Efficient ofloxacin degradation via photo-Fenton process over eco-friendly MIL-88A(Fe): Performance, degradation pathways, intermediate library establishment and toxicity evaluation.

The high-throughput production of the eco-friendly MIL-88A(Fe) was achieved under mild reaction conditions with normal pressure and temperature. The as-prepared MIL-88A(Fe) exhibited efficient photo-Fenton catalytic ofloxacin (OFL) degradation upon visible light irradiation with good stability and reusability. The OFL (20.0 mg/L) was completely degraded within 50 min under visible light with the aid of MIL-88A(Fe) (0.25 g/L) and H2O2 (1.0 mL/L) in aqueous solution (pH = 7.0). The hydroxyl radicals (·OH) are the main active species during the photo-Fenton oxidation process. Meanwhile, the degradation intermediates and the corresponding degradation pathways were identified and proposed with the aid of both ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and density functional theory (DFT) calculations. Finally, the degradation product library was firstly established to identify intermediate transformation products (TPs) with their variation of concentration, and their corresponding toxicologic activities were assessed via Toxtree and T.E.S.T software as well. Finally, the MIL-88A is efficient and stable with four cycles' catalysis operations, demonstrating good potential for water treatment.

Supercritical Fluid Extraction Combined with Ultrahigh Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry for Determination of Extractables to Evaluate Compatibility of Drugs with Rubber Closures.

Biological activity and pharmacological efficacy of protein drugs may be affected by the compatibility between drug and packaging materials. The compatibility of rubber closures seal cap has become the focus of many studies due to its complicated formulation. Despite of the significance of the issue, currently, there is little available data about organic leachables in drugs which is also not comprehensive. Since the concentration of migrants in drug is usually low and the matrix is complicated, the establishment of overall profile of extractables is crucial for the characterization of leachables. Herein, the supercritical fluid extraction (SFE) method was used because of its great extraction capacity and efficiency for low to medium polar extractables in rubber stoppers. The SFE conditions were optimized by response surface methodology (RSM). Experimental results of the extract yield were close to the predicted values (R2 = 0.95). Then the extractables were qualitatively and quantitatively analyzed with ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Finally, risk assessment was made by comparing predicted exposure with injection permitted daily exposure (pPDE) limit or threshold recommended by threshold of toxicological concern (TTC). The results showed that there are many extractables such as glyceride, fatty acids and derivatives, antioxidants, and degradation products. Among them degradation products were in the majority and content of 17 substances exceeded corresponding limits. Considering their unknown toxicology, more experiments are therefore needed to provide information on their toxicology and risk assessment. The study provides a reference for the compatibility of drugs, and quality supervision of pharmaceuticals packaging.

Ultra-high performance supercritical fluid chromatography combined with quadrupole time-of-flight mass spectrometry for the characterization of pentaerythritol fatty acid esters.

RATIONALE: Pentaerythritol fatty acid esters are an excellent lubricant oil additive, due to their good biodegradability, thermal ability, anti-wear, and friction properties. However, to meet the application requirements, fatty acids with different alkyl chain lengths are reacted with pentaerythritol, resulting in complex ester compositions. To reveal the relation between the functionalities and the composition of esters, it is important to develop a method for their analysis. METHODS: We developed a method using ultra-high-performance supercritical fluid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPSFC/QTOF-MS) to separate and characterize pentaerythritol fatty acid esters. This method has the advantages such as short analysis time and high separation efficiency for such weakly polar compounds; high-resolution mass spectrometry (HRMS) provides exact mass information, enabling the identification of the structure of the pentaerythritol fatty acid esters. RESULTS: Based on the exact masses and characteristic ions, the pentaerythritol fatty acid esters and their main fragmentation pathways were identified; the fatty acid composition was also deduced from characteristic product ions. A dihydrogen rearrangement reaction caused the neutral loss of fatty acid fragment; [M + Na-FA]+ product ions (a stable six-member ring structure) were produced due to the absence of a γ hydrogen in pentaerythritol fatty acid esters. CONCLUSIONS: A UHPSFC/QTOF-MS method was successfully employed for the separation of pentaerythritol fatty acid esters. Exact masses and product ion information were determined using HRMS. The composition of the fatty acids was effectively deduced by characteristic ions and their relative abundances. This method is an effective means for the quality control and process optimization of this type of product, serving as a positive reference for further study on pentaerythritol fatty acid esters.

