Negative Chemical Ionization Mode Research Articles

Exploring Negative Chemical Ionization of Per- and Polyfluoroalkyl Substances via a Liquid Electron Ionization LC-MS Interface.

Per- and polyfluoroalkyl substances (PFASs) are a class of aliphatic manufactured compounds comprising fluoro-chemicals with varied functional groups and stable carbon-fluorine bonds. They are defined as "forever chemicals" due to their persistent and bioaccumulative character. These substances have been detected in various environmental samples, including water, air, soil, and human blood, posing significant health hazards. High-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS) is typically employed for the analysis of PFASs. Negative chemical ionization (NCI) is generally coupled to gas chromatography (GC) and offers high selectivity and sensitivity for compounds containing electronegative atoms, such as PFASs. The liquid electron ionization (LEI) interface is an efficient mechanism developed to robustly couple a liquid flow rate from an LC system to an EI or a CI source. This interface has been successfully utilized for pesticide determination in UHPLC-LEI-CI in negative ion mode (NCI). This work aims to evaluate different parameters involved in the ionization of PFASs analyzed in LC-LEI-NCI and subsequently develop a method for their detection in real samples. The parameters considered for this study include (i) a comparison of different CI reagent gases (methane, isobutane, and argon); (ii) the use of acetonitrile as both the chromatographic solvent and CI reagent gas; (iii) the presence of water and formic acid as chromatographic mobile phase components; and (iv) the mobile phase flow rate. The optimal combination of these parameters led to promising results. Tentative fragmentation pathways of PFASs in NCI mode are proposed based on the dissociative electron capture mechanism.

Assessment of atmospheric pollution by oxygenated and nitrated derivatives of polycyclic aromatic hydrocarbons in two regions of the Czech Republic

In this study, a method for monitoring 16 representatives of nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) and six oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) in airborne particulate matter (PM) was developed and validated. Soxhlet extraction, followed by solid phase extraction (SPE) on silica, was used to isolate the target compounds. Instrumental analysis was performed by gas chromatography coupled with (tandem) mass spectrometry (GC-MS(/MS)) operated in electron impact (EI) and negative ion chemical ionization (NICI) modes. GC-EI-MS/MS was selected for further experiments due to its higher selectivity of measurement and ability to measure derivatives simultaneously with 20 commonly analyzed PAHs (EU + US EPA priority list). This is the first study documenting the simultaneous analysis of OPAHs, NPAHs, and parent PAHs in a single run. This analysis strategy was successfully validated at two concentration levels of artificial contamination, i.e., 0.8 and 4 ng per filter, with recoveries in the 70–104% range and less than 23% repeatability. The newly developed method was used for the analysis of 45 air samples from two cities in the Czech Republic, namely Ceske Budejovice and Most (a place with heavy industry), and two sampling seasons (February vs. May 2017). Five representatives were found in all samples from the oxy-PAH group, with 9,10-anthraquinone (9,10-ANTQ) being the most abundant (0.010–2.49 ng m−3 air). Three major nitro-PAHs, namely 9-nitroanthracene (9-nANT), 2-nitrofluoranthene (2-nFA), and 1-nitropyrene (1-nPYR), were found in 89%, 96%, and 33% of the samples, respectively, found in concentration ranges of <0.60–902, <0.60–276, and <0.60–117 pg m−3 air. Slightly higher levels of oxy- and nitro-PAHs were found in Ceske Budejovice compared to Most, but the difference was not statistically significant (p-value >0.05). A statistically significant difference was observed between February and May, where the concentrations in February were up to 20 and 50 times higher for individual oxy- and nitro-PAHs, respectively, in both regions. The diagnostic ratio 2-nFA/1-nPYR >5 showed that indirect emissions were the primary nitro-PAH source in Most of nitro-PAHs in Most and in both sampling campaigns. In Ceske Budejovice, the opposite trend was observed in winter, i.e. 2-nFA/1-nPYR <5, indicating direct emissions as the main source. In summary, direct emissions of OPAHs and NPAHs originate from fossil (transportation-related) and solid fuel (heating-related) combustion. In contrast, indirect emissions are related to atmospheric reactions of PAHs with OH radicals (spring, winter) and NO3 radicals (winter). The total TEQB[a]P was higher in winter than spring, with higher inhalation cancer risk.

