Gas Chromatography-high Resolution Mass Spectrometry Research Articles

Deciphering Isotopic Fine Structures of Silylated Compounds in Gas Chromatography-Vacuum Photoionization Orbitrap Mass Spectrometry of Bio-Oils.

We introduce vacuum resonance-enhanced multiphoton ionization (REMPI) with high-resolution Orbitrap Fourier transform mass spectrometry (FTMS) for analyzing silylated polar compounds. UV laser radiation at 248 nm sensitively and selectively targets aromatic constituents, while high-resolution mass spectrometry (HRMS) enables high-performance mass spectrometric detection. This workflow enhances the detection confidence of polar constituents by identifying unique isotopologue patterns, including at the isotopic fine structure (IFS) level, in analytical standards and complex bio-oils. A direct and derivatized gas chromatography (GC) procedure on a polar standard component mixture allowed us to explore the general ionization and detection characteristics of REMPI FTMS. HRMS enabled the examination of the complex isotopologue profiles, revealing distinct patterns for the CHOxSiy-class compounds. Particularly in complex mixtures, this isobaric/isonucleonic complexity exceeded the classical mass resolution capabilities of the employed Orbitrap D30 series and prompted the usage of prolonged transients via an external data acquisition system. This procedure substantially improved mass spectrometric results by recording the unreduced time-domain transient data for up to 2 s. Notably, the ability to distinguish diagnostic isotopic pairs, such as 12C/29Si vs 13C/28Si with a mass split of ∼3.79 mDa and 13C12C/28Si29Si vs 13C2/28Si2, with an approximate mass difference of ∼3.32 mDa, demonstrates a significant and expected performance improvement. Finally, we benchmark the GC HRMS methodology to identify silylated oxygenated and nitrogen-containing constituents in ultracomplex bio-oil samples. The presented approach of utilizing the silicon isotope pattern and unique isotopologue mass splits for increasing attribution confidence can be applied beyond bio-oils toward the general GC analyses of polar oxygenates.

Liquid crystal monomers in human, dog and cat feces from the United States

Little is known about exposure of humans and companion animals to liquid crystal monomers (LCMs), which are extensively used in digital displays. We determined the concentrations of 52 LCMs in feces of humans, pet dogs and cats from New York State, USA, using gas chromatography-high resolution mass spectrometry (GC-HRMS). Twenty-four, eight, and six LCMs, that were mainly fluorinated, were detected in human, dog, and cat feces, respectively. ∑LCMs concentrations in the feces of humans (mean: 8.01 ng/g dry weight [dw]) were significantly higher (p < 0.05) than those of dogs (mean: 1.82 ng/g dw) and cats (mean: 1.24 ng/g dw) and with concentrations measured as high as 39.8 ng/g dw. Rel-4′-((1r,1′r,4 R,4′R)−4′-ethyl-[1,1′-bi(cyclohexan)]−4-yl)−3,4-difluoro-1,1′-biphenyl (RELEEBCH or 2bcHdFB) was found at the highest detection frequency (DF) among LCMs analyzed in human (DF: 89 %), dog (DF: 28 %), and cat (DF: 50 %) feces, although this compound accounted only < 4 % of ∑LCM concentrations. The mean cumulative daily intakes of ∑LCMs, calculated through a reverse dosimetry approach, were 71.7, 87.5, and 10.7 ng/kg body weight (bw)/day for humans, dogs, and cats, respectively. This study provides evidence of exposure of both humans and pets to LCMs, highlighting the importance of assessing sources of exposure and associated health risks.

