Paper Spray Mass Spectrometry Research Articles

Approaches for posaconazole therapeutic drug monitoring and their clinical benefits.

This review examines the progress of research on posaconazole therapeutic drug monitoring (TDM) that has focused on differences in the TDM of posaconazole after clinical application in different formulations and in different populations, the factors that affect posaconazole concentrations, the advantages of posaconazole TDM in terms of clinical efficacy and cost savings, and measurement methods. A literature search (2006 to 2024) was performed in PubMed and Embase with the following search terms: noxafil, posaconazole hydrate, posaconazole, drug monitoring, therapeutic drug monitoring, and TDM. Abstracts of review articles, prospective studies, and retrospective studies were reviewed. TDM should be implemented earlier for posaconazole tablets and injections than for oral posaconazole suspensions. Posaconazole TDM is beneficial for improving clinical efficacy, and the incidence of breakthrough invasive fungal infections (IFIs) can be significantly reduced by gradually adjusting the posaconazole dose in response to TDM in patients with inadequate trough concentrations. Early TDM allows more patients to achieve target therapeutic posaconazole concentrations. TDM can also facilitate dose adjustments, which reduce the cost of this expensive drug. Different assay techniques, including chromatography, microbiological detection, chemofluorimetry, paper spray mass spectrometry, and capillary electrophoresis, can be used for posaconazole TDM. Posaconazole TDM has potential clinical utility and cost-saving benefits and could improve the outcomes of IFI treatment.

Antinociceptive, anti-inflammatory, and antioxidant effects of a flavonoid-rich phytocomplex from the leaves of Celtis iguanaea (jacq.) Sargent (Cannabaceae)

We demonstrated the antinociceptive and anti-inflammatory effects of the ethyl acetate leaf extract of Celtis iguanaea (Jacq.) Sargent (EAECi) in mice. The in vitro antioxidant activity of EAECi and its phytoconstituents was also investigated. The antinociceptive effect of EAECi is attributed to its anti-inflammatory activity, as evidenced by its anti-hyperalgesic and antiedematogenic effects. EAECi reduced polymorphonuclear cell migration, myeloperoxidase activity, pro-inflammatory cytokines (TNF-α and IL-1β), and PGE2 levels. The levels of anti-inflammatory cytokines (IL-4 and IL-10) were increased compared to the vehicle-treated groups. The overall antioxidant capacity of EAECi is noteworthy, with the Electrochemical Index determined by Differential Pulse Voltammetry being 42.7 μA/V. Concurrently, Square Wave Voltammetry revealed the reversibility of the redox process (Ep1a/Ep1c) at 0.254 V. The presence of twenty-six phytochemicals, primarily flavone aglycones, was suggested by paper-spray mass spectrometry. These findings represent a step towards validating C. iguanaea leaf extract for treating acute inflammatory conditions.

IMPACT: Innovative (nano)Materials and processes for advanced catalytic technologies to degrade PFOA in water

We hereby report the development of a novel electrochemical method to degrade perfluorooctanoic acid (C7F15COOH, PFOA). At the center of the approach are bimetallic Pd–Ru nano-catalyst materials called IMPACT: Innovative (nano)Materials and Processes for Advanced Catalytic Technologies. IMPACT uses flavonoid-sequestered Pd–Ru, allowing the development of specialized electrodes with tunable properties to sequentially degrade PFOA in wastewater samples into a sustainable byproduct via an indirect electrochemical method. Electron transfers at RuOxHy species stabilize the Pd component of the nano-catalysts, enabling the degradation process via PFOA deprotonation, chain shortening, decarboxylation, hydrolysis, fluoride elimination, and CF2 flake-off mechanism. IMPACT enabled the observation of redox peaks at −0.26 V and 0.56 V for the first time, with accompanying reduction peaks at −0.5V and 0.29 V, respectively. These redox peaks, which correlated with the concentrations of PFOA (20, 50, 100, 200, and 400.mg L−1), were verified and confirmed using electrochemical simulations. Control experiments did not show degradation of PFOA in the absence of Pd–Ru nano-catalyst. The degradation in wastewater was obtained within 3 h with an efficiency of 98.5%. The electrochemical degradation products of PFOA were identified using High-resolution desalting paper spray mass spectrometry (DPS-MS) and collision-induced dissociation (CID) analysis. The results yielded C2F5COOH, C3F7COOH, and C6F13OH with dissociation losses of CF2O or CO2. IMPACT introduces a novel nano-catalyst with high efficiency and a reliable capability that defluorinates strong C–F bonds that are components of recalcitrant organics in myriad environmental matrices.