Short- and medium-chain chlorinated paraffins in T-shirts and socks

The short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) are complex mixtures of persistent compounds used mainly as plastic additives. They can have a negative impact on human health as they are suspected of disrupting the endocrine system and being carcinogenic, which is why monitoring their presence in the human environment is desirable.Clothing was selected for this study because they are produced in large quantities worldwide and the final products are worn for long periods throughout the day, in direct contact with human skin. The concentrations of CPs in this type of sample have not been sufficiently reported.We determined SCCPs and MCCPs in 28 samples of T-shirts and socks by gas chromatography coupled with high-resolution mass spectrometry in negative chemical ionisation mode (GC–NCI–HRMS). CPs were found above the limits of quantification in all samples, with concentrations ranging from 33.9 to 5940 ng/g (mean 1260 ng/g, median 417 ng/g). The samples with a substantial proportion of synthetic fibres contained higher CP concentrations (22 times higher mean for SCCPs and 7 times higher mean for MCCPs) than garments composed exclusively of cotton.Finally, the effect of washing in the washing machine was investigated. The individual samples behaved differently: (i) excessively emitting CPs; (ii) being contaminated; (iii) retaining the original CP levels. The CP profiles also changed for some samples (with a substantial proportion of synthetic fibres and samples composed exclusively of cotton).

The use of gas chromatography – high resolution mass spectrometry for suspect screening and non-targeted analysis of per- and polyfluoroalkyl substances

This study is a workflow development for the analysis, identification, and categorization of per- and polyfluoroalkyl substances (PFAS) using gas chromatography-high resolution mass spectrometry (GC-HRMS) with non-targeted analysis (NTA) and suspect screening techniques. The behavior of various PFAS in a GC-HRMS was studied with regards to retention indices, ionization susceptibility, fragmentation patterns, etc. A custom PFAS database was constructed from 141 diverse PFAS. The database contains mass spectra from electron ionization (EI) mode, as well as MS and MS/MS spectra from positive and negative chemical ionization (PCI and NCI, respectively) modes. Common fragments of PFAS were identified across a diverse set of 141 PFAS analyzed. A workflow for suspect screening of PFAS and partially fluorinated products of incomplete combustion/destruction (PICs/PIDs) was developed which utilized both the custom PFAS database and external databases. PFAS and other fluorinated compounds were identified in both a challenge sample (designed to test the identification workflow) and incineration samples suspected to contain PFAS and fluorinated PICs/PIDs. The challenge sample resulted in a 100% true positive rate (TPR) for PFAS which were present in the custom PFAS database. Several fluorinated species were tentatively identified in the incineration samples using the developed workflow.

Comprehensive non-target screening of biomagnifying organic contaminants in the Baltic Sea food web

High-resolution mass spectrometry (HRMS) based non-target screening (NTS) is a powerful approach for the simultaneous determination of multiple environmental contaminant classes in complex biota samples. In this study, trophic biomagnification factor (TMF) directed NTS was performed to find and (tentatively) identify known, emerging, and new chemical contaminants that are persistent and biomagnify in Baltic Sea biota. The investigated food web included seven species: one filter feeder (blue mussel, Mytilus edulis), two fish (eelpout, Zoarces viviparous; herring, Clupea harengus), two marine mammals (harbor porpoise, Phocoena phocoena; grey seal, Halichoerus grypus) and two birds (guillemot, Uria aalge; white-tailed sea eagle, Haliaeetus albicilla). The NTS procedure included extraction with organic solvent mixtures, two-step high-resolution gel permeation chromatography clean-up, Florisil® fractionation, gas chromatography (GC) HRMS analysis in electron ionization (EI) and electron capture negative ion chemical ionization (ECNI) modes, and NTS data processing. The latter was performed differently for the EI and ECNI data: the EI data were treated using a flexible and highly automated TMF-directed NTS workflow, whereas the ECNI data were treated with a simpler and less automated workflow that specifically screened for brominated compounds. The two workflows collectively revealed biomagnification (statistically significant TMF values) of >250 tentatively identified compounds, including legacy persistent organic pollutants (POPs), such as PCBs and PCB-related compounds, DDT and its metabolites, and organochlorine pesticides (OCPs), contaminants of emerging concern (CECs), and halogenated natural products (HNPs). Among the tentatively identified CECs, nine have not previously been reported in environmental biota samples. These included four polymer additives (used as antioxidants, rubber additives or plasticizers) and two cosmetic product additives (ethyl myristate and isopropyl palmitate). The CECs should be prioritized for future structure verification and quantification using reference standards.