Characterization and analysis of non-ionic surfactants by supercritical fluid chromatography combined with ion mobility spectrometry-mass spectrometry.

Comprehensive separation and analysis of non-ionic surfactants have been conducted by coupling supercritical fluid chromatography (SFC) with ion mobility spectrometry-mass spectrometry (IMS-MS). Representative non-ionic surfactants were investigated, including alkylphenol ethoxylates (APEOs), e.g., octylphenol ethoxylates (OPEOs) and fatty alcohol ethoxylates (FAEs), e.g., lauryl alcohol ethoxylates (LAEs). A sub-2-µm high-density diol column was used for chromatographic separation by the first-dimensional SFC due to the differences in ethoxy chain prior to electrospray ionization (ESI). Maintaining the fidelity of pre-ionization separation in the first dimension, the introduction of IMS provided additional post-ionization resolution by broadly fractionating the oligometric ethoxymers based on their size and electric charge within 13.78 ms. Distinguishable series of singly and multiply charged non-ionic species could be clearly observed. The millisecond timescale ion mobility separation perfectly fits the elution time of a chromatographic peak, while effectively feeding components into the fast-scanning time-of-flight (TOF) mass analyzer for characterization and analysis. The orthogonality of the developed separation and analysis system was evaluated, revealing a correlation coefficient and peak spreading angle of 0.2729 and 74.16° for the studied OPEOs and 0.1962 and 78.69° for LAEs. Significant enhancement in peak capacity was achieved for the developed SFC-IMS-MS system with the actual peak capacity measured to be approximately 41 and 160 times higher than that of the dimensions of SFC and IMS, respectively, when used alone. Graphical abstract.

Occurrence, Seasonal Variation and Risk Assessment of Antibiotics in the Surface Water of North China.

In this study, the occurrence, seasonal, and spatial variations of four classes antibiotics were investigated in the surface water of North China. Water samples were taken from 24 sampling sites along rivers in May and August and antibiotics in water samples were detected by SPE-UPLC-MS/MS. The occurrence of all antibiotics except for FLO in May were higher than in August. The mean concentrations of four classes antibiotics detected in May and August were in the following order respectively: quinolones (421.23 ng/L) > tetracyclines (28.37 ng/L) > amphenicols (20.38 ng/L) > sulfonamides (5.79 ng/L) and amphenicols (284.36 ng/L) > quinolones (15.74 ng/L) > tetracyclines (3.05 ng/L) > sulfonamides (0.20 ng/L). The results showed that quinolones and amphenicols were dominant antibiotics among four classes antibiotics. To explore the source of antibiotics from the fish ponds nearby, antibiotic concentration data, which was investigated in the sediment, fish feed and fish revealed a direct relationship between the main antibiotics and fish farms along the rivers. Risk assessment data indicated enrofloxacin and florfenicol could cause higher safety risks to aquatic organisms compared to other antibiotics.

Toxicity assessment of the extractables from multi-layer coextrusion poly ethylene bags exposed to pH=5 solution containing 4% benzyl alcohol and 0.1 M sodium acetate.

