Magnetic Sector High Resolution Mass Research Articles

Development of a field-deployable analytical workflow for determining current status and indicative human health risks at a historic dl-POPs hotspot

This paper introduces an integrated workflow that effectively evaluates environmental and health risks of dioxin-like Persistent Organic Pollutants (dl-POPs) at industrial hotspot regions. The developments of validated, cost effective and user-friendly analytical strategies which can be field deployable are quintessential for routine monitoring of dl-POPs, particularly in developing countries. This study addresses the lacunae by enabling an exclusive gas chromatography triple quadrupole mass spectrometer based analytical workflow substituting conventional magnetic sector high resolution mass spectrometer technique and validated the methodology as per the European Union regulation 644/2017. The viable monitoring utility of the methodology for predicting enviro-food-health nexus was field-tested by analyzing fish and sediment samples from the Eloor-Edayar industrial belt, a solitary POPs hotspot in India. The profiles of congeners indicate that dl-POPs were formed through precursor pathways, suggesting the potential release of chlorinated precursor species from surrounding industrial area as the root cause. Fish samples from hotspots were observed to have 8 times higher levels of polychlorinated dibenzo-p-dioxin/furans (PCDD/Fs) and 30 times higher levels of polychlorinated biphenyls (PCBs) than the control sites. A strong statistically significant (p < 0.05) positive correlation was observed between dl-POPs levels in fish and sediment samples at the study site and the Biota sediment accumulation factors for PCDD/Fs and dl-PCBs ranged from 0.019 to 0.092 and 0.004 to 0.671 respectively. The estimated weekly intake from fish consumption in the study region was observed to be 3 to 24 times higher than the maximum levels set by the European food safety authority (2 pgTEQ kg−1bwweek−1). Hence, the periodic surveillance of dl-POPs employing user friendly/validated confirmatory tools stands highly imperative to safeguard human health and environment. Keywords: Dioxin and PCBs, GC-MS/MS, POPs Hotspot, Biota-sediment accumulation factor, Correlation analysis, Health risk assessment.

Multi-analyte method for the analysis of legacy and alternative brominated and chlorinated flame retardants in food products of animal origin using gas chromatography - magnetic sector high resolution mass spectrometry

An analytical method was developed and validated for the analysis of 32 halogenated flame retardants (HFRs), including 13 polybrominated diphenyl ethers (PBDEs), 9 dechlorane-related compounds (DRCs) and 10 of the so-called alternative BFRs in food samples of animal origin. Gas chromatography (GC) coupled with magnetic sector high resolution mass spectrometry (HRMS) was used for the instrumental analysis. Intralaboratory validation of the developed method was performed in terms of recovery, repeatability, linear calibration ranges, instrumental and method limits of quantitation (i-LOQ and m-LOQ). Where possible, trueness was verified by the analysis of reference materials (RMs). For analytes with available isotopically labeled surrogates, recoveries in the range of 70–120% and repeatability rates below 20% were observed, while for compounds quantitated using absolute calibration the values of recovery ranged from 59 to 153% and the repeatability in terms of RSDs was in the range of 1–26%. The values measured for the four analyzed RMs agreed with the provided consensus values, revealing that the recovery of reference concentrations for compounds with assigned consensus values was in 72–119% range. The elaborated method met the sensitivity criteria according to the Commission Recommendation, 2014/118/EU on the monitoring of BFRs in food products. The developed method was successfully applied for the analysis of numerous food samples. The analyses revealed ubiquitous presence of PBDEs and the majority of DRCs in the analyzed samples, while alternative BFRs were detected only occasionally.

Evaluation of multiple alternative instrument platforms for targeted and non-targeted dioxin and furan analysis.