Phenolic Compounds Characterization of Caryocar brasiliense Peel with Potential Antioxidant Activity.

The pequi (Caryocar brasiliense) fruit peel, despite being frequently discarded, has a high content of bioactive compounds, and therefore has a high nutritional value. The present study aimed to explore the bioactivities in the pequi peel, particularly their potential health benefits at the level of antioxidant activity. The exploitation of this fruit could also present significant economic benefits and applications of pequi by-products would represent a reduction in waste, having a positive impact on the environment. Phenolic compounds present in the pequi exocarp and external mesocarp were identified by paper spray mass spectrometry (PS-MS) and quantified by HPLC. The total phenolic content (TPC) along with the amount of 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and the amount of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) were also determined in peel extracts. Epicatechin was the most abundant phenolic compound found, followed by the caffeic, salicylic, and gallic acids. In addition, fingerprinting revealed compounds related to several beneficial health effects. In short, the results obtained were encouraging for potential applications of pequi peel in the field of functional foods.

Furfural analysis of aqueous and oily foodstuffs using a single modified paper for combined headspace extraction, derivatization and paper spray mass spectrometry

Furfurals, including 2-furaldehyde, 5-methylfurfural and 5-hydroxymethylfurfural, widely exist in carbohydrate-rich daily foods, and may have toxic effects on humans. Here, a new headspace extraction-paper spray mass spectrometry (HSPS-MS/MS) method was established for furfural detection, in which the extraction and derivatization of volatiles with pre-loaded derivatization agent on paper tips is combined with paper spray mass spectrometry for detection. By this simple and cheap approach, interference of non-volatile matrix compounds is prevented, and the derivatization agent improves electrospray-type ionization efficiency, thus increasing selectivity and sensitivity. The approach was optimized, by investigating positioning during extraction, extraction duration, derivatization agent, addition of internal standard for quantification and finally validated. For this, the developed method was benchmarked against HPLC-UV and could obtain detections limits of 0.32–0.40 μg mL−1 for 2-furaldehyde, 5-methylfurfural and 5-hydroxymethylfurfural in olive oil. Moreover, fast screening of free furfurals in soy sauce, coffees and teas was demonstrated with the HSPS-MS/MS method.

Tentative identification of phytochelatins, their derivatives, and Cd-phytochelatin complexes in Ocimum basilicum L. roots by Paper Spray Mass Spectrometry.

An unprecedented and direct PS-MS (paper spray ionization mass spectrometry) method was proposed for the detection of native peptides, that is, glutathiones (GSHs), homoglutathiones (hGSHs), and phytochelatins (PCs), in basil (Ocimum basilicum L.) roots before and after cadmium exposure. The roots were submitted to cold maceration followed by sonication with formic acid as the extractor solvent for sample preparation. PS-MS was used to analyze such extracts in the positive mode, and the results allowed for the detection of several GSHs, hGSHs, and PCs. Some of these PCs were not distinguished in the control samples, that is, basil roots not exposed to cadmium. Other PCs were noticed in both types of roots, uncontaminated and cadmium-contaminated, but the intensities were higher in the former samples. Moreover, long-time exposure to cadmium stimulated the formation of some of these PCs and their cadmium complexes. The results, therefore, provided some crucial insights into the defense mechanism of plants against an external stress condition due to exposure to a toxic heavy metal. The present study represents a promising alternative to investigate other crucial physiological processes in plants submitted to assorted stress conditions.

The Open SprayBot: A high-throughput paper spray mass spectrometry platform for disease screening

Newborn disease screening increases survival, improves quality of life and reduces treatment costs for healthcare systems. Mass spectrometry (MS) is an effective method for metabolic screening. However, conventional analytical methods require biofluid handling and cooling conditions during transport, making the logistics difficult and expensive, especially for remote regions. ’Paper-spray’ (PS) ionization generates a charged solvent spray from samples deposited on paper strips. Therefore, samples can be applied on a suitable matrix and shipped as dried spots to diagnostic laboratories with standard postal or messenger services. We built a robotic platform, the ’Open SprayBot’, to automatically analyze paper-deposited samples via PS-MS and increase the sample throughput. The system is operated via RUMBA32 and Arduino Mega boards. A commercial syringe pump and power supply provide solvent application and electrical current required for PS-MS. The usability of the Open SprayBot was demonstrated by quantifying palmitoyl-l-carnitine, a common biomarker in newborn screening.