Analysis of brominated flame retardants exposure-associated chronic kidney disease risk in the US population from the NHANES

BackgroundExposure to brominated flame retardants (BFRs) may contribute the advancement of chronic kidney disease (CKD). The objective is to evaluate the renal effects of BFRs in patients with CKD. MethodsTotally 7235 US participants of whom 1187 (16.41 %) were diagnosed with CKD were screened for this investigation from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016. The isotope dilution gas chromatography high-resolution mass spectrometry (GC/IDHRMS) was employed for identification of 11 polybrominated diphenyl ethers (PBDEs) and PBB153 serving as the exposure factor. A set of covariates concerning basic characteristics, renal function indicators and suffering from diseases of these participants was considered as potential confounding factors. Subgroup analyses to examine the impact of age and gender on the relationship between serum BFRs and CKD, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN). Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analyses were applied to identify relationship of individual BFRs and other anthropometric indicators in CKD. ResultsAfter adjusting for available confounding factors, PBDE100, PBDE28, PBDE85, PBDE47, PBDE99, and PBDE154 were positively correlated with CKD. PBDE28, PBDE66, PBDE47, PBDE183, PBDE100, PBDE99, PBDE85, PBDE154, and PBB153 were significantly negatively correlated with eGFR. PBDE66 and PBDE183 were positively correlated with UACR. PBDE28, PBDE17, PBDE66, PBDE100, PBDE47, PBDE85, PBDE154, PBDE99, PBDE183 and PBB153 were positively correlated with Scr. PBDE17, PBDE28, PBDE154, PBDE66, PBDE47, PBDE99, and PBDE209 were negatively associated with BUN. PBB153 was positively correlated with BUN. The subgroup results gender and age are key factors affecting the relationship of PBDEs and renal function indicators. Both WQS and QGS analyses revealed that exposure to mixed BFR was negatively correlated with eGFR and BUN, of which PBB153 and PBDE66 contributed the most, respectively, as well as positively correlated with Scr, in which PBDE66 contributed the most. ConclusionSpecific BFRs exposure was significantly correlated with renal function indicators, enhancing the potential risk of CKD. This pioneer investigation shed light on an overlooked impact of BFR exposure on CKD in US.

Brominated flame retardant in animal feeds from Poland

The safety of food of animal origin is closely related to feed quality. Feed pollution by brominated flame retardants (BFRs) leads to the exposure of animals and consumers of food of animal origin to these substances. The study aimed to assess the concentration of ten PBDE (BDE-28, 47, 49, 99, 100, 138, 153, 154, 183, and 209) congeners and eight nBFRs (TBX, PBT, HBB, PBEB, EH-TBB, BTBPE, BEH-TBPH, and DBDPE) in 59 feed and feed materials from six different feed categories (277/2012/EU). The quantification of analytes was based on isotopic dilution and gas chromatography–high-resolution mass spectrometry (GC-HRMS). All 59 feed samples were contaminated with at least one of the analytes. PBDEs and nBFRs were found in 78% and 91% of the samples, respectively. BFR content ranged from 0.18 to 5.87 μg·kg-1 in feed with a 12% moisture content, and the most contaminated category was vegetable oils, followed by fishmeal, feeds for fish, animal fats, and compound feeds for pigs. The least contaminated samples turned out to be compound feeds for chickens. This study confirms the general trend of decreasing PBDE concentrations in fishmeal. In the investigated samples, BDE-47 and BDE-209 contributed the most to the ∑PBDE content. DBDPE, HBB, and PBT contributed the most to the investigated ∑nBFRs. The widespread occurrence of nBFRs in feed seems disturbing because these compounds have replaced PBDEs. Their concentrations in the feed may most likely exceed those of PBDEs in the coming years.

Chemical Exposomics in Human Plasma by Lipid Removal and Large-Volume Injection Gas Chromatography-High-Resolution Mass Spectrometry.