The use of gas chromatography coupled to high-resolution magnetic sector mass spectrometers (GC-HRMS) is well established for dioxin and furan analysis. However, the use of gas chromatography coupled to triple quadrupole (MS/MS) and time of flight (TOF) mass spectrometers with atmospheric pressure ionization (API) and traditional electron ionization (EI) for dioxin and furan analysis is emerging as a viable alternative to GC-HRMS screening. These instruments offer greater versatility in the lab for a wider range of compound identification and quantification as well as improved ease of operation. The instruments utilized in this study included 2 API-MS/MS, 1 traditional EI-MS/MS, an API-quadrupole time of flight mass spectrometer (API-QTOF), and a EI-high-resolution TOF (EI-HRTOF). This study compared these 5 instruments to a GC-HRMS using method detection limit (MDLs) samples for dioxin and furan analysis. Each instrument demonstrated acceptable MDL values for the 17 chlorinated dioxin and furans studied. The API-MS/MS instruments provide the greatest overall improvement in MDL value over the GC-HRMS with a 1.5 to 2-fold improvement. The API-QTOF and EI-TOF demonstrate slight increases in MDL value as compared with the GC-HRMS with a 1.5-fold increase. The 5 instruments studied all demonstrate acceptable MDL values with no MDL for a single congener greater than 5 times that for the GC-HRMS. All 5 instruments offer a viable alternative to GC-HRMS for the analysis of dioxins and furans and should be considered when developing new validated methodologies.

Automated and simultaneous determination of priority substances and polychlorinated biphenyls in wastewater using headspace solid phase microextraction and high resolution mass spectrometry

The re-use of wastewater has been in growing demand but a possible negative feature is the possibility of organic pollutants being present after its treatment. In order to control the presence of contaminants in wastewater, a completely automated methodology capable of determining a total of 55 organic pollutants including pesticides, polycyclic aromatic hydrocarbons (PAHs), brominated diphenyl ethers (BDEs) and polychlorinated biphenyls (PCBs) at ultra-trace levels has been developed. The proposed method is based on an on-line combination of headspace solid phase microextraction (HS-SPME) and gas chromatography coupled to double-focusing magnetic sector high resolution mass spectrometry (GC-HRMS). HS-SPME as well as GC-HRMS conditions were optimized so as to achieve maximum extraction efficiency and sensitivity which was reinforced by using multiple ion detection (MID) as acquisition mode. Special attention was directed to fiber conditioning and stability by calorimetric and scanning electron microscopy (SEM) analysis.Method validation showed good linearity (R2 > 0.99), recoveries between 86 and 113%, relative standard deviation (RSD) values < 20% for intra-day and inter-day precision and quantification limits (LOQs) between 0.01 and 350 ng L−1. Finally, the proposed method was successfully applied to wastewater samples revealing the presence of PAHs and PCBsS and certain pesticides, mainly anthracene, chlorpyrifos, p,p’-DDD and p,p’-DDT and the metabolite p,p’-DDE.

Solid phase microextraction and gas chromatography coupled to magnetic sector high resolution mass spectrometry for the ultra-trace determination of contaminants in surface water

With the aim of monitoring water quality according to the regulations established by the European Union it would be necessary to implement analytical methodologies capable of simultaneously determining a broad range of organic pollutants at ultra-trace levels, allowing for increased sample throughput. In addition, the high number of samples to be analyzed requires a particular focus on setting up fully automated analytical methodologies. In view of that, this study is aimed at the development of a complete automated procedure for the ultra-trace determination of certain pesticides, polycyclic aromatic hydrocarbons (PAHs), brominated diphenyl ethers (BDEs) and polychlorinated biphenyls (PCBs) in surface waters. The proposed method is based on an on-line combination of solid phase microextraction (SPME) and gas chromatography coupled to double-focusing magnetic sector high resolution mass spectrometry (GC–HRMS). SPME as well as GC–HRMS conditions were optimized to achieve maximum extraction efficiency and sensitivity, which was reinforced by using multiple ion detection (MID) as acquisition mode. Using only 19mL of water and with minimum sample manipulation, the method allowed for the determination of 53 compounds exhibiting good linearity (R2>0.99), recoveries between 84 and 118% and relative standard deviation (RSD) values <20% for intra-day and inter-day precision. In addition, the method provides quantification limits (LOQs) between 0.1–50ngL−1, lower than the Environmental Quality Standards (EQS) fixed by Directive 2013/39/EC. Finally, the method was successfully applied to determine target contaminants in Almería surface water compartments, detecting dioxin-like PCBs, BDEs and some pesticides.