Development of a Solid-Phase Extraction Method Based on Biocompatible Starch Polyurethane Polymers for GC-MS Analysis of Polybrominated Diphenyl Ethers in Ambient Water Samples.

A new solid-phase extraction (SPE) method for the extraction, enrichment, and analysis of eight polybrominated diphenyl ethers (PBDEs) in water was developed. The current approach involves using a cross-linked starch-based polymer as an extraction adsorbent and determining the PBDE analytes of interest using gas chromatography-mass spectrometry in negative chemical ionization mode (GC-NCI-MS). The starch-based polymer was synthesized by the reaction of soluble starch with 4,4′-methylene-bis-phenyldiisocyanate as a cross-linking agent in dry dimethylformamide. Various parameters impacting extraction efficiencies, such as adsorbent quantity, sample volumes, elution solvents and volumes, and methanol content, were carefully optimized. The 500 mg of starch-based polymer as an adsorbent used to extract 1000 mL of spiked water, presented high extraction recoveries of eight PBDEs. The linearity of the extraction process was investigated in the range of 1–200 ng L−1 for BDE-28, 47, 99, 100, and 5–200 ng L−1 for BDE-153, 154, 183, and 209, with coefficients of determination (r2) exceeding 0.990 for all PBDEs. The limits of detection (LODs) ranged from 0.06 to 1.42 ng L−1 (S/N = 3) and the relative standard deviation values (RSD) were between 3.6 and 9.5 percent (n = 5) under optimum conditions. The method was successfully used to analyze river and lake water samples, where it exhibited acceptable recovery values of 71.3 to 104.2%. Considering the excellent analytical performance and comparative cost advantage, we recommend the developed starch-based SPE method for routine extraction and analysis of PBDEs in water media.

Are fish oil-based dietary supplements a significant source of exposure to chlorinated paraffins?

Chlorinated paraffins (CPs) are an emerging group of environmental pollutants associated with adverse effects on human health (such as endocrine disruption and possible carcinogenicity). CPs are classified into several groups: short- (SCCPs), medium- (MCCPs) and long-chain chlorinated paraffins (LCCPs). In this study, CPs were determined in fish oil-based omega-3 dietary supplements (DS) representing widely consumed products that might be contaminated with various lipophilic contaminants including CPs. The CPs were isolated from DS (n = 85) by solid phase extraction. The SCCPs and MCCPs were determined by gas chromatography coupled with high-resolution mass spectrometry operated in a negative chemical ionisation mode. The LCCPs (up to C21) were screened using supercritical fluid chromatography coupled with high-resolution mass spectrometry with electrospray ionisation operated in negative mode. The CP concentrations varied from <0.01 to 56.48 μg/g fat for SCCPs (median 0.12 μg/g fat; limit of quantification, LOQ, for SCCPs was exceeded in 51 out of 85 samples) and from <0.03–89.08 μg/g fat for MCCPs (median 0.26 μg/g fat; LOQ for MCCPs was exceeded in 66 out of 85 samples), respectively. The LCCPs were not quantified in this study, nevertheless their limit of detection (0.5 μg/g fat) was exceeded in 7 out of 85 samples. Due to high levels of CPs, DS might pose as a significant source of CPs exposure to some population groups.