For comprehensive chemical exposomics in blood, analytical workflows are evolving through advances in sample preparation and instrumental methods. We hypothesized that gas chromatography-high-resolution mass spectrometry (GC-HRMS) workflows could be enhanced by minimizing lipid coextractives, thereby enabling larger injection volumes and lower matrix interference for improved target sensitivity and nontarget molecular discovery. A simple protocol was developed for small plasma volumes (100-200 μL) by using isohexane (H) to extract supernatants of acetonitrile-plasma (A-P). The HA-P method was quantitative for a wide range of hydrophobic multiclass target analytes (i.e., log Kow > 3.0), and the extracts were free of major lipids, thereby enabling robust large-volume injections (LVIs; 25 μL) in long sequences (60-70 h, 70-80 injections) to a GC-Orbitrap HRMS. Without lipid removal, LVI was counterproductive because method sensitivity suffered from the abundant matrix signal, resulting in low ion injection times to the Orbitrap. The median method quantification limit was 0.09 ng/mL (range 0.005-4.83 ng/mL), and good accuracy was shown for a certified reference serum. Applying the method to plasma from a Swedish cohort (n = 32; 100 μL), 51 of 103 target analytes were detected. Simultaneous nontarget analysis resulted in 112 structural annotations (12.8% annotation rate), and Level 1 identification was achieved for 7 of 8 substances in follow-up confirmations. The HA-P method is potentially scalable for application in cohort studies and is also compatible with many liquid-chromatography-based exposomics workflows.

Exploring the pyrolytic degradation of seventeen phthalate esters using the non-targeted regions of interest-multivariate curve resolution (ROIMCR) chemometric method

The global use of phthalate esters (PAEs) in plastic production entails a need for developing effective remediation strategies to minimize exposure and health risks. In this study, pyrolysis degradation processes are evaluated for 17 different PAEs that were analyzed by high-resolution gas chromatography-mass spectrometry (Pyr-GC-Orbitrap-MS) at different temperatures (300 °C, 400 °C, 500 °C, 600 °C, 700 °C, 800 °C) both in electron ionization (EI) and positive chemical ionization (PCI) mode. All the analytical data generated have been processed with the Regions of Interest Multivariate Curve Resolution (ROIMCR) chemometrics method. A preliminary selection of the Mass Spectrometry Regions of Interest (ROIs) coupled to a bilinear factor decomposition method (MCR-ALS) allowed the identification of 4 principal components, which were used to define the thermal degradation process. ROIMCR method is a powerful tool for non-targeted analysis which allows the resolution of the elution and spectral profiles of the different constituents present in the analyzed samples, which were confirmed using PCI. Moreover, ROIMCR was used to resolve and identify the different products generated during the studied degradation processes. As a result, 10 new thermal degradation products were identified in the analysis of the different sample sets. Finally, the degradation efficiencies higher than 99.8 % were obtained for all the PAEs at 800 °C, except for benzoic acid-benzyl ester, whose removal efficiency decreased to 94.8 %. As phthalates are widespread and toxic compounds for the environment and for humans, there is a need for new remediation technologies. This study provides new knowledge to understand their elimination through thermal processes. We combine mass spectrometric data with powerful chemometric processing to determine the removal efficiency, to understand the degradation process and to identify the degradation compounds formed through thermal decomposition.

SPME arrow-based extraction for enhanced targeted and untargeted urinary volatilomics

BackgroundVolatile organic compounds (VOCs) present in human urine are promising biomarkers for various health conditions and environmental exposures. However, their reliable detection is challenging due to the complexity of urinary matrices and the low concentrations of VOCs. Moreover, untargeted approaches present considerable challenges in terms of data interpretation, increasing the complexity of method development. Here we address these challenges by developing a new method that combines solid-phase microextraction (SPME) Arrow with gas chromatography-high resolution mass spectrometry (GC-HRMS), using a design of experiments (DOE) approach for targeted and untargeted compounds. This methodology, specifically tailored for SPME Arrow, represents a significant advancement in untargeted urinary analysis. ResultsThe method was developed based on targeted and untargeted outcomes, were ranking results focus on the highest response area of 11 spiked target VOCs representative of urinary volatilomics, and on identifying the maximum untargeted number of VOCs. The method was developed focusing on the highest response area of 11 spiked target VOCs representative of urinary volatilomics and identifying the maximum number of VOCs. A univariate method determined the optimal coating type, urine volume, and salt addition. Subsequently, a central composite design (CCD) DOE was used to determine ideal temperature, extraction, and incubation times. The best method obtained has an extraction time of 60 min at a temperature of 53 °C, with an SPME Arrow CAR/PDMS using 2 mL of urine, with 0.25 % w/v of NaCl and a pH of 2. Compared to conventional SPME fibers, the SPME Arrow showed improved extraction efficiency, detecting more VOCs. Finally, the enhanced method was successfully applied to urine samples from children exposed and non-exposed to tobacco smoke, identifying specific VOCs, like p-cymene and p-isopropenyl toluene related to tobacco exposure. SignificanceBy integrating both targeted and untargeted approaches, the developed method comprehensively captures the complexity of urinary metabolomics. This dual strategy ensures the precise identification of known compounds and the discovery of novel biomarkers, thereby providing a more complete metabolic profile. Such an approach is crucial for advancing in non-invasive diagnostics and environmental health studies, as it offers deeper insights into the intricate relationships between metabolic processes and various health conditions.

