FROM AUTHOR]

Over the years, there has been notable progress in understanding the pathogenesis and treatment modalities of diabetes and its complications, including the application of metabolomics in the study of diabetes, capturing attention from researchers worldwide. Advanced mass spectrometry, including gas chromatography–tandem mass spectrometry (GC-MS/MS), liquid chromatography–tandem mass spectrometry (LC-MS/MS), and ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS), etc., has significantly broadened the spectrum of detectable metabolites, even at lower concentrations. Advanced mass spectrometry has emerged as a powerful tool in diabetes research, particularly in the context of metabolomics. By leveraging the precision and sensitivity of advanced mass spectrometry techniques, researchers have unlocked a wealth of information within the metabolome. This technology has enabled the identification and quantification of potential biomarkers associated with diabetes and its complications, providing new ideas and methods for clinical diagnostics and metabolic studies. Moreover, it offers a less invasive, or even non-invasive, means of tracking disease progression, evaluating treatment efficacy, and understanding the underlying metabolic alterations in diabetes. This paper summarizes advanced mass spectrometry for the application of metabolomics in diabetes mellitus, gestational diabetes mellitus, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic encephalopathy, diabetic cardiomyopathy, and diabetic foot ulcers and organizes some of the potential biomarkers of the different complications with the aim of providing ideas and methods for subsequent in-depth metabolic research and searching for new ways of treating the disease. [ABSTRACT FROM AUTHOR]