Simultaneous Quantitative Determination of Synthetic Cathinone Enantiomers in Urine by GC-NCI-MS/MS using Menthylchloroformate as Chiral Derivatization Reagent

Development and validation of a new analytical method for enantioseparation and quantitation of synthetic cathinones is reported using a chiral derivatization agent (CDA) and GC-MS triple quadrupole mass spectrometry with negative chemical ionization (NCI) mode. Indirect separation of ten synthetic cathinone compounds has been achieved using a commercially available optically pure CDA called (1R)-(-)-menthylchloroformate (MCF). MCF was capable of converting synthetic cathinone enantiomers into diastereoisomers, which were later separated with good resolution on an ultra-inert 60 m achiral stationary phase column. An internal standard (IS), 3-methylmethcathinone (3-MMC) was used for quantitation of synthetic cathinone diastereoisomers. Method validation in terms of calibration curve linearity, sensitivity in terms of limits of detections (LODs), limits of quantitation (LOQs), interday and intra-day reproducibility, and recoveries has been obtained for the ten synthetic cathinone compounds that were analyzed simultaneously as a mixture after being spiked in urine. It was found that LOD’s and LOQ’s for the ten synthetic cathinones mixture in urine were in the ranges of 0.004-3.678 ppm and 0.012-11.14 ppm respectively. The results of four synthetic cathinones (Buphedrone, 3-MethylBP,3,4-DMEC, and Butylone) derivatized with MCF were compared with the same compounds derivatized with N-trifluoroacetyl-L-prolyl chloride (L-TPC). It was found that the later was more sensitive in terms of LOD and LOQ than the former method.

The pollution profiles and human exposure risks of chlorinated and brominated PAHs in indoor dusts from e-waste dismantling workshops: Comparison of GC–MS, GC–MS/MS and GC × GC–MS/MS determination methods

The toxicities of some chlorinated and brominated polycyclic aromatic hydrocarbons (X-PAHs) are higher than their corresponding parent PAHs. However, the identification and quantitation of X-PAHs in environment are still changeable and limitedly reported. To develop a robust method for routine analysis of X-PAHs in environmental samples, the determination of 34 X-PAHs was performed and compared using different instruments, including gas chromatography-mass spectrometry (GC–MS), gas chromatography-tandem mass spectrometry (GC–MS/MS) in both electron ionization (EI) and negative chemical ionization (NCI) modes, and comprehensive two-dimensional gas chromatograph-tandem mass spectrometer (GC × GC–MS/MS). GC-EI-MS/MS possessed the highest sensitivity with method detection limits of 2.00–40.0 and 2.00–20.0 pg/g dry weight (dw) for Cl-PAHs and Br-PAHs, respectively. This validated method was then applied to analyze X-PAHs in indoor dusts from a typical e-waste dismantling workshop, and the concentrations of Σ18Br-PAHs (8.80–399 ng/g dw) were higher than Σ16Cl-PAHs (7.91–137 ng/g dw). The toxicity equivalency quantities (TEQs) of Cl-PAHs at e-waste dismantling workshop and Br-PAHs at raw materials crushing workshop showed the highest values of 176 and 453 pg·TEQ/g, respectively. Cl-PAHs and Br-PAHs posed a potential health risk to workers through dust ingestion in workshops. Further attention should be payed to the formation mechanism of X-PAHs and the health risk.

High Resolution GC-Orbitrap-MS Metabolomics Using Both Electron Ionization and Chemical Ionization for Analysis of Human Plasma.

Gas chromatography-mass spectrometry (GC-MS) platforms are typically run in electron ionization (EI) mode for mass spectral matching and metabolite annotation. With the advent of high resolution mass spectrometry (HRMS), soft ionization techniques such as chemical ionization (CI) may provide additional coverage for compound identification. We evaluated NIST SRM 1950 pooled plasma reference sample using a HRGC-MS instrument [GC-Orbitrap-MS with electron ionization (EI), positive chemical ionization (PCI), and negative CI (NCI) capabilities] for metabolite annotation and quantification to assess the suitability of the platform for routine discovery metabolomics. Using both open source and vendor workflows, we validated the spectral matches with an in-house spectral library (Wake Forest CPM GC-MS spectral and retention time libraries) of EI-MS and CI-MS/MS spectra obtained from chemical standards. We confidently [metabolomics standards initiative (MSI) confidence level 2] identified 263, 93, and 65 metabolites using EI, PCI, and NCI modes, respectively, of which 270 metabolites (64%) were validated using our Wake Forest CPM GC-MS spectral libraries. When compared to published LC-MS-based efforts using the same NIST SRM 1950 plasma sample, there was only 17% overlap between the two platforms. In addition, the metabolomics analysis of community approved standard human plasma demonstrated the ability of EI- and CI-MS modes of analysis using a HRGC-MS platform to enable reproducible and interoperable spectral matching.