Detecting the therapeutic drugs in blood samples through PDMS-printed paper spray mass spectrometry

In this paper, paper microfluidic channel fabricated by directly screen-printing of polydimethylsiloxane (PDMS) is proposed for paper spray mass spectrometry analysis of therapeutic drugs in the blood samples. Compared with traditional paper spray, PDMS-printed paper spray (PP-PS) allows fluid to flow to the tip of paper with less sample loss which significantly improved the signal intensity of target compounds in blood samples. As paper can reduce the matrix effect, PP-PS also has a greater advantage than electro-spray Ionization (ESI) when directly analyzing complex biological sample in terms of the detection efficiency. Linearity and limits of detection (LOD) were evaluated for five psychotropic drugs: olanzapine, quetiapine, 9-hydroxyrisperidone, clozapine, risperidone. As a result, PP-PS improved the signal intensity of the psychotropic drugs at a concentration of 250 ng/ml in blood samples by a factor of 2–5 times and lowered the relative standard deviation (RSD) by a factor of 2–5.6 times compared with traditional paper spray. And PP-PS also improved signal intensity by a factor of 9–33 times compared with ESI. Quantitative experiments of PP-PS mass spectrometry indicated that the linear range was 5–500 ng/ml and the LOD were improved by a factor of 5–71 times for all these drugs compared with traditional paper spray. In addition, PP-PS was applied to the home-made miniaturized mass spectrometer and the precursor ions of all five psychotropic drugs (250 ng/ml) in the mass spectrometry results were obtained as well. These could prove that PP-PS has the potential to analyze complex biological samples in application on the miniaturized mass spectrometer which can be used outside the laboratory.

Combining surface-enhanced Raman spectroscopy (SERS) and paper spray mass spectrometry (PS-MS) for illicit drug detection

There is an ongoing effort in the US illicit drug market to make new psychoactive compounds more potent and addictive. Due to continuous chemical modifications, many fentanyl analogs are developed and mixed with more traditional illicit drugs, such as cocaine and heroin. Detecting fentanyl and fentanyl analogs in these illicit drug mixtures has become more crucial because of the increased potency and associated health risks. Most confirmatory procedures require time-consuming and expensive, highly sophisticated laboratory equipment and experimental procedures, which can delay critical information that might save a victim or find a suspect. In this study, we propose miniaturizing and accelerating this process by combining surface-enhanced Raman spectroscopy (SERS) analysis and paper spray mass spectrometry (PS-MS). For this aim, dual-purposed paper substrates were developed through soaking in Au/Ag nanostars suspensions. These novel, in-house prepared paper SERS substrates showed stability for up to four weeks with and without the presence of drug compounds. Fentanyl analogs with similar SERS spectra were differentiated by coupling with PS-MS. The limit of detection (LOD) for fentanyl on the paper substrates is 34 μg/mL and 0.32 μg/mL for SERS and PS-MS, respectively. Fentanyl and fentanyl analogs show selective SERS enhancement that helped to detect trace amounts of these opioids in heroin and cocaine street samples. In short, we propose the combination of SERS/PS-MS by using modified paper substrates to develop cost-effective, sensitive, rapid, portable, reliable, and reproducible methods to detect illicit drugs, especially trace amounts of fentanyl and fentanyl analogs in illicit drug mixtures. The combination of these two category A techniques allows for the identification of illicit drugs according to the SWGDRUG guidelines.

Paper Spray Mass Spectrometry with On‐Paper Electrokinetic Manipulations: Part‐Per‐Trillion Detection of Per/Polyfluoroalkyl Substances in Water and Opioids in Urine

AbstractWe 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.

Paper Spray Mass Spectrometry with On-Paper Electrokinetic Manipulations: Part-Per-Trillion Detection of Per/Polyfluoroalkyl Substances in Water and Opioids in Urine.

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.

Rapid and simultaneous determination of curcuminoids and gingerols in food products containing turmeric and ginger using paper spray mass spectrometry.

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.

Rapid discrimination of geographical origin of garlic (Allium sativum L.): A metabolomic approach applied to paper spray mass spectrometry data.

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. 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. 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. 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.

Plasma drug screening using paper spray mass spectrometry with integrated solid phase extraction.

