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.     

Recent applications of gas chromatography with high‐resolution mass spectrometry

Gas chromatography coupled to high‐resolution mass spectrometry is a powerful analytical method that combines excellent separation power of gas chromatography with improved identification based on an accurate mass measurement. These features designate gas chromatography with high‐resolution mass spectrometry as the first choice for identification and structure elucidation of unknown volatile and semi‐volatile organic compounds. Gas chromatography with high‐resolution mass spectrometry quantitative analyses was previously focused on the determination of dioxins and related compounds using magnetic sector type analyzers, a standing requirement of many international standards. The introduction of a quadrupole high‐resolution time‐of‐flight mass analyzer broadened interest in this method and novel applications were developed, especially for multi‐target screening purposes. This review is focused on the development and the most interesting applications of gas chromatography coupled to high‐resolution mass spectrometry towards analysis of environmental matrices, biological fluids, and food safety since 2010. The main attention is paid to various approaches and applications of gas chromatography coupled to high‐resolution mass spectrometry for non‐target screening to identify contaminants and to characterize the chemical composition of environmental, food, and biological samples. The most interesting quantitative applications, where a significant contribution of gas chromatography with high‐resolution mass spectrometry over the currently used methods is expected, will be discussed as well.     

Analysis of brominated dioxins and furans by high resolution gas chromatography/high resolution mass spectrometry

This article reviews the available literature on the analysis of brominated dibenzo-p dioxins and furans (PBDD/Fs) by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). Sample extraction and clean up, injection techniques, chromatographic separation, labelled standards and QA/QC works are discussed. Furthermore, full separation of PBDD/Fs from polybrominated diphenyl ethers (PBDEs) during clean up and control of possible chromatographic interference of PBDEs during instrumental analysis as well as possible actions to further enhance the quality of published data are discussed in detail.     

Review of the Sampling and Pretreatment Methods for Dioxins Determination in Solids,Liquids and Gases

The analytical requirements for the determination of dioxins (e.g. PCDD, PCDF) are unique in comparison with those for other routinely monitored chemicals: dioxins are measured in parts per trillion (ppt) and lower levels in technical and environmental samples, whereas other organics are measured in parts per million (ppm) or parts per billion (ppb). The ultra‐trace analysis of dioxins requires a high sample enrichment obtainable by the use of efficient extraction methods and highly selective purification/fractionation techniques. Furthermore, highly sensitive equipment (e.g. high resolution gas chromatography ‐ HRGC) with detection levels in the ppt range must be used to isolate and separate a huge number of dioxin congeners. The quantification of the dioxins by a high resolution mass detector (HRMS) requires the use of internal and labeled standards. This paper reviews and compares the classic and modern pretreatment methods, namely extraction and clean‐up, that are currently used in dioxin analysis in industrial samples and that were improved or developed in the last 25 years. In addition, the standard methods for dioxin sampling from an emission source (flue or stack gas) are examined and compared with new, automated techniques.     

Recent advances in mass spectrometric measurement of dioxins

Past years, many efforts have been dedicated to the development of alternative analytical methods for the measurement of dioxins in various types of matrices. Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are compounds that are present in samples at part-per-billion (ppb) or part-per-trillion (ppt) level. Their measurement requires the use of very sensitive analytical methods. Gas chromatography (GC) coupled to quadrupole ion storage mass spectrometry (QISTMS), fast GC (FGC) coupled to time-of-flight mass spectrometry (TOFMS) and comprehensive two-dimensional gas chromatography (GC x GC) coupled to TOFMS are the more promising tools challenging the reference GC high resolution mass spectrometry (HRMS) based on sector instruments. We report herein some of the advances we achieved in the past years in our laboratory on the development of alternative measurement methods for those compounds.     