A non-target analysis was developed for the analysis of extractables from multi-layer coextrusion bags exposed to 4% benzyl alcohol solution and 0.1 M sodium acetate at pH = 5 for defined periods (15 day, 45 day and 90 day) according to manufacturer instructions based on the ultra-performance liquid chromatography (UPLC) quadrupole-time of flight mass spectrometry (Q-TOF MS). In order to confirm the extractables, principal component analysis (PCA) was used to indicate the differences among samples of different periods. Then, the extractables were identified based on searching the self-built library or online searching. The total content of extractables of 90 day samples was 589.78 µg/L, and the content was in the range of acceptable levels for pharmaceutical manufacturers. The risk assessment of the extractables were evaluated by Toxtree and T.E.S.T. software to avoid the animals bioexperiment.

Detection and Identification of Leachables in Vaccine from Plastic Packaging Materials Using UPLC-QTOF MS with Self-Built Polymer Additives Library.

The direct contact of plastic parts with the medical products raises the possibility that plastic-related contaminants (leachables) may be present in the finished medical product. The leachable components from plastic materials may impact the safety and efficacy of the final medical product, so identification and determination of the leachables are essential for the safety assessment of medical products. A method to identify main leachables-polymer additives in medical products was developed by ultraperformance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF MS) and a self-built library. The library contains 174 additives and the information on their names, formulas, structures, retention times, fragments, classifications, origin, and corresponding MS(E) and MSMS spectra. The reliability of the construction process of the library was guaranteed by the system stability and suitability test. Identification parameters of library application, such as mass error, retention times, fragments, and isotope pattern, were evaluated. Leachables in real vaccine and the intermediates were identified using automatic library searching. In vaccine, the peak m/z 239.0887 that could not be assigned by the library was identified as dimethyl 2-hydroxy-1,3-cyclohexanedicarboxylate using a series of elucidation tools. As a result, the concentrations of leachables in vaccine and the intermediates ranged from 0.85 to 21.91 µg/L.

Simultaneous determination of 16 polycyclic aromatic hydrocarbons in reclaimed water using solid-phase extraction followed by ultra-performance convergence chromatography with photodiode array detection.

A new fast and effective analysis method has been developed to simultaneously determine 16 polycyclic aromatic hydrocarbons in reclaimed water samples by ultra-performance convergence chromatography with photodiode array detection and solid-phase extraction. The parameters of ultra-performance convergence chromatography on the separation behaviors and the crucial condition of solid-phase extraction were investigated systematically. Under optimal conditions, the 16 polycyclic aromatic hydrocarbons could be separated within 4 min. The limits of detection and quantification were in the range of 0.4-4 and 1-10 µg/L in water, respectively. This approach has been applied to a real industrial wastewater treatment plant successfully. The results showed that polycyclic aromatic hydrocarbons were dramatically decreased after chemical treatment procedure, and the oxidation procedure was effective to remove trace polycyclic aromatic hydrocarbons.

[Total dietary exposure assessment of emerging brominated flame retardants in Beijing].

OBJECTIVE: To estimate the exposure characteristic of six emerging brominated flame retardant for Beijing residents by dietary intake. METHODS: 2,3,5,6-tetrabromo-p-xylene (pTBX), pentabromotoluene (PBT), 1, 2, 3, 4, 5-pentabromo-6- ethylbenzene (PBEB), hexahromobenzene (HBB), hexachlorocyclopentadienyl- dibromocyclooctane (DBHCTD) and 1,2-bis(2 ,4 ,6-tribromo phenoxy) ethane (BTBPE) were detected by atmospheric pressure gas chromatography tandem mass spectrometry (APGC-MS/MS) in total dietary samples from Beijing. Dietary intake assessments of human exposure were carried out according to results of determination. RESULTS: PBT, PBEB, HBB and BTBPE were occurred with concentration between 1.2-29.4 pg/g wet weight. The detection rates of HBB and BTBPE in animal--origin samples were higher than those in plant-origin samples, and there were significant differences (P < 0.05). The exposure level of Beijing residents to six emerging brominated flame retardants were 296.8 pg/(kg-d). CONCLUSION: The exposure level of emerging brominated flame retardants by dietary intake in Beijing is relatively low, and meat is the main source of BTBPE dietary intake.