Drug overdoses have risen dramatically in recent years. We developed a simple nontargeted method using a disposable paper spray cartridge with an integrated solid phase extraction column. This method was used to screen for ~160 fentanyl analogs, synthetic cannabinoids, other synthetic drugs, and traditional drugs of abuse in over 300 authentic overdose samples collected at emergency departments in Indianapolis. A solid phase extraction step was implemented on the paper spray cartridge to enable subnanograms per milliliter synthetic drugs screening in plasma. Analysis was performed on a quadrupole orbitrap mass spectrometer using the sequential window acquisition of all theoretical fragment ion spectra approach in which tandem mass spectrometry was performed using 7 m/z isolation windows in the quadrupole. Calibration curves with isotopically labeled internal standards were constructed for 35 of the most frequently encountered synthetic and traditional illicit drugs by US toxicology labs. Additional qualitative-only drugs in a suspect screening list were also included. Limits of detection in plasma for synthetic cannabinoids ranged from 0.1 to 0.5 and 0.1 to 0.3ng/mL for fentanyl and its analogs and between 1 and 5ng/mL for most other drugs. Relative matrix effects were evaluated by determining the variation of the calibration slope in 10 different lots of biofluid and found to be between 3% and 20%. The method was validated on authentic overdose samples collected from two emergency departments in Indianapolis, Indiana, from suspected or known overdoses. Commonly detected synthetic drugs included fentanyl related substances, designer benzodiazepines such as flubromazolam, and the synthetic cannabinoid 5F-PB-22.

Influence of the Different Maturation Conditions of Cocoa Beans on the Chemical Profile of Craft Chocolates.

Cocoa beans (Theobroma cacao L.) can be used for craft chocolate production, which arouses consumer interest due to their perceived better quality. This study aimed to evaluate the chemical profile of 80% artisanal chocolate samples produced with cocoa beans subjected to different maturation conditions. In the first maturation process, beans were matured under no-oxygen conditions, and in the second, the toasted beans were matured in oak barrels. The volatile compounds of the chocolate samples were extracted by the solid-phase microextraction method in headspace mode and analyzed by gas chromatography/mass spectrometer. The non-volatile compounds were extracted with methanol and analyzed through paper spray mass spectrometry. Overall, 35 volatile compounds belonging to different chemical classes (acids, alcohols, aldehydes, ketones, esters, and pyrazines) were identified, such as propanoic acid and butane-2,3-diol. In addition, 37 non-volatile compounds, such as procyanidin A pentoside and soyasaponin B, were listed. Tannins, flavonoids, and phenylpropanoids were the main chemical classes observed, varying between the two samples analyzed. Therefore, it was possible to verify that maturation conditions affected the metabolomic profile of the 80% artisanal chocolate samples, being able to influence the sensory characteristics and bioactive compounds profile. Given these results, the sensory evaluation of these chocolates is suggested as the next step.

Enhanced Compound Analysis Using Reactive Paper Spray Mass Spectrometry: Leveraging Schiff Base Reaction for Amino Acid Detection.

Paper spray mass spectrometry (PS-MS) has evolved into a promising tool for monitoring reactions in thin films and microdroplets, known as reactive PS, alongside its established role in ambient and direct ionization. This study addresses the need for rapid, cost-effective methods to improve analyte identification in biofluids by leveraging reactive PS-MS in clinical chemistry environments. The technique has proven effective in derivatizing target analytes, altering hydrophobicity to enhance elution and ionization efficiency, and refining detection through thin-film reactions on paper, significantly expediting reaction rates by using amino acids (AAs) as model analytes. These molecules are prone to interacting with substrates like paper, impeding elution and detection. Additionally, highly abundant species in biofluids, such as lipids, often suppress AA ionization. This study employs the Schiff base (SB) reaction utilizing aromatic aldehydes for AA derivatization to optimize reaction conditions time, temperature, and catalyst presence and dramatically increasing the conversion ratio (CR) of formed SB. For instance, using leucine as a model AA, the CR surged from 57% at room temperature to 89% at 70 °C, with added pyridine during and after 7.5 min, displaying a 43% CR compared to the bulk reaction. Evaluation of various aromatic aldehydes as derivatization agents highlighted the importance of specific oxygen substituents for achieving higher conversion rates. Furthermore, diverse derivatization agents unveiled unique fragmentation pathways, aiding in-depth annotation of the target analyte. Successfully applied to quantify AAs in human and rat plasma, this reactive PS-MS approach showcases promising potential in efficiently detecting conventionally challenging compounds in PS-MS analysis.