The performance of atmospheric pressure gas chromatography–tandem mass spectrometry compared to gas chromatography–high resolution mass spectrometry for the analysis of polychlorinated dioxins and polychlorinated biphenyls in food and feed samples

Recently, gas chromatography tandem mass spectrometry (GC–MS/MS) has been added in European Union (EU) legislation as an alternative to magnetic sector high resolution mass spectrometry (HRMS) for the analysis of dioxins and dioxin like polychlorinated biphenyls (dl-PCB) in food and feed. In this study the performance of APGC–MS/MS compared to GC–HRMS is investigated and compared with EU legislation. The study includes the legislative parameters, relative intermediate precision standard deviation (SRw,rel), trueness, sensitivity, linear range and ion ratio tolerance. In addition, over 200 real samples of large variety and spanning several orders of magnitude in concentration were analyzed by both techniques and the selectivity was evaluated by comparing chromatograms. The SRw,rel and trueness were evaluated using (in-house) reference samples and fulfill to EU legislation, though the SRw,rel was better with GC–HRMS. The sensitivity was considerably better than of GC–HRMS while the linear range was similar. Ion ratios were mostly within the tolerable range of ±15%. A (temporary unresolved) systematic deviation in ion ratio was observed for several congeners, yet this did not lead to exceeding of the maximum ion ratio limits. The APGC–MS/MS results for the non-dioxin-like-PCBs (ndl-PCBs) were negatively biased, particularly for PCB138 and 153 in contaminated samples. The selectivity of APGC–MS/MS was lower for several matrices. Particularly for contaminated samples, interfering peaks were observed in the APGC chromatograms of the native compounds (dioxins) and labeled internal standards (PCBs). These can lead to biased results and ultimately to false positive samples. It was concluded that the determination of dioxins and PCBs using APGC–MS/MS meets the requirements set by the European Commission. However, due to generally better selectivity and SRw,rel, GC–HRMS is the preferred method for monitoring purposes.

A novel method for quantification of decabromodiphenyl ether in plastics without sample preparation using direct insertion probe – magnetic sector high resolution mass spectrometry

We report a rapid, efficient analytical method for detecting Brominated Flame Retardants (BFRs) in plastic materials using direct insertion probe with double focusing magnetic sector high resolution mass spectrometry.

Simultaneous determination of three alternative flame retardants (dechlorane plus, 1,2-bis(2,4,6-tribromophenoxy) ethane, and decabromodiphenyl ethane) in soils by gas chromatography–high resolution mass spectrometry

A gas chromatography–high resolution mass spectrometry (GC–HRMS) method has been developed for the simultaneous determination of three alternative flame retardants, dechlorane plus (DP), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), and decabromodiphenyl ethane (DBDPE) in soils. The soil samples were extracted by accelerated solvent extraction, followed by purification with concentrated sulfuric acid partitioning combined with acid–base silica gel column separation. The gas chromatography featured with a thermostable capillary column of short length and a thin stationary phase was operated in pulse injection mode. A double-focusing magnetic sector high resolution mass spectrometer with electron impact ionization was used for quantification of the analytes. The method detection limits were 0.27–0.33pg for DPs, 0.41pg for BTBPE, and 36pg for DBDPE. The mean recoveries for DPs, BTBPE, and DBDPE in spiked soils were 88–107%, 78–97%, and 74–113%, respectively, with relative standard deviations ranging from 5.2% to 18%. The recoveries of 13C-labeled standards for DPs, BTBPE, and DBDPE in soil samples were 45–110%, 67–118%, and 27–82%, respectively. These results met the acceptable range of labeled standards for analysis of polybrominated diphenyl ethers as specified by the USEPA 1614 method.

