A rapid and sensitive analytical methodology for the simultaneous biomonitoring of two direct oral anticoagulant drugs and their major metabolites in thromboembolic disordered patients samples for clinical evaluations.

Apixaban and dabigatran are the two major direct oral anticoagulant drugs to treat thromboembolic disordered patients. Increasing the clinical application for the thromboembolic disorder and monitoring the concentrations of apixaban, dabigatran, and their metabolites are essential in most clinical circumstances. In this work, we developed a rapid analytical methodology comprising of vortex-assisted salt-enhanced liquid-liquid microextraction technique coupled with UHPLC-MS/MS for the extraction and simultaneous determination of two major direct oral anticoagulant drugs (apixaban, dabigatran), and their two major metabolites from plasma, serum, and urine samples of patients. The developed method was optimized with various procedural steps and validated to study the analytical merits. The developed method yielded a good detection limit of 0.01 ∼ 0.37 ng/mL, 0.01 ∼ 0.32 ng/ml, and 0.01 ∼ 0.27 ng/mL for four target analytes in the plasma, serum, and urine matrices. Moreover, extraction recoveries ranged from 85.11 - 113.57% (for plasma), 89.63 - 110.47% (for serum), and 87.44 -106.79% (for urine samples) with 8.78% RSD. In addition, the method exhibited good R2 values of 0.999 for all four target analytes, and the specificity and carryover study revealed no carryover effect from the UHPLC-MS/MS system for determining the apixaban, dabigatran, and their metabolites. Due to the above advantages, the developed analytical technique was applied to examine 11 real-time clinical patients' samples, and the observed results were satisfactory for all three different sample matrices. Therefore, this analytical method can be applied for biomonitoring apixaban, dabigatran, and their two major metabolites with high sensitivity in a short time for various clinical applications.

Exposure and risk assessment of urinary trans, trans-Muconic acid in school-age children in the vicinity of a petrochemical complex in Central Taiwan.

School-age children living near large petrochemical factories may be at high risk of exposure to benzene released during manufacturing processes. We aimed to investigate the urinary concentrations of trans, trans-muconic acid (t,t-MA) in school-age children living near a petrochemical complex and to estimate their cumulative risk of benzene exposure. We examined an established cohort (Taiwan Petrochemical Complex Cohort for Children, TPE3C) of school-age children (aged 6-13 years) who lived near large petrochemical factories in central Taiwan between October 2013 and September 2014. The cohort comprised 297 children from five elementary schools, namely S.-C. Branch (n = 63, school A, ~0.9 km), F.-A. (n = 51, school B, ~2.7 km), C.-T. (n = 63, school C, ~5.5 km), M.-L. (n = 54, school D, ~6.9 km), and L.-F. (n = 66, school E, ~8.6 km). We analyzed the urinary t,t-MA levels of each participant and estimated their daily intake of benzene. We also performed multiple regression analysis to investigate potential risk factors for a high urinary t,t-MA level in the study cohort. The median urinary t,t-MA levels and median estimated benzene daily intake of the children from each school were as follows: school A, 64.07 ng/mL, 11.13 µg/kg/day; school B, 61.01 ng/mL, 15.32 µg/kg/day; school C, 59.38 ng/mL, 14.81 µg/kg/day; school D, 42.35 ng/mL, 11.67 µg/kg/day; school E, undetected, 0.14 µg/kg/day. The distance between a school and a petrochemical complex (greater distance: ß = -0.26, 95% confidence interval [CI] = -0.52 to 0.00, p = 0.053), and the age of the children (older age: ß = -3.44, 95% CI = -5.90 to -1.46, p < 0.001) were identified as potential risk factors. After confounders were adjusted for, the creatinine adjusted urinary t,t-MA levels of the school-age children tended to be lower when the distance between their school and a petrochemical complex was greater.

Rapid identification and monitoring of cooking oil fume-based toxic volatile organic aldehydes in lung tissue for predicting exposure level and cancer risks.

Cooking oil fumes (COFs) comprised of a mixture of cancer-causing volatile organic aldehydes (VOAs), particularly trans, trans-2,4-decadienal (t,t-DDE), 4-hydroxy-hexenal (4-HHE), and 4-hydroxy-nonenal (4-HNE). Monitoring toxic VOAs levels in people exposed to different cooking conditions is vital to predicting the cancer risk. For this purpose, we developed a fast tissue extraction (FaTEx) technique combined with UHPLC-MS/MS to monitor three toxic VOAs in mice lung tissue samples. FaTEx pre-treatment protocol was developed by combining two syringes for extraction and clean-up process. The various procedural steps affecting the FaTEx sample pre-treatment process were optimized to enhance the target VOAs' extraction efficiency from the sample matrix. Under the optimal experimental conditions, results exhibit good correlation coefficient values > 0.99, detection limits were between 0.5-3 ng/g, quantification limits were between 1-10 ng/g, and the matrix effect was <18.1%. Furthermore, the extraction recovery values of the spiked tissue exhibited between 88.9-109.6% with <8.6% of RSD. Cooking oil fume (containing t,t-DDE) treated mice at various time durations were sacrificed to validate the developed technique, and it was found that t,t-DDE concentrations were from 14.8 to 33.8 µg/g. The obtained results were found to be a fast, reliable, and semi-automated sample pre-treatment technique with good extraction efficiency, trace level detection limit, and less matrix effect. Therefore, this method can be applied as a potential analytical method to determine the VOAs in humans exposed to long-term cooking oil fumes.

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

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

Simultaneous biomonitoring of volatile organic compounds' metabolites in human urine samples using a novel in-syringe based fast urinary metabolites extraction (FaUMEx) technique coupled with UHPLC-MS/MS analysis.