生物样品二恶英分析中两个常见干扰峰的鉴定

利用高分辨气相色谱/高分辨质谱联用仪（HRGC/HRMS）和高分辨气相色谱/低分辨质谱仪（HRGC/LRMS）对实际生物样品中二恶英（polychlorinated dibenzo-p-dioxins and dibenzofurans,PCDD/Fs）的分析过程中¹³C标记的2,3,7,8-四氯代二苯并呋喃（¹³C₁₂-2,3,7,8-TCDF）监测碎片离子通道的两个常见干扰峰进行了分析鉴定。通过实际样品分析结果首先推测这两个干扰峰可能为有机氯农药类化合物滴滴涕（DDT）降解产物滴滴伊（DDE）的两个异构体,其次采用DDE的标准溶液（包括o,p’-DDE和p,p’-DDE）进行分析确认。通过HRGC/HRMS的色谱峰分离效果分析、色谱保留时间匹配以及与DDE碎片离子的理论丰度比进行比较,最终确认实际样品分析中的两个干扰峰依次为o,p’-DDE和p,p’-DDE。本文可为生物样品中二恶英的准确识别提供重要参考。     

An overview of the doping control analysis during the Olympic Games of 2004 in Athens, Greece

This study summarizes the results obtained from the doping control analysis during the period of the XXVIII summer Olympic Games (30 July-29 August 2004). The analysis of all doping control samples was performed at the Doping Control Laboratory (DCL)—the World Anti-Doping Agency (WADA) Accredited Laboratory of Athens. Three thousand six hundred and seventeen tests were conducted in total throughout the games. In 23 specimens the presence of a prohibited substance was confirmed. Sixteen of those were related to anabolic agents. The screened results were confirmed with various mass spectrometry analytical techniques, such as gas chromatography/high resolution mass spectrometry (GC/HRMS), gas chromatography/mass spectrometry (GC/MS), gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) and liquid chromatography/mass spectrometry (ion trap) (LC/MS). The results of the first time applied screening and confirmatory procedures for the detection of recombinant human growth hormone in serum were also presented. Besides, 107 therapeutic use exemptions (TUE) were verified for glucocorticosteroid and beta2-agonist use.     

Hair Analysis as Method for Determination of Level of Drugs and Pharmaceutical in Human Body: Review of Chromatographic Procedures

Abstract

Interest in hair analysis as an alternativ or complementary approach to urinalysis for drug abuse detection has grown in recent years. Hair analysis can be particularly advantageous for drugs and their enantiomers.

More than hundred pharmaceuticals, drugs of abuse agents are reported to be detectable in human and animal hair. This article reviews the aalysis of drugs and drug metabolites by chromatographic procedures, incuding the pretreatment steps, and the xtraction methods. Tihe eneral tendency in the last years, to highly sophisticated techiques gas chromatography–mass spectrometry (GC–MS–NCI), high pressure liquid chromatography–mass spectrometry (HPLC–MS), gas chromatography–mass spectrometry–mass spectrometry (GC–MS–MS) well illustrates this constant fight for sensitivity.     

GC‐MS of amaryllidaceous galanthamine‐type alkaloids

Galanthamine‐type alkaloids produced by plants of the Amaryllidaceae family are potent acetylcholinesterase inhibitors. One of them, galanthamine, has been marketed as a hydrobromide salt for the treatment of Alzheimer's disease. In the present work, gas chromatography with electron impact mass spectrometry (GC‐EIMS) fragmentation of 12 reference compounds isolated from various amaryllidaceous plants and identified by spectroscopic methods (1D and 2D nuclear magnetic resonance, circular dichroism, high‐resolution MS (HRMS) and EIMS) was studied by tandem mass spectrometry (GC‐MS/MS) and accurate mass measurements (GC‐HRMS). The studied compounds showed good peak shape and efficient GC separation with a GC‐MS fragmentation pattern similar to that obtained by direct insertion probe. With the exception of galanthamine‐N‐oxide and N‐formylnorgalanthamine, the galanthamine‐type compounds showed abundant [M]^+. and [M‐H]⁺ ions. A typical fragmentation pattern was also observed, depending on the substituents of the skeleton. Based on the fragmentation pathways of reference compounds, three other galanthamine‐type alkaloids, including 3‐O‐(2′‐butenoyl)sanguinine, which possesses a previously unelucidated structure, were identified in Leucojum aestivum ssp. pulchelum, a species endemic to the Balearic islands. GC‐MS can be successfully applied to Amaryllidaceae plant samples in the routine screening for potentially new or known bioactive molecules, chemotaxonomy, biodiversity and identification of impurities in pharmaceutical substances. Copyright © 2012 John Wiley & Sons, Ltd.     