Selective Gas Chromatography Mass Spectrometry Method for Ultratrace Detection of Selenocyanate

The recent interest in the determination of selenocyanate (SeCN-) in wastewater systems has spurred the development of analytical methods for its determination at the ultratrace level. Since most of the current procedures require complex and costly instrumental configurations, we have developed a simple and rapid gas chromatography tandem mass spectrometry (GC/MS/MS) method able to detect SeCN- in water samples with a LOD of 0.1 ng/g Se. A 1 mL volume of aqueous sample was buffered with sodium bicarbonate and treated with triethyloxonium tetrafluoroborate for conversion of the analyte into volatile EtSeCN. The derivatization yield was higher than 90%, and it could tolerate concentrations of chloride or sulfate up to 2%. The EtSeCN was extracted in chloroform and could be detected in electron ionization and also in negative chemical ionization mode with a further gain in signal-to-noise ratio by a factor of 2. The method was applied for the analysis of natural waters with quantitation of SeCN- in the low ng/g region. The Se13C15N- internal standard could be used for isotope dilution. Quantitative spike recoveries of 1 ng/g Se were obtained from seawater and river water, and 1 ng/g Se could be quantified within a standard uncertainty of 15%.

Influence of cosmetic hair treatments on cannabinoids in hair: Bleaching, perming and permanent coloring

Various cosmetic hair manipulations are known to interfere with drug of abuse concentrations in hair. It is important to evaluate the effects of cosmetic hair treatments as they can influence quantitative hair results. Only one study showed a significant decrease of THC after bleaching and coloring.The aim of the study was to investigate the effect of bleaching, perming and dyeing treatment on d-9-tetrahydrocannabinol (THC), but also Cannabidiol (CBD), Cannabinol (CBN) and 11-nor-D9-tetrahydrocannabinol-9-carboxylic acid (THC−COOH) in hair.Thirty THC-positive hair samples were selected in this study. A single hair lock was divided in 2 separate locks and the proximal 3 cm segment was analyzed. One lock served as control while the other lock was bleached, permed or dyed respectively. Hair was analyzed using a routine method including cleaning, treatment of hair with NaOH and 2 different SPE extractions for THC, CBN, CBD and THC−COOH respectively. Analysis was performed with routine methods using GC/MS-MS in electron impact (EI) mode for THC, CBN and CBD or negative chemical ionization (NCI) mode for THC−COOH after PTV-injection.Bleaching and perming reduced all cannabinoids concentration in hair; THC was more affected than THC−COOH, CBN and CBD. Bleaching caused strong chemical degradation on cannabinoids, while perming exerted more a leaching out effect. Permanent colorings in single applications had only little effects on cannabinoids.Finally this study highlights the importance of considering bleaching and perming for the correct interpretation of hair results.

Determination of polybrominated diphenyl ethers and novel brominated flame retardants in human serum by gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry

The accurate detection of brominated flame retardants (BFRs) in humans is an area of high scientific interest and regulatory need due to their potential toxicity. The instrumental analysis of BFRs was commonly performed on gas chromatography-mass spectrometry (GC-MS) operating in electron ionization (EI) or negative chemical ionization (NCI) modes. However, soft ionization techniques, such as atmospheric pressure chemical ionization (APCI), may be more suitable for the analysis of BFRs because the BFRs show high fragmentation in EI and low selectivity in NCI. Additionally, accurate quantifications of BFRs in complex matrices is challenging due to their low concentrations and therefore, a highly sensitive technique is desperately needed. In this study, a new methodology based on gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (GC-APCI-MS/MS) analysis was developed for the determination of thirteen BFRs (eight usually monitored polybrominated diphenyl ethers (PBDEs) congeners and five additional novel BFRs) in human serum. The primary task was to evaluate the potential of the GC-APCI-MS/MS technique for the trace analysis of BFRs in human serum. The results of the spiked recovery test using fetal bovine serum showed that mean recoveries of the analytes ranged from 83.4% to 118% with reduced swing differential signaling (RSDs) of ≤21.1%. The methodological limits of detection (mLOD) of the analytes ranged from 0.04 to 30 pg/mL, and these values were at least one order of magnitude lower than those estimated by the authors in a previous study using GC-NCI-MS or GC-EI-MS/MS, indicating that GC-APCI-MS/MS is more sensitive. Specially, compared to GC-NCI-MS and GC-EI-MS/MS, when GC-APCI-MS/MS was used for the detection of highly brominated BFRs, such as BDE-209 and decabromodiphenyl ethane (DBDPE), a notable improvement in sensitivity and reliability was obtained using a deactivated capillary column connected to the analytical column as the transfer line and maintaining a high temperature to improve the chromatographic behaviors. The developed methodology was successfully used for the analysis of BFRs in human serum collected from residents living in a BFR production area and Beijing.