Assessing the impact of human exposure to environmental toxicants is often crucial to biomonitoring the exposed dose. In this work, we report a novel fast urinary metabolites extraction (FaUMEx) technique coupled with UHPLC-MS/MS analysis for the highly sensitive and simultaneous biomonitoring of the five major urinary metabolites (thiodiglycolic acid, s-phenylmercapturic acid, t,t-muconic acid, mandelic acid, and phenyl glyoxylic acid) of common volatile organic compounds' (VOCs) exposure (vinyl chloride, benzene, styrene, and ethylbenzene) in human. FaUMEx technique comprises of two-steps, liquid-liquid microextraction was performed first in an extraction syringe using 1 mL of methanol (pH 3) as an extraction solvent and then, the extractant was passed through a clean-up syringe (pre-packed-with various sorbents including 500 mg anhydrous MgSO4, 50 mg C18, and 50 mg SiO2) to obtain the high order of matrice clean-up and preconcentration efficiency. The developed method displayed excellent linearity, and the correlation coefficients were >0.998 for all the target metabolites with detection and quantification limits of 0.02-0.24 ng mL-1 and 0.05-0.72 ng mL-1, respectively. Furthermore, the matrix effects were < ±5%, and inter and intra-day precision were <9%. Moreover, the presented method was applied and validated to real sample analysis for biomonitoring of VOC's exposure levels. The results showed that the developed FaUMEx-UHPLC-MS/MS method is fast, simple, low-cost, low-solvent consumption, high sensitivity with good accuracy and precision for five targeted urinary VOCs' metabolites. Therefore, the presented dual-syringe mode FaUMEx strategy with UHPLC-MS/MS technique can be applied to biomonitoring of various urinary metabolites to assess human exposure to environmental toxicants.

Ultra-sensitive determination of Ochratoxin A in coffee and tea samples using a novel semi-automated in-syringe based coagulant-assisted fast mycotoxin extraction (FaMEx) technique coupled with UHPLC-MS/MS.

In this study, we demonstrated a novel semi-automated in-syringe-based coagulant-assisted liquid-liquid microextraction (IS-CGA-LLME) as fast mycotoxin extraction (FaMEx) technique coupled with ultra-high-performance liquid chromatography connected with a tandem-mass spectrometer (UHPLC-MS/MS) for the quantification of mycotoxin (Ochratoxin A, OT-A) in coffee and tea samples. IS-CGA-LLME is a three-step extraction process that includes extraction of OT-A from sample matrix using low-volume solvent extraction, then the extractant was cleaned-up using a coagulation process, and finally, the decolorized/matrix removed sample solution was processed for LLME for target analyte's pre-concentration. The final extractant was analyzed using UHPLC-MS/MS for OT-A quantification. Under the optimized experimental conditions, highly sensitive detection and quantification limits were obtained at 0.001 and 0.003 ng g-1 for OT-A with excellent extraction recovery (93-111%) and precision <10%. These results proved that the developed method is a simple, highly sensitive, semi-automated, low-matrix effect and efficient procedure for the determination of mycotoxins in food samples.

Eco-friendly fabrication of nonenzymatic electrochemical sensor based on cobalt/polymelamine/nitrogen-doped graphitic-porous carbon nanohybrid material for glucose monitoring in human blood.

The design and development of eco-friendly fabrication of cost-effective electrochemical nonenzymatic biosensors with enhanced sensitivity and selectivity are one of the emerging area in nanomaterial and analytical chemistry. In this aspect, we developed a facile fabrication of tertiary nanocomposite material based on cobalt and polymelamine/nitrogen-doped graphitic porous carbon nanohybrid composite (Co-PM-NDGPC/SPE) for the application as a nonenzymatic electrochemical sensor to quantify glucose in human blood samples. Co-PM-NDGPC/SPE nanocomposite electrode fabrication was achieved using a single-step electrodeposition method under cyclic voltammetry (CV) technique under 1 M NH4Cl solution at 20 constitutive CV cycles (sweep rate 20 mV/s). Notably, the fabricated nonenzymatic electroactive nanocomposite material exhibited excellent electrocatalytic sensing towards the quantification of glucose in 0.1 M NaOH over a wide concentration range from 0.03 to 1.071 mM with a sensitive limit of detection 7.8 µM. Moreover, the Co-PM-NDGPC nanocomposite electrode with low charge transfer resistance (Rct∼81 Ω) and high ionic diffusion indicates excellent stability, reproducibility, and high sensitivity. The fabricated nanocomposite materials exhibit a commendable sensing response toward glucose molecules present in the blood serum samples recommends its usage in real-time applications.

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

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

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

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

Variation in Polycyclic Aromatic Hydrocarbon Contamination Between Native and Introduced Species of Fishes of Pallikaranai Wetland, Chennai, Tamil Nadu, India.

The impacts of invasive fish species on recipient communities are mostly considered a threat to the biodiversity of freshwater systems. A characteristic of introduced species turning invasive is their higher tolerance to environmental stressors. To understand if non-native fishes in Pallikaranai wetland, Tamil Nadu, India, are more tolerant to anthropogenic pressures in the Wetland, we assessed the variation in Polycyclic Aromatic Hydrocarbon contamination between introduced and native fish species. Mean levels of Naphthalene, fluorene, phenanthrene, anthracene, pyrene, and total PAH in samples of introduced species were higher than native species, while High Molecular weight PAH and carcinogenic PAH4 were higher in native fish species. The data was also analysed to assess if co-variates (organs, seasons, and sex) affected PAH accumulation patterns in non-native species. It was observed that only organs, sex, and year contributed significantly.