Simultaneous and highly sensitive determination of PCBs and PBDEs in environmental water and sediments by gas chromatography coupled to high resolution magnetic sector mass spectrometry

Sensitive and simultaneous determination of PCBs and PBDEs in environmental samples (water and sediments) using high resolution magnetic sector mass spectrometry.

Heterogeneous photocatalysis of moxifloxacin: Identification of degradation products and determination of residual antibacterial activity

TiO2-mediated heterogeneous photocatalysis of the fluoroquinolone antibiotic moxifloxacin in water is investigated with respect to both the formation of degradation products and the evaluation of residual antibacterial activity after photocatalytic treatment. High-resolution magnetic sector mass spectrometry coupled to high performance liquid chromatograph is used to determine the accurate mass of the measured degradation products. Eight main photoproducts are identified at both acidic, neutral and alkaline pH. A molecular structure is proposed by using the accurate mass, the double bond equivalent and by taking into account the structural formula of the parent compound. The photocatalytic degradation does not take place at the quinolone core and defluorination was not observed. A general initial photocatalytic pathway for moxifloxacin is proposed. Time profiles of the different degradation products reveal that the solution pH influences their relative abundance during reaction but the observed degradation products show no pH dependency. Residual antibacterial activity of the photocatalytic reaction solutions against Escherichia coli (G−), Staphylococcus carnosus (G+), Streptococcus mutans (G+) and Klebsiella pneumoniae (G−) is evaluated by means of agar diffusion tests. A reduction in antibacterial activity is noticed for all investigated pH levels with a complete inactivation at neutral pH after 12min of photocatalytic treatment.

From multi-residue screening to target analysis of pharmaceuticals in water: Development of a new approach based on magnetic sector mass spectrometry and application in the Nairobi River basin, Kenya

This paper presents the development and application of a new multi-residue analytical method providing the first data on the environmental occurrence of human pharmaceuticals in Africa, particularly the Nairobi River basin (Kenya).Based on pharmaceutical consumption data available for the Nairobi region, 43 ‘priority’ pharmaceutically active ingredients (PAIs) were selected for this study. On the basis of magnetic sector high-resolution mass spectrometry, a new methodology involving both full-scan screening and selective target analysis has been developed to investigate the presence of the defined priority PAIs. Subsequent analysis of the corresponding standard compounds provided the full confirmation and indicative concentrations (low ng/L–high μg/L) of 10 human PAIs in the Nairobi River. The detected compounds belong to different classes, i.e. antibiotics, analgesic/anti-inflammatory and anti-epileptic drugs, antimalarials and antiretrovirals. Ibuprofen, paracetamol, sulfamethoxazole and zidovudine showed to be the most concentrated PAIs (about 10–30μg/L). The concentration of the antiretrovirals (lamivudine, zidovudine and nevirapine) is clearly higher than those reported in the literature, although environmental data on this class of PAIs are still very limited. To the best of our knowledge, this is the first study that provides evidence of detection of lamivudine in surface water. The presented unique data on the occurrence of selected PAIs in the aquatic environment of Africa clearly show that the high prevalence of specific diseases like HIV/AIDS infection in developing countries might result in a different pattern of PAIs in environmental waters compared to the more developed regions.