[Lipid metabolomics in serum of hyperuricemic rats induced by fructose based on UPC²-Q/TOF-MS].

To explore the differences in lipid metabolites in serum of hyperuricemic rats induced by fructose and normal rats by using lipid metabolomics technology, and screen the potential biomarkers related to hyperuricemia. The metabolic fingerprint spectrum of the serum in hyperuricemic rats(model group) and normal rats(control group) was obtained and analyzed by using ultra performance convergence chromatography-tandem-Q-time of flight mass spectrometry(UPC ² -Q/TOF-MS) method and the differences of metabolic spectra between two groups were compared via the multivariate statistical methods to screen differential metabolites. The results indicated that there was significant difference in metabolic spectra between model group and control group, and 11 differential metabolites were screened. Then eight potential biomarkers such as arachidonic acid, palmitic acid, oleic acid and linoleic acid were tentatively identified by using the exact mass number and secondary mass spectrometry(MS/MS spectrum). Therefore, a new research method for lipid metabolomics in serum of hyperuricemic rats induced by fructose was established successfully based on UPC ² -Q/TOF-MS. What's more, it was speculated that the abnormal metabolism of fatty acid might be associated with the pathogenesis of hyperuricemia, which would provide scientific basis for early detection and prevention of hyperuricemia.

Rapid identification of polymer additives by atmospheric solid analysis probe with quadrupole time-of-flight mass spectrometry.

RATIONALE: A method using an atmospheric solid analysis probe (ASAP) combined with quadrupole time-of-flight mass spectrometry (QTOFMS) assisted by a pre-built MS library was found to be efficient in fast and direct analysis of additives for polymers. By this method, sample pretreatment could be eliminated from the additives identification process. METHODS: Some crucial parameters, such as desolvation gas temperature, corona current, sample cone voltage and collision energy, should be optimized. A MS library of 100 polymer additives, including phenols (Irganox 1010, Irganox 1076), hydroxyl phenyl benzotriazole derivatives (Tinuvin 326, Tinuvin 327, Tinuvin 328), hindered amines (Tinuvin 944, Tinuvin 770) and plasticizers, was built based on the optimized conditions. To verify the application of the MS library, the ASAP-QTOFMS method was applied to identify complex additives, a simulated polypropylene (PP) sample and a real polymethylmethacrylate (PMMA) sample purchased from a local market. RESULTS: By searching the exact mass, and comparing the MS and MS/MS spectra of samples with standards in the MS library, complex additives such as Irganox GX 2921, as well as additives in PP and PMMA samples, could be identified quickly and easily. The determination of mass accuracy increased the confidence of peak identification as well. Moreover, the results also provided information of the characterization for PP and PMMA polymers. CONCLUSIONS: A rapid identification method has been developed for polymer additives by ASAP-QTOFMS. A MS library of 100 polymer additives was built by this method. Using ASAP-QTOFMS assisted by the pre-built MS library, polymer additives can be quickly identified. This method was found to be a promising tool in the rapid analysis of additives in polymers and polymer matrices.

Catalytic bubble-free hydrogenation reduction of azo dye by porous membranes loaded with palladium nanoparticles.

Catalytic bubble-free hydrogenation reduction of azo dye by porous membranes loaded with palladium (Pd) nanoparticles was studied for the first time. The effects of Pd loading, dye concentration and reuse repetitions of membranes were investigated. In reduction, the dye concentration decreased whereas the pH rose gradually. An optimal Pd loading was found. The catalytic membranes were able to be reused more than 3 times.

Development and validation of an LC-MS/MS method for quantifying NAD+ and related metabolites in mice sciatic nerves and its application to a nerve injury animal model.