Association between brominated flame retardants (BFRs) and periodontitis: Results from a large population-based study

BackgroundBrominated flame retardants (BFRs) are widely utilized to mitigate the flammability of various materials. Previous studies have revealed the impact of BFRs exposure on hormonal disruption and bone metabolism which are closely related to periodontitis. However, it remains unknown the potential relationship between BFRs and periodontitis. This study aimed to explore the association between BFRs exposure and periodontitis in US adults.MethodsThe data analyzed in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009–2014. Twelve serum BFRs were quantified using isotope dilution gas chromatography high-resolution mass spectrometry. Univariable and multivariable logistic regression was employed to evaluate the association between serum BFRs and periodontitis. Bayesian kernel machine regression (BKMR) analyses were utilized to assess the association between mixtures of BFRs and periodontitis.ResultsA total of 3311 eligible participants were included. Serum BFRs (PBDE-47, PBDE-99, and PBDE-154) were significantly associated with periodontitis, and the odds ratios (ORs) and corresponding 95% confidence intervals(CIs) were 1.15(1.01,1.29), 1.10(1.01,1.20), and 1.12(1.01,1.25), respectively. Notably, these three BFRs were also significantly associated with the severity of periodontitis. Additionally, the BKMR model revealed a significant association between the mixture of all twelve BFRs and periodontitis.ConclusionsThis preliminary study suggests a significant association between specific serum BFRs (PBDE-47, PBDE-99, and PBDE-154) and periodontitis and its severity. Further prospective and experimental studies are warranted to validate our findings.

Analysis of polycyclic aromatic hydrocarbons in Brazilian human milk: A simple and effective approach

Human milk is the best source of nutrition for infants due to its essential biologically active components. However, it can contain potentially harmful chemicals, such as polycyclic aromatic hydrocarbons, originating from contaminated air and food, which can cause adverse effects to infants. Using a Plackett-Burman design, a QuEChERS protocol was optimized to determine 13 polycyclic aromatic hydrocarbons in 79 Brazilian human milk samples by gas chromatography high-resolution mass spectrometry. Limits of quantification below 1 μg/kg were achieved for all compounds, with recoveries ranging between 61 % and 126 %. Six PAHs, including benzo(g,h,i)perylene, dibenzo(a,h)anthracene, fluoranthene, indeno(1,2,3-cd)pyrene, phenanthrene, and pyrene were detected in 40 samples. Mature milk exhibited the highest incidence of PAHs, with approximately 44 % of the positive samples, compared to 27 % for both colostrum and transitional milk. The concentrations detected varied between < LOQ and 1.14 μg/kg, with pyrene being the most frequently found PAH in the human milk samples. The estimated daily intake and margin of exposure of PAHs showed the highest values for babies aged 0–15 days for all PAHs evaluated. Despite the low levels of PAHs found in the analyzed samples, discontinuing breastfeeding is not recommended. This represents the first study on the incidence of PAHs in Brazilian human milk.