Cryogenic zone compression for the measurement of dioxins in human serum by isotope dilution at the attogram level using modulated gas chromatography coupled to high resolution magnetic sector mass spectrometry

A liquid nitrogen jet-cooled thermal modulator dedicated to comprehensive two-dimensional gas chromatography has been mounted in a GC oven coupled to a high resolution magnetic sector mass spectrometry instrument. The data acquisition parameters of the slow double-focusing magnetic sector MS instrument have been optimized to accommodate the description of the narrow modulated GC peaks. Acquisition rates were increased to 20 Hz, while maintaining high mass resolution. Selected ion monitoring (SIM) descriptors, typically including several ions for both native and labeled analytes, were thus reduced to one or two to ensure enough MS cycle time. For maximization of the sensitivity enhancement due to cryogenic zone compression (CZC), the entire GC peak of interest was trapped and remobilized in one event. Optimization of the method resulted in the ability to detect low attogram (ag) amounts of 2,3,7,8-tetrachlorodibenzo- p-dioxin (2,3,7,8-TCDD) (313 ag gives a S/N of 400:1), a level that had not yet been attained using classical GC–HRMS. An isotope-dilution calibration curve was constructed using 13C 12-2,3,7,8-TCDD as the internal standard over the range of 500 ag/μL to 35,000 ag/μL ( R 2 = 0.9953). Analyses of a standard natural human reference serum-matrix NIST SRM 1589a containing 223 ag of 1,2,3,7,8-pentachlorodibenzo- p-dioxin (1,2,3,7,8-PeCDD) (70% recovery rate assumed) resulted in a peak with a S/N of 188:1 (4 sigma, m/ z = 355.8546). Measurement of 2,2-bis (4-chlorophenyl-1,1,1-trichloroethane) (DDE) and 2,2′,4,4′,5,5′-hexabromobiphenyl (BB-153) in human dried-blood spot (DBS) samples is also reported to illustrate the usefulness of such a sensitive technique. Finally, some of the challenges related to sample preparation, blank levels, and to the fact of measuring of such a limited number of molecules (less than 600,000 TCDD molecules) are discussed.

Potent Mechanism-based Inhibitors for Matrix Metalloproteinases

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that play important roles in physiological and pathological conditions. Both gelatinases (MMP-2 and -9) and membrane-type 1 MMP (MMP-14) are important targets for inhibition, since their roles in various diseases, including cancer, have been well established. We describe herein a set of mechanism-based inhibitors that show high selectivity to gelatinases and MMP-14 (inhibitor 3) and to only MMP-2 (inhibitors 5 and 7). These molecules bind to the active sites of these enzymes, initiating a slow binding profile for the onset of inhibition, which leads to covalent enzyme modification. The full kinetic analysis for the inhibitors is reported. These are nanomolar inhibitors (Ki) for the formation of the noncovalent enzyme-inhibitor complexes. The onset of slow binding inhibition is rapid (k(on) of 10(2) to 10(4) M(-1) s(-1) and the reversal of the process is slow (k(off) of 10(-3) to 10(-4) s(-1)). However, with the onset of covalent chemistry with the best of these inhibitors (e.g. inhibitor 3), very little recovery of activity (<10%) was seen over 48 h of dialysis. We previously reported that broad spectrum MMP inhibitors like GM6001 enhance MT1-MMP-dependent activation of pro-MMP-2 in the presence of tissue inhibitor of metalloproteinases-2. Herein, we show that inhibitor 3, in contrast to GM6001, had no effect on pro-MMP-2 activation by MT1-MMP. Furthermore, inhibitor 3 reduced tumor cell migration and invasion in vitro. These results show that these new inhibitors are promising candidates for selective inhibition of MMPs in animal models of relevant human diseases.

Using a high-resolution magnetic sector mass spectrometer for fast analysis of transient reaction processes in automotive catalytic converters.

A high-resolution magnetic sector mass spectrometer has been developed and used for transient kinetic measurements on reactions that are important for automotive exhaust gas catalysis. This instrument allows separation of the isobaric masses of CO and N2 as well as CO2 and N2O, which are separately monitored in time at a sampling rate of 48 Hz. The time resolution is sufficient to determine individual kinetic rate parameters for reactions under transient conditions. A description of the experimental set-up as well as the software used is given. The results are illustrated by the catalytic reduction of NO by CO. To the best knowledge of the authors, this is the first application of a magnetic sector mass spectrometer for kinetic research under dynamic operation conditions.