A hollow microporous organic network as a fiber coating for solid-phase microextraction of short-chain chlorinated hydrocarbons

A solid-phase microextraction (SPME) fiber coated with a hollow microporous organic network (H-MON) was fabricated for the analysis of short-chain chlorinated paraffins (SCCPs). The sorbent was prepared by reacting tetra(4-ethynylphenyl)methane and 1,4-diiodobenzene using bis-(triphenylphosphine) palladium(II) as the catalyst in the presence of silica sphere templates, which then were removed by hydrofluoric acid. The SCCPs were quantified by GC-MS working in the negative chemical ionization mode. The H-MON has a high specific surface (701m2·g-1) and microporosity (pore size <2nm). Extraction temperature, extraction time, and ionic strength of the sample solutions were optimized by using the Box-Behnken design. The head-space SPME exhibits better extraction performance than the direct immersion mode. Under optimal working conditions, the detection limit (3 times of the standard deviation) is 0.03ng·mL-1 in the water samples. Response is linear in the 0.05-10ng·mL-1 concentration range. Repeatability and reproducibility, expressed as the relative standard deviations, ranged from 4.6 to 11.0%. The method was successfully applied in the analysis of SCCPs in water, sediments, organisms, and atmospheric particulate matter samples. Graphical abstract Schematic of the fabrication of a hollow microporous organic network (H-MON) on stainless steel fibers for use inSPME. The method was applied to the determination ofshort-chain chlorinated paraffins in biological, environmental water and atmospheric particulate matter (PM2.5) samples.

Determination of total dissolved nitrogen in seawater by isotope dilution gas chromatography mass spectrometry following digestion with persulfate and derivatization with aqueous triethyloxonium

In this study, we propose a novel approach for the determination of total dissolved nitrogen (TDN) in seawater combining high-precision isotope dilution GC–MS with persulfate digestion. A 2 mL sample aliquot was digested with an alkaline solution of persulfate to convert nitrogen containing compounds to nitrate. Digested samples were spiked with 15NO3− internal standard and treated with aqueous triethyloxonium to convert the analyte into volatile EtONO2. This derivative was readily separated from the matrix under gaseous form and could be sampled from the headspace before GC–MS analysis. The resulting chromatograms showed a stable flat baseline with EtONO2 as the only eluting peak (retention time 2.75 min on a DB 5.625 column). Such an approach provides specificity and obviates the shortcomings of current detection methods employed to analyze seawater samples after digestion with persulfate. In negative chemical ionization mode, the method reached a detection limit of 0.5 μmol/kg TDN (7 ng/g N) and could be applied to quantify seawater samples with 1–25 μmol/kg TDN. On the upper end of the range, quantitation could be repeated within 1%, whereas on a 6 μmol/kg TDN sample repeatability was 2.3% on eight measurements. The method was employed in two proficiency testing exercises providing results in agreement with consensus values. We investigated the impact of reagent blank and we implemented a blank-matching optimal design to account for such contribution. Finally, we performed a study on the yield of persulfate oxidation for organic and inorganic nitrogen compounds typically present in seawater. Whilst nitrite and ammonium are fully converted to nitrate, more complex organic molecules showed recoveries varying from 70% to 100%.