Nylon 6 film coated with poly-tetrahydrofuran sol–gel solution in face mask as a non-invasive in vivo sampling device for caffeine in human exhaled breath aerosol

Caffeine is an alkaloid compound that can excite the central nervous system and effectively relieve fatigue in moderation. However, excessive caffeine consumption can block blood vessels, raising blood pressure and increasing the risk of atherosclerosis. The International Agency for Research on Cancer of the World Health Organization has listed caffeine in category 3 carcinogens, so it is crucial that caffeine be detected easily and accurately. Exhaled breath aerosol (EBA), which consists of a large number of volatile substances and complex biological matrices, can not only reflect the physiological state of the human body, ingested substances, and environmental exposures; on the other hand, the characteristics of non-invasive sampling also make EBA analysis has a broad application prospect in the field of human health monitoring and disease diagnosis. This paper used a combination of nylon 6 film coated with poly-tetrahydrofuran (PTHF) and a medical N95 mask to construct a convenient and direct sampling device, which can be used to collect caffeine ingested by humans non-invasively from EBA. Volunteers wore a mask for a defined period of time after consuming a certain amount of caffeine. The samples were next back-extracted with methanol and detected and analyzed using gas chromatography-high resolution mass spectrometry (GC-HRMS). The results showed that under the optimized analytical conditions, the PTHF-coated nylon 6 film was effective in collecting caffeine from human EBA, and the peak time of caffeine was 23.44 min. The mask-loaded coated device in this study has the advantages of being comfortable and efficient, safe and non-invasive as well as easy to operate, and by combining with mass spectrometry molecular techniques it can achieve high sensitivity and specificity analysis of trace components, which is expected to be used for the early diagnosis of respiratory diseases in clinical analysis.

Exploring accurate mass measurements in pixel-based chemometrics: Advancing coffee classification with GC-HRMS—A proof of concept study

This paper presents a study that assesses the application of chemometrics for classifying coffee samples in a quality control context. High-resolution and accurate mass measurements were utilized as input for pixel-based orthogonal partial least squares discriminant analysis (OPLS-DA) models. The compositional data were acquired through a fully automated workflow combining headspace solid-phase microextraction and gas chromatography-high-resolution mass spectrometry (GC-HRMS) using an FT-Orbitrap® mass analyzer. A workflow centered on accurate mass measurements was successfully utilized for group-type analysis, offering an alternative to methods relying solely on MS similarity searches. The predictive models underwent thorough evaluation, demonstrating robust multivariate classification performance. Five key coffee attributes, bitterness, acidity, body, intensity, and roasting level were successfully predicted using GC-HRMS data. The results revealed strong predictive accuracy across all models, ranging from 88.9 % (bitterness) to 94.4 % (roasting level). This study represents a significant advancement in automating methods for coffee quality control, notably increasing the predictive ability of the models compared to existing literature.

Comparison of data processing strategies using commercial vs. open-source software in GC-Orbitrap-HRMS untargeted metabolomics analysis for food authentication: thyme geographical differentiation and marker identification as a case study

Untargeted analysis of gas chromatography–high-resolution mass spectrometry (GC-HRMS) data is a key and time-consuming challenge for identifying metabolite markers in food authentication applications. Few studies have been performed to evaluate the capability of untargeted data processing tools for feature extraction, metabolite annotation, and marker selection from untargeted GC-HRMS data since most of them are focused on liquid chromatography (LC) analysis. In this framework, this study provides a comprehensive evaluation of data analysis tools for GC-Orbitrap-HRMS plant metabolomics data, including the open-source MS-DIAL software and commercial Compound Discoverer™ software (designed for Orbitrap data processing), applied for the geographical discrimination and search for thyme markers (Spanish vs. Polish differentiation) as the case study. Both approaches showed that the feature detection process is highly affected by unknown metabolites (Levels 4–5 of identification confidence), background signals, and duplicate features that must be carefully assessed before further multivariate data analysis for reliable putative identification of markers. As a result, Compound Discoverer™ and MS-DIAL putatively annotated 52 and 115 compounds at Level 2, respectively. Further multivariate data analysis allowed the identification of differential compounds, showing that the putative identification of markers, especially in challenging untargeted analysis, heavily depends on the data processing parameters, including available databases used during compound annotation. Overall, this method comparison pointed out both approaches as good options for untargeted analysis of GC-Orbitrap-HRMS data, and it is presented as a useful guide for users to implement these data processing approaches in food authenticity applications depending on their availability.Graphical

Identifying potential breath biomarkers for early diagnosis of papillary thyroid cancer based on solid-phase microextraction gas chromatography-high resolution mass spectrometry with metabolomics.

Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method CONCLUSION: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.

In Vivo and In Vitro Metabolic Fate and Urinary Detectability of Five Deschloroketamine Derivatives Studied by Means of Hyphenated Mass Spectrometry.

Ketamine derivatives such as deschloroketamine and deschloro-N-ethyl-ketamine show dissociative and psychoactive properties and their abuse as new psychoactive substances (NPSs) has been reported. Though some information is available on the biotransformation of dissociative NPSs, data on deschloro-N-cyclopropyl-ketamine deschloro-N-isopropyl-ketamine and deschloro-N-propyl-ketamine concerning their biotransformation and, thus, urinary detectability are not available. The aims of the presented work were to study the in vivo phase I and II metabolism; in vitro phase I metabolism, using pooled human liver microsomes (pHLMs); and detectability, within a standard urine screening approach (SUSA), of five deschloroketamine derivatives. Metabolism studies were conducted by collecting urine samples from male Wistar rats over a period of 24 h after their administration at 2 mg/kg body weight. The samples were analyzed using liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) and gas chromatography-mass spectrometry (GC-MS). The compounds were mainly metabolized by N-dealkylation, hydroxylation, multiple oxidations, and combinations of these metabolic reactions, as well as glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected. For the LC-HRMS/MS SUSA, compound-specific metabolites were identified, and suitable screening targets could be recommended and confirmed in pHLMs for all derivatives except for deschloro-N-cyclopropyl-ketamine. Using the GC-MS-based SUSA approach, only non-specific acetylated N-dealkylation metabolites could be detected.

Prevalence of Psychoactive Substance Use During Pregnancy in Argentine Women: A Pilot Study Testing Maternal Hair.

The use of psychoactive substances (PSs) during pregnancy is a major public health concern because of their increasing prevalence worldwide. This study examined the understudied issue of gestational PS consumption in a cohort of Argentine delivering mothers. A cross-sectional pilot study involving 51 women receiving delivery care was conducted at the Santa Rosa Hospital in La Pampa, Argentina. Information on maternal sociodemographic characteristics, pregnancy history, and drug use was obtained through standardized interviews. Maternal hair samples were analyzed for alcohol, tobacco, licit, illicit, and prescription substance biomarkers using ultra-high-performance liquid chromatography high-resolution mass spectrometry and gas chromatography mass spectrometry. During pregnancy, 49.0% of participants reported alcohol consumption, 25.5% reported tobacco use, and 23.5% reported cannabis use. Hair samples from 56.9% of the women were positive for illicit PSs, with the most frequent being cocaine (41.2%) and cannabis (15.7%). Among the women, 47.1% consumed alcohol during pregnancy. Of the 24 women with hair ethyl glucuronide ≥5 pg/mg, 33.3% drank until the end of gestation and 58.3% started a social drinking habit in the second half. The analysis also detected prescription substances (anticonvulsants, antidepressants, methadone, opioids, antihistamines, antiemetics, and analgesics), caffeine (70.6%), lidocaine, and levamisole, some of which were cocaine or opioid adulterants. This is the first study to objectively assess the consumption of licit and illicit PSs during pregnancy in Argentina. In contrast to most nearby countries, cocaine was the most detected illicit PS in this cohort of Argentine delivering women. This finding highlights the importance of regular monitoring of local trends in PS use during pregnancy.

Qualitative transformations of street-seized ecstasy over a decade: A case study in Rio de Janeiro (Brazil).