Recent studies highlight the pivotal roles of Nicotinamide adenine dinucleotide (NAD+) and its metabolites in aging and neurodegeneration. Accurate quantification of NAD+ and its metabolite levels in cells or tissues is crucial for advancing biochemical research and interventions targeting aging and neurodegenerative diseases. This study presents an accurate, precise, and rapid LC-MS/MS method using a surrogate matrix to quantify endogenous substances NAD+, nicotinamide mononucleotide (NMN), nicotinamide (NAM), adenosine diphosphate ribose (ADPR), and cyclic adenosine diphosphate ribose (cADPR) concentrations in mice sciatic nerves. Considering the properties of the phosphate groups in the analytes, the column and mobile phase were systematically optimized. These five polar analytes exhibited excellent analytical performance and baseline separation within 5 min on an Atlantis Premier BEH C18 AX column, with methylene phosphonic acid as a mobile phase additive. Enhanced sensitivity addressed the challenges posed by the small sample size of mice sciatic nerve and low NMN and cADPR detection. The method was fully validated, with linear correlation coefficients exceeding 0.992, precision (%relative standard deviation, RSD) values within 8.8%, and accuracy values between 92.2% and 107.3%, suggesting good reproducibility. Analytical recoveries in spiked and diluted matrix ranged from 87.8% to 104.7%, indicating the suitability of water as a surrogate matrix. Application of the method to quantify NAD+ and its metabolite levels in normal and injured mice sciatic nerve identified cADPR as a sensitive biomarker in the nerve injury model. This method is anticipated to deepen our understanding of the connections between NAD+ and its metabolites in health and disease, potentially improving diagnoses of various neurological disorders and aiding drug development for aging and neurodegenerative diseases.

Anti-bacterial films developed by incorporating shikonin extracted from radix lithospermi and nano-ZnO into chitosan/polyvinyl alcohol for visual monitoring of shrimp freshness.

In recent years, the utilization of smart colorimetric packaging films for monitoring food freshness has garnered significant concentration. However, their limited tensile strength, hydrophobicity, antioxidant, and antibacterial properties have been substantial barriers to widespread adoption. In this study, we harnessed the potential of biodegradable materials, specifically chitosan/polyvinyl alcohol, alongside shikonin extracted from Radix Lithospermi and ZnO nanoparticles, to create a novel colorimetric sensing film. This film boasts an impressive tensile strength of 82.36 ± 2.13 MPa, enhanced hydrophobic characteristics (exemplified by a final contact angle of 99.81°), and outstanding antioxidant and antibacterial properties. It is designed for real-time monitoring of shrimp freshness. Additionally, we verified the effectiveness of this sensing film in detecting shrimp freshness across varying temperature conditions, namely 25 °C and 4 °C was validated through the measurement of total volatile basic nitrogen (TVB-N). Visual inspection unequivocally revealed a transition in color from dark red to purple-light blue and finally to dark bluish providing a clear indication of shrimp spoilage, which demonstrated a strong correlation with the TVB-N content in shrimp measured through standard laboratory procedures. The colorimetric sensing film developed in this study holds great promise for creating smart labels with exceptional antioxidant and antibacterial properties, tailored for visual freshness monitoring of shrimp.

Accurate prediction of Kp,uu,brain based on experimental measurement of Kp,brain and computed physicochemical properties of candidate compounds in CNS drug discovery.

A mathematical equation model was developed by building the relationship between the fu,b/fu,p ratio and the computed physicochemical properties of candidate compounds, thereby predicting Kp,uu,brain based on a single experimentally measured Kp,brain value. A total of 256 compounds and 36 marketed published drugs including acidic, basic, neutral, zwitterionic, CNS-penetrant, and non-CNS penetrant compounds with diverse structures and physicochemical properties were involved in this study. A strong correlation was demonstrated between the fu,b/fu,p ratio and physicochemical parameters (CLogP and ionized fraction). The model showed good performance in both internal and external validations. The percentages of compounds with Kp,uu,brain predictions within 2-fold variability were 80.0 %-83.3 %, and more than 90 % were within a 3-fold variability. Meanwhile, "black box" QSAR models constructed by machine learning approaches for predicting fu,b/fu,p ratio based on the chemical descriptors are also presented, and the ANN model displayed the highest accuracy with an RMSE value of 0.27 and 86.7 % of the test set drugs fell within a 2-fold window of linear regression. These models demonstrated strong predictive power and could be helpful tools for evaluating the Kp,uu,brain by a single measurement parameter of Kp,brain during lead optimization for CNS penetration evaluation and ranking CNS drug candidate molecules in the early stages of CNS drug discovery.