NO reduction by CO over automotive exhaust gas catalysts in the presence of O2

The reduction of NO by CO in absence and presence of O2 has been investigated by transient experiments at automotive cold-start conditions over Pt/Rh/CeO2/γ-Al2O3, and derived model catalysts. A high-resolution magnetic sector mass spectrometer was used for distinguishing CO/N2 and CO2/N2O. Mechanistic comparisons are made between the catalyst formulations. A kinetic scheme of elementary reaction steps is proposed, which highlights the various contributions of the catalyst constituents.

Design and performance of a high resolution electrospray ion source for a magnetic sector mass spectrometer with a heated capillary inlet

The design and performance of an electrospray ion source for a high resolution magnetic sector mass spectrometer that utilizes a heated capillary has been presented. Low pressure, high sensitivity, stable electrospray, low flow rates, and low electronic noise were important factors in achieving high resolution electrospray mass spectrometry. A unit mass resolution has been achieved for biomolecules with MW > 12,000, and an accuracy of 1.4 ppm has been achieved for the average molecular weight of bovine insulin.

Determination of metabolites of a novel platinum anticancer drug JM216 in human plasma ultrafiltrates

The present study describes the application of on-line liquid chromatography-electrospray ionisation in conjunction with a high resolution magnetic sector mass spectrometer to identify metabolites of a platinum(IV) anticancer drug JM216 bis(acetato)amminedichloro(cyclohexylamine)platinum(IV)] in human plasma. Four metabolites were identified following incubation of JM216 in human plasma: JM118 [amminedichlorocyclohexylamineplatinum(II)], a platinum(II) complex; JM383 [bis(acetato)amminedihydroxo(cyclohexylamine)platinum(IV)]; JM518 [bis(acetato)amminechloro(cyclohexylamine)hydroxoplatinum(IV)] and its isomer JM559. The platinum complexes mass spectra were dominated by the natriated [M + Na] + ion. Elemental compositions of these natriated ions were confirmed by accurate mass measurement on a magnetic sector mass spectrometer in the course of LC/MS analysis. This study demonstrates the capability of direct LC-ESI/MS with accurate mass measurement for analysis of platinum complexes in biological samples. Our results suggest that LC-ESI/MS is a powerful technique for structure elucidation of novel metabolites, and could make valuable contributions to drug metabolism research.

New high-resolution inductively coupled plasma mass spectrometry technology applied for the determination of V, Fe, Cu, Zn and Ag in human serum

Spectral interferences are a limiting factor in quadrupole inductively coupled plasma mass spectrometry (quadropole ICP-MS). Most of these interferences disappear when a high-resolution magnetic sector mass spectrometer is coupled to the ICP ion source. In this paper, results of the first analyses with a new type of a high resolution ICP-MS instrument are shown. The instrument is a commercially available machine (Finnigan MAT, Bremen, Germany) offering standard resolution settings of 300, 3000 and 7000 (M/ΔM, 10% valley definition). With a resolution setting of 3000, V, Fe, Cu and Zn were determined in a second generation human serum reference material. Human serum diluted 4- to 8-fold was measured. The results, expressed as concentrations (µg g–1)[standard deviation (SD) in parentheses] in the freeze dried material for Fe, 23.6 (0.8); Cu, 10.7 (0.2); and Zn, 8.2 (0.8) are in good agreement with the certified values. The very low V content is not certified. In the high-resolution spectrum the V peak was measured next to an approximately 1000 times higher 35Cl16O peak and a concentration of 0.83 ng g–1, SD 0.09 ng g–1 was found, which confirms an earlier radiochemical neutron activation value of 0.67 ng g–1, SD 0.05 ng g–1. For the determination of Ag using the low resolution (300) setting a limit of detection (LOD) of 4.3 pg ml–1 in the solution was found. The instrumental LOD is 10–100 times lower and the experiments show that an investigation of blanks and methods of dealing with memory effects will be necessary before full use can be made of the sensitivity of high resolution ICP-MS.