The illegal drug market is constantly evolving, with new drugs being created and existing ones being modified. Adulterants are often added to the mix, and the primary substance may be secretly replaced by a new one. Once-known tablets can now be vastly different from what they are sold as, all due to the pursuit of profit and evasion of current drug regulations. These alterations in drug composition pose a threat to society, as their effects are still not well understood. Therefore, it is crucial for police intelligence and public health development to obtain the chemical profiles of illicit drugs. This study presents the chemical fingerprinting of ecstasy tablets seized in the state of Rio de Janeiro (Brazil) between 2012 and 2021. The tablet samples were weighed, extracted, diluted with methanol, and acidified before analysis using gas chromatography high-resolution mass spectrometry and attenuated total reflection Fourier transform infrared spectroscopy. The major constituents found were MDMA and clobenzorex, with fewer occurrences of MDA, MDEA, and 2C-B. The results also indicate that the occurrence of mega-events in the study location impacted the chemical fingerprints of ecstasy. A total of 27 combinations of cutting agents, including caffeine, ephedrine, and anesthetics, were identified. Samples composed of clobenzorex were observed throughout the evaluated period in areas near highways, suggesting that this product is mainly used by truck drivers. These findings can help police intelligence units anticipate the behavior of the illicit market during major events, identify traffic routes, and support public health initiatives.

Chemical impurity profiling: Linkage of starting materials and an intermediate synthesis product of a carbamate chemical warfare agent

Establishing links between starting materials and products is highly valuable in the investigation of the use of toxic chemicals for illicit purposes. In this study, impurity profiling was performed on starting materials and their synthesis product, 2-([dimethylamino]methyl)pyridin-3-yl dimethylcarbamate, an intermediate compound in the production route for the carbamate class of Chemical Warfare Agents. The aim was to link the five commercial starting materials to the correct synthesis products. Initially, the intermediate compound was synthesized using different batches of the two starting materials (2 plus 3 batches), producing six unique combinations. All synthesis batches and the different starting materials were analysed by gas chromatography-high resolution mass spectrometry (GC-HRMS). Chemometrics analyses were conducted with principal component analysis and orthogonal projections to latent structures discriminant analysis to extract chemical impurity profiles and to build supervised classification models.Additionally, 12 test set samples, produced using the same starting materials by two different chemists in another laboratory, were analysed by GC-HRMS. A classification model able to distinguish all supplier combinations was successfully created and used to link the test set samples to their corresponding starting material.Furthermore, a new set of synthesis samples was extracted with a work-up procedure before analysis to investigate the effect of higher sample purity on the classification model. The results show that linking the synthesis products to their starting materials was successful for one of the starting materials, despite the purification procedure.

Exposure to Polybrominated Diphenyl Ethers and Risk of All-Cause and Cause-Specific Mortality

Polybrominated diphenyl ethers (PBDEs) are an important group of persistent organic pollutants with endocrine-disrupting properties. However, prospective cohort studies regarding the association of PBDE exposure with long-term health outcomes, particularly mortality, are lacking. To examine the association of environmental exposure to PBDEs with risk of all-cause and cause-specific mortality. This nationally representative cohort study used data from the National Health and Nutrition Examination Survey 2003 to 2004 and linked mortality information through December 31, 2019. Adults aged 20 years or older with available data on PBDE measurements and mortality were included. Statistical analysis was performed from February 2022 to April 2023. PBDE analytes in serum samples were measured using solid phase extraction and isotope dilution gas chromatography high-resolution mass spectrometry. All-cause mortality, cancer mortality, and cardiovascular mortality. This study included 1100 participants (mean [SE] age, 42.9 [0.6] years; proportion [SE] female, 51.8% [1.6%]; proportion [SE] Hispanic, 12.9% [2.7%]; proportion [SE] non-Hispanic Black, 10.5% [1.6%]; proportion [SE] non-Hispanic White, 70.8% [3.7%]; proportion [SE] other race and ethnicity, 5.8% [1.1%]). During 16 162 person-years of follow-up (median [IQR] follow-up, 15.8 [15.2-16.3] years; maximum follow-up, 17 years), 199 deaths occurred. Participants with higher serum PBDE levels were at higher risk for death. After adjustment for age, sex, and race and ethnicity, lifestyle and socioeconomic factors, and body mass index, participants with the highest tertile of serum PBDE levels had an approximately 300% increased risk of cancer mortality (HR, 4.09 [95% CI, 1.71-9.79]) compared with those with the lowest tertile of serum PBDE levels. No significant association of PBDE exposure with all-cause mortality (HR, 1.43 [95% CI, 0.98-2.07]) or cardiovascular mortality (HR, 0.92 [95% CI, 0.41-2.08]) was observed. In this nationally representative cohort study, PBDE exposure was significantly associated with an increased risk of cancer mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.