Smart colorimetric indicator films prepared from chitosan and polyvinyl alcohol with high mechanical strength and hydrophobic properties for monitoring shrimp freshness.

This work aimed to develop and characterize a colorimetric indicator films based on chitosan (CS), polyvinyl alcohol (PVA), and shikonin (SKN) from radix Lithospermi by casting method. The prepared films can serve as smart packaging for monitoring shrimp freshness which having excellent antimicrobial and antioxidant activity. The shikonin containing films have better hydrophobicity, barrier properties, and tensile strength. The release kinetics analysis shows that the loading amount causes a prolonged release of SKN from the prepared films. Increasing SKN in the CS/PVA film from 1 wt% to 2 wt% improved antibacterial effect for 24 h. Additionally, pH-sensitive color shifts from reddish (pH 2) to purple-bluish (pH 13) were visually seen in shikonin based solutions as well as films. The CS/PVA/SKN film detected shrimp deterioration at three temperatures (25, -20, and 4 °C) through color change. This study introduces a favorable approach for smart packaging in the food industry using multifunctional films.

Determination of multi-residue pesticides in dairy products using single-step emulsification/demulsification clean-up strategy combined with low-pressure gas chromatography-tandem mass spectrometry.

In this study, a simple, sensitive, and rapid method was developed for the simultaneous determination of 99 kinds of pesticides in fatty milk samples. This novel emulsification-demulsification clean-up approach, coupled with an automatic demulsification-dehydration cartridge, allowed rapid single-step clean-up operation and high throughput. It also achieved effective and selective removal of lipids. The analysis was performed using low-pressure gas chromatography-tandem mass spectrometry (LPGC-MS/MS). Based on the optimal conditions, the targeted pesticides showed good linearity in the range of 5-250 µg/kg, with recoveries of 70-120% at spiking levels of 5, 10, and 20 µg/kg in cow milk, goat milk, and almond milk, respectively. The limit of quantification for most pesticides was 5 µg/kg, and the RSDs were lower than 20%. Analysis of real dairy products obtained from local markets revealed a potential risk in plant-derived almond milk, but no significant risks were found for cow and goat milk.

VOC data-driven evaluation of vehicle cabin odor: from ANN to CNN-BiLSTM.

Emissions of volatile organic compounds (VOCs) in vehicles represent a significant problem, causing unpleasant odors. To mitigate VOCs and odors in vehicles, it is critical to choose interior parts with low odor and VOC emissions. However, prevailing odor evaluation methods are subjective, costly, and potentially harmful to the health of evaluators. In this study, we analyzed 139 automotive interior parts and 92 vehicles, establishing a cost-effective, data-driven method for odor evaluation. The contents of benzene, toluene, ethylbenzene, xylene, styrene, formaldehyde, acetaldehyde, acrolein, and total volatile organic compounds (TVOC) were detected by thermal desorption gas chromatography-mass spectrometry (TD-GC/MS) and high-performance liquid chromatography with an ultraviolet detector (HPLC-UV). Professional odor evaluators assessed the odors, identifying intensity levels from 2.0 to 4.5 in interior parts and 2.5 to 3.5 in whole vehicles. Leveraging this data, we applied four supervised learning algorithms to develop predictive models for the odor intensity of both interior parts and entire vehicles. During model training, we implemented early stopping techniques for the artificial neural network (ANN) and convolutional neural network-bidirectional long short-term memory (CNN-BiLSTM) models, while optimizing the support vector machine (SVM) and extreme gradient boosting (XGBoost) models using the GridSearch algorithm. The evaluation results reveal that the CNN-BiLSTM model performs the best, achieving an average accuracy of 89% for unknown samples within an odor intensity level of 0.5. The root mean square error (RMSE) is 0.24, and the mean absolute error (MAE) is 0.08. The model also underwent a sevenfold cross-validation, achieving an accuracy of 83.43%. Additionally, we employed SHapley Additive exPlanations (SHAP) for the interpretative analysis of the model, which confirmed the consistency of each VOC's odor contribution with human olfactory rules. By predicting odors based on VOCs through supervised learning, this study reduces the costs and enhances the efficiency and applicability of odor assessment across various vehicle interiors.