Therapeutic drug monitoring of clozapine in human serum by high-throughput paper spray mass spectrometry

IntroductionMonitoring the atypical antipsychotic drug clozapine is crucial to ensure patient safety. This article showcases a high-throughput analytical method for measuring clozapine and its primary metabolite norclozapine (N-desmethylclozapine) in serum using paper spray mass spectrometry (PS-MS). ObjectivesThis study aimed to assess the viability of a PS-MS method for the rapid measurement of clozapine and norclozapine in human serum samples as an alternative to liquid chromatography mass spectrometry (LC-MS). MethodsSerum samples were processed by protein precipitation followed by deposition of the supernatant containing labelled internal standards onto paper spray substrates mounted in cartridges. Analytes were then analyzed using a triple quadrupole mass spectrometer equipped with a commercial paper spray ionization source. The results obtained from the patient samples were compared to those from a validated LC-MS assay. ResultsPS-MS calibrations for clozapine and norclozapine were linear (R2 > 0.99) over five days. Between-run precision was below 8 %, and within-run precision did not exceed 10 %. When compared to a validated LC-MS method, the mean bias for 39 patient samples was −9% for clozapine and −1% for norclozapine, with no outliers. Mass spectrometry ion ratio comparisons indicated no interference for patient samples above the lower limit of quantification. There was less than 7 % change in the measured concentrations of both analytes over five days for samples dried on paper substrates. Notably, virtually no maintenance of the MS source was required during this study. ConclusionThis study illustrates the potential of PS-MS for serum drug monitoring in the clinical laboratory.

In Situ Oral Metabolism Analysis of Astringent Compounds in Tea by Paper Spray Mass Spectrometry, Electrospray Mass Spectrometry, Turbidimetry, and Sensory Evaluation.

The phenolic compounds (PCs) are the primary components responsible for the astringency of tea infusions, and this astringency is intricately linked to the in situ oral metabolism of PCs in saliva. Initially, a total of 54 PCs were identified in tea infusions by electrospray mass spectrometry (ESI-MS). Subsequently, an in vivo metabolism analysis of PCs during varying drinking times and oral locations was conducted by both paper spray mass spectrometry (PS-MS) and sensory evaluation. The metabolism of PCs within oral saliva was a prolonged process, the residual PCs were distributed across diverse oral regions after drinking tea infusion, and the higher residual PC content reflected the stronger astringency intensity. Furthermore, an in vitro metabolism analysis of PCs under varied reaction temperatures and durations was performed by ESI-MS and turbidimetry. As the reaction time extended, more PCs in tea was interacting with saliva. Moreover, the higher temperatures facilitated this interaction between PCs and saliva. Therefore, this investigation establishes a foundation for further elucidating the mechanisms underlying astringency formation.

Rapid detection of per- and polyfluoroalkyl substances (PFAS) using paper spray-based mass spectrometry

Traditional PFAS analysis by mass spectrometry (MS) is time-consuming, as laborious sample preparation (e.g., extraction and desalting) is necessary. Herein, we report fast detection of PFAS by paper spray (PS)-based MS techniques, which employs a triangular-shaped filter paper for sample loading and ionization (≤ 3 min per sample). In this study, PS-MS was first used for direct PFAS analysis of drinking water, tap water, and wastewater. Interestingly, food package paper materials can be directly cut and examined with PS-MS for possible PFAS contamination. For samples containing salt matrices which would suppress PFAS ion signal, desalting paper spray mass spectrometry (DPS-MS), was shown to be capable of rapidly desalting, ionizing and detecting PFAS species such as per-fluorooctanoic acid (PFOA) and per-fluorosulphonic acid (PFOS). The retention of PFAS on paper substrate while salts being washed away by water is likely due to hydrophilic interaction between the PFAS polar head (e.g., carboxylic acid, sulfonic acid) with the polar filter paper cellulose surface. The DPS-MS method is highly sensitive (limits of detection:1.2–4.5 ppt) and can be applicable for directly analyzing soil extract and soil samples. These results suggest the high potential of PS-MS and the related DPS-MS technique in real-world environmental analysis of PFAS.

Paper spray mass spectrometry combined with machine learning as a rapid diagnostic for chronic kidney disease.

A new analytical method for chronic kidney disease (CKD) detection utilizing paper spray mass spectrometry (PS-MS) combined with machine learning is presented. The analytical protocol is rapid and simple, based on metabolic profile alterations in urine. Anonymized raw urine samples were deposited (10 μL each) onto pointed PS-MS sample strips. Without waiting for the sample to dry, 75 μL of acetonitrile and high voltage were applied to the strips, using high resolution mass spectrometry measurement (15 s per sample) with polarity switching to detect a wide range of metabolites. Random forest machine learning was used to classify the resulting data. The diagnostic performance for the potential diagnosis of CKD was evaluated for accuracy, sensitivity, and specificity, achieving results >96% for the training data and >91% for validation and test data sets. Metabolites selected by the classification model as up- or down-regulated in healthy or CKD samples were tentatively identified and in agreement with previously reported literature. The potential utilization of this approach to discriminate albuminuria categories (normo, micro, and macroalbuminuria) was also demonstrated. This study indicates that PS-MS combined with machine learning has the potential to be used as a rapid and simple diagnostic tool for CKD.