Variability on ethyl glucuronide concentrations in hair depending on sample pretreatment, using a new developed GC–MS/MS method

Quantitative determination of ethyl glucuronide in keratin matrix, particularly in hair samples, provides a significant contribution to the evaluation of the extent of ethanol intake. The first-choice method to carry out this analysis is LC–MS/MS, but other techniques may be used. The aim of this work is: a) to develop and validate a GC–MS/MS method for ethyl glucuronide determination in hair; b) to compare GC–MS/MS and LC–MS/MS in analysis of real samples; c) to compare EtG concentration obtained after hair cutting and pulverization.About 30 mg hair samples were washed, pulverized and soaked in 1 ml deionized water. After incubation, the solution was purified through a SPE anion exchange cartridge; the eluate was dried under nitrogen stream, derivatized with PFPA and reconstituted in n-hexane. Then, the sample was injected in the GC–MS/MS system, operating in negative chemical ionization mode and in selected reaction monitoring. The two most intense transitions were used to monitor ethyl glucuronide and deuterated internal standard. All the validation parameters fulfilled the international acceptance criteria. LOD and LOQ were set at 2.0 and 3.0 pg/mg respectively.This method was applied to 194 hair samples collected from teetotallers and alcohol consumers and represents a suitable alternative to LC–MS/MS for the determination of EtG in hair samples, in particular when scarce quantity of hair is available. This study confirmed that pulverization of hair increases the concentration of EtG, but some variability of EtG levels remains probably due to the presence of non-homogeneous material even though pulverization.

High-sensitivity quantification of serum androstenedione, testosterone, dihydrotestosterone, estrone and estradiol by gas chromatography–tandem mass spectrometry with sex- and puberty-specific reference intervals

BackgroundAndrogen and estrogen determinations serve as important diagnostic markers in a variety of clinical conditions. However, one challenge is to enhance assay sensitivity for determination in the lowest range, such as in prepubertal children.We here present a recently developed gas chromatography–tandem mass spectrometry (GC–MS/MS) method for determination of androstenedione (A4), dihydrotestosterone (DHT), testosterone (T), estrone (E1), and estradiol (E2) in children, which we have compared with the sensitive radioimmunoassays; E2 extraction-RIA and T-RIA. MethodsSteroids were extracted in ethyl acetate n-hexane solution from serum spiked with isotopically labeled internal standard and derivatized sequentially with pentafluorobenzyl bromide, pentafluorobenzyl hydroxylamine and pentafluoropropionic acid anhydride and analyzed by GC–MS/MS using a triple quadrupole mass spectrometer operated in negative chemical ionization mode. Leftover routine samples (n = 414) were used to evaluate the concordance between GC–MS/MS and RIAs and the validity of GC–MS/MS for pediatrics; of these samples, 101 were from seemingly healthy children. Pubertal stage was recorded for reference interval evaluation. ResultsLower limit of detection for A4, T, DHT, E1, and E2 were 0.1 nmol/L, 0.1 nmol/L, 27 pmol/L, 9 pmol/L, and 2 pmol/L, respectively. Good agreement was found between GC–MS/MS and T-RIA (r = 0.98) as well as between GC–MS/MS and E2 extraction-RIA (r = 0.98, for E2 concentrations above 14 pmol/L). In boys, T and DHT increased significantly from prepuberty throughout pubertal development, and in girls the same increase was observed for E1 and E2. The greatest increase in A4 for both genders, as well as E1 and E2 in boys and T and DHT in girls, occurred in mid to late puberty. ConclusionsWe report the development of a GC–MS/MS method sensitive enough to accurately determine serum levels of androgens and estrogens in children.