A LC-MS/MS method for the simultaneous quantitative determination of aldosterone, its precursor 18-hydroxycorticosterone and its metabolite tetrahydroaldosterone in human urine.

Aldosterone (ALD), its precursor 18-hydroxycorticosterone (18-OHB) and its metabolite tetrahydroaldosterone (TH-ALD) are important biomarkers for the diagnosis of primary aldosteronism (PA). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is increasingly utilized in the detection of small molecules of hormones because it has advantages in terms of specificity and sensitivity. The objective of this study is to develop a new LC-MS/MS method for the simultaneous quantification of ALD (free), 18-OHB, and TH-ALD in human urine and attempt to diagnose primary aldosteronism using different indicators. The urine samples were treated with a solid-phase extraction pretreatment technique and the three analytes were separated on a reversed-phase column and detected on a triple quadrupole mass spectrometer. The established method was validated according to CLSI C62-A standard guidelines. The calibration ranges from 25 pg/mL to 5000 pg/mL for aldosterone (free), 18-hydroxycorticosterone and tetrahydroaldosterone, and the lower limit of quantification for these three analytes was 25 pg/mL. The matrix effects and recoveries of these three analytes ranged from 85.1 % to 115 % and from 86.3 % to 114 %, respectively. The intra-day and inter-day precision ranged from 1.29 % to 6.78 % and from 1.77 % to 8.64 %, respectively. The performance of the method met the requirements of the guidelines. 40 clinical urine samples including 22 PA patients and 18 non-PA patients were detected, and the ROC curves of three diagnostic indicators were established. The area under the curve (AUC) of ALD (free) is the biggest, so ALD (free) was the best compound to be used as a diagnostic indicator in this study. When the cut-off point was taken as 141 ng/24-h, the sensitivity was 72.7 % and the specificity was 88.9 %. We developed and validated an LC-MS/MS method for the simultaneous quantification of ALD (free), 18-OHB and TH-ALD in human urine. Our study provides a reference for the use of new biomarkers for the diagnosis of primary aldosteronism.

Effect of ammonium on liquid- and gas-phase protonation and deprotonation in electrospray ionization mass spectrometry.

The electrospray ionization (ESI) is a complex process and there has been a long debate regarding the gas-phase effect on ion generation in the process. In this paper we investigated the effect of liquid chromatographic mobile phase additives (formic acid, aqueous ammonia and their combination) on the ESI signal intensities for a wide variety of compounds. The addition of a trace amount of aqueous ammonia to the common formic acid-methanol mobile phase significantly enhances the ESI signals of protonated molecules and suppresses the formation of sodium adduct ions. This effect is well observed for the compounds containing the -N-C=O group but not for those without N or O atoms. The ESI signal intensity of deprotonated molecules increases with increase in pH of the mobile phase for neutral compounds, such as substituted urea, whereas this trend is not observed for acidic compounds such as phenoxy acids. The mechanistic analysis regarding liquid- and gas-phase protonation and deprotonation is discussed.