Structural elucidation of derivatives of polyfunctional metabolites after methyl chloroformate derivatization by high-resolution mass spectrometry gas chromatography. Application to microbiota metabolites

Metabolomics has become an essential discipline in the study of microbiome, emerging gas chromatography coupled to mass spectrometry as the most mature, robust, and reproducible analytical technique. Silylation is the most widely used chemical derivatization strategy, although it has some limitations. In this regard, alkylation by alkyl chloroformate offers some advantages, such as a rapid reaction, milder conditions, better reproducibility, and the generation of more stable derivatives. However, commercial spectral libraries do not include many of the alkyl derivatives, mainly for polyfunctional metabolites, which can form multiple derivatives. That introduces a huge bias in untargeted metabolomics leading to common errors such as duplicates, unknowns, misidentifications, wrong assignations, and incomplete results from which non-reliable findings and conclusions will be retrieved. For this reason, the purpose of this study is to overcome these shortcomings and to expand the knowledge of metabolites in general and especially those closely related to the gut microbiota through the thorough study of the reactivity of the different functional groups in real matrix derivatized by methyl chloroformate, a common representative alkylation reagent. To this end, a systematic workflow has been developed based on exhaustive structural elucidation, along with computational simulation, and taking advantage of the high sensitivity and high-resolution gas chromatography-mass spectrometry. Several empirical rules have been established according to chemically different entities (free fatty acids, amino acids, polyols, sugars, amines, and polyfunctional groups, etc.) to predict the number of derivatives formed from a single metabolite, as well as their elution order and structure. In this work, some methyl chloroformate derivatives not previously reported as well as the mechanisms to explain them are given. Extremely important is the interconversion of E- and Z- geometric isomers of unsaturated dicarboxylic acids (case of fumaric-maleic and case of citraconic-mesaconic acids), or the formation of cycled derivatives for amino acids, as well as common metabolites, as in the case of serine and cysteine, and many others.

Comprehensive two-dimensional gas chromatography-high resolution mass spectrometry for the detailed qualitative analysis of old vine Chenin blanc wine volatiles and comparison with young vine Chenin blanc wines

Old vine Chenin blanc (OVC) wines are produced from grapes harvested from vines older than 35 years, verified as Certified Heritage Vineyards in South Africa. This emerging premium wine style is of interest due to the purported unique sensory properties of these wines, including their complex aroma. There is however limited information available on the volatile constituents of these wines, which are primarily responsible for perceived aroma. The wine volatilome is exceedingly complex, and requires advanced analytical approaches to investigate. The present contribution reports the evaluation of comprehensive two-dimensional gas chromatography (GC × GC) as a powerful separation technique to gain qualitative insight into the volatile composition of OVC wines. Extraction of volatile compounds was performed using headspace solid-phase microextraction (HS-SPME), while the GC × GC separation was hyphenated to high speed high resolution time-of-flight MS (HR-TOF-MS) for compound identification. A representative set of eight Chenin blanc wines produced from young vines (YVC) was also analysed to investigate the potential use of GC × GCHR-MS data to differentiate these two wine styles based on differences in their volatile composition. The results confirm the utility of GC × GCHR-MS for the detailed qualitative analysis of wine volatiles, with a total of 277 compounds identified in the studied wines. 53 compounds were uniquely identified in the OVC samples, and 52 in YVC wines. Successful differentiation of the young- and old-vine wines was achieved based on tile-based Fisher (F) ratios and principal component analysis (PCA), although this differentiation could not be clearly linked to winemaking practices (wood maturation) or viticultural origin.