Core–shell indium (III) sulfide@metal-organic framework nanocomposite as an adsorbent for the dispersive solid-phase extraction of nitro-polycyclic aromatic hydrocarbons

A core–shell discoid shaped indium (III) sulfide@metal-organic framework (MIL-125(Ti)) nanocomposite was synthesized by a solvothermal method and explored as an adsorbent material for dispersive solid-phase extraction (d-SPE). The as-synthesized sorbent was characterized by scanning electron microscopy, energy-dispersive spectroscopy, transmission electron microscopy, powder X-ray diffraction, N2 adsorption–desorption analysis, and Fourier transform infrared spectroscopy. The extraction performance was evaluated by the d-SPE of 16 nitro-polycyclic aromatic hydrocarbons (NPAHs) from water samples. The analysis was carried out by gas chromatography (GC) coupled with triple quadruple mass spectrometer in negative chemical ionization (NCI) mode. The selected ion monitoring (SIM) was used in the quantification of the target NPAHs. Extraction factors affecting the d-SPE, including the ionic strength, extraction temperature, and extraction time were optimized by the response surface methodology. The developed d-SPE method showed good linear correlations from 10 to 1000 ng L−1 (r > 0.99), low detection limits (2.9–83.0 ng L−1), satisfactory repeatability (relative standard deviation of <10%, n = 6), and acceptable recoveries (71.3%–112.2%) for water samples. The developed method was used for the food and environmental sample analysis. The results demonstrated that the method could be used for sample preparation of trace NPAHs in real samples.

Simultaneous Quantitative Determination of Synthetic Cathinone Enantiomers in Urine and Plasma Using GC-NCI-MS.

Development and validation of sensitive and selective method for enantioseparation and quantitation of synthetic cathinones is reported using GC-MS triple quadrupole mass spectrometry with negative chemical ionization (NCI) mode. Indirect chiral separation of thirty-six synthetic cathinone compounds has been achieved by using an optically pure chiral derivatizing agent (CDA) called (S)-(−)-N-(trifluoroacetyl)pyrrolidine-2-carbonyl chloride (L-TPC), which converts cathinone enantiomers into diastereoisomers that can be separated on achiral columns. As a result of using Ultra Inert 60 m column and performing slow heating rate (2°C/min) on the GC oven, an observed enhancement in enantiomer peak resolution has been achieved. An internal standard, (+)-cathinone, was used for quantitation of synthetic cathinones. Method validation in terms of linearities and sensitivity in terms of limits of detection (LODs), limits of quantitation (LOQs), recoveries, and reproducibilities has been obtained for fourteen selected compounds that examined simultaneously as a mixture after being spiked in urine and plasma. It was found that the LOD of the fourteen synthetic cathinones in urine was in the range of 0.26–0.76 µg/L, and in plasma, it was in the range of 0.26–0.34 µg/L. While the LOQ of the mixture in urine was in the range of 0.86–2.34 µg/L, and in plasma, it was in the range of 0.89–1.12 µg/L. Unlike the electron impact (EI) ion source, NCI showed better sensitivity by two orders of magnitude by comparing the obtained results with the recently published reports for quantitative analysis and enantioseparation of synthetic cathinones.

Gas chromatography/negative chemical ionization mass spectrometry of transfluthrin in rat plasma and brain.

Transfluthrin is a relatively non-toxic rapid-acting synthetic pyrethroid insecticide. It is widely used in household and hygiene products. A sensitive and accurate bioanalytical method is required for quantification of its concentration in plasma and its potential target organ, the brain for studies to assess its health effects and toxicokinetics in mammals. The samples were prepared by liquid-liquid extraction. Gas chromatography mass spectrometry (GC/MS) analysis was performed for the determination of transfluthrin in biological samples with an overall method run time of 15min. Transfluthrin was quantified using selected-ion monitoring (SIM) in the negative chemical ionization (NCI) mode. Chromatographic separation was achieved using a Zebron® ZB5-MS GC column operating with 1mL/min constant flow helium. Cis-Permethrin was used as the internal standard. The method was validated to be precise and accurate within the linear range of 1.0-400.0ng/mL in plasma and 4.0-400.0ng/mL in brain homogenate, based on a 100μL sample volume for both matrices. This method was applied to samples following administration of a 10mg/kg oral dose to male adult rats. The plasma concentrations were observed to be 11.70±5.69ng/mL and brain concentrations 12.09±3.15ng/g when measured 2h post-dose. A rapid GC/NCI-MS method was demonstrated to be sensitive, specific, precise and accurate for the quantification of transfluthrin in rat plasma and brain. The optimized method was successfully used to quantify the rat plasma and brain concentrations of transfluthrin 2h after the oral dosing of Sprague-Dawley rats.