Approaches to dioxin analysis by HRGC-HRMS and hybrid HRGC-MS-MS

A hybrid mass spectrometer with an EBQQ configuration was used to investigate two approaches to trace dioxin analysis: high resolution gas chromatography – high resolution mass spectrometry (HRGC-HRMS) and high resolution gas chromatography – mass spectrometry – mass spectrometry (HRGC-MS-MS). It is shown that selected ion monitoring (SIM) HRGC-HRMS exhibits better selectivity for dioxins separated on a cyanopropyl column than is otherwise obtained under medium resolution mass spectrometry (3,000 resolution), while optimization of conditions for HRGC-MS-MS allowed the observation of 350 femtograms of the highly toxic 2,3,7,8-TCDF at a S/N ratio of 5:1. Both methods were applied to environmental samples with good results.     

Mass spectrometric properties of N‐(2‐methoxybenzyl)‐2‐(2,4,6‐trimethoxyphenyl)ethanamine (2,4,6‐TMPEA‐NBOMe), a new representative of designer drugs of NBOMe series and derivatives thereof

Emergence of new psychoactive substances, hallucinogenic phenethylamines in particular, in illicit market is a serious threat to human health in global scale. We have detected and identified N‐(2‐methoxybenzyl)‐2‐(2,4,6‐trimethoxyphenyl)ethanamine (2,4,6‐TMPEA‐NBOMe), a new compound in NBOMe series. Identification was achieved by means of gas chromatography/mass spectrometry (GC/MS), including high‐resolution mass spectrometry with tandem experiments (GC/HRMS and GC/HRMS²), ultra‐high performance liquid chromatography/high‐resolution mass spectrometry with tandem experiments (UHPLC/HRMS and UHPLC/HRMS²), and ¹H and ¹³C nuclear magnetic resonance spectroscopy. The peculiarities of fragmentation of the compound under electron ionization (EI) and collision‐induced dissociation were studied. Despite of the empirical rule denying migration of the hydrogen atom in McLafferty rearrangement to the benzene ring with substituents in the both ortho‐positions, it easily occurs for 2,4,6‐TMPEA‐NBOMe in EI conditions. We have noticed that electron‐donating substituents, e.g. methoxy groups in the both ortho‐positions and para‐positions favor the rearrangement. For specially synthesized N‐methyl and N‐acyl derivatives McLafferty rearrangement is not observed. N‐Acyl derivatives demonstrate McLafferty rearrangement, but the charge retains at the alternative fragment involving N‐acyl carbonyl group. We have also showed that the hydrogen atoms in 2,4,6‐trimethoxybenzene ring may be easily substituted for deuterium or for strong electrophiles like trifluoroacetyl. Analytical characteristics of 2,4,6‐TMPEA‐NBOMe and of some derivatives thereof which enable their determination in various criminal seizures are given. Copyright © 2016 John Wiley & Sons, Ltd.     

Analysis of hydroxylated polybrominated diphenyl ether metabolites by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry

Hydroxylated polybrominated diphenyl ether (OH‐PBDEs) metabolites have the potential to cause endocrine disruption as well as other health effects. Currently, gas chromatography/mass spectrometry (GC/MS) after derivatization is used for the analysis of OH‐PBDEs. However, there is a need for the direct analysis of OH‐PBDEs at relatively low concentrations in environmental and biological samples. Liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry (LC/APCI‐MS/MS) was evaluated for the analysis of nine OH‐PBDEs, ranging from tri‐ to hexabrominated. Separation of the nine isomeric metabolites was achieved with reversed‐phase liquid chromatography, followed by detection by APCI‐MS in negative mode. Notably, a significant decrease in ionization was observed in 6‐hydroxyl‐substituted PBDE metabolites in the presence of an ortho‐substituted bromine, relative to the other hydroxylated metabolites. This is probably due to the formation of dioxins in the source as a result of the high‐temperature conditions, which prevented ionization by hydrogen abstraction. The MS/MS experiments also provided evidence of the neutral losses of HBr and Br₂, indicating the possible use of neutral loss scanning and selected reaction monitoring (SRM) for the screening of brominated metabolites in samples. The applicability of LC/APCI‐MS/MS was demonstrated for the analysis of metabolites of BDEs 47 and 99 formed in human liver microsomes. The LC/APCI‐MS/MS method was able to detect metabolites that had previously been identified by GC/MS following derivatization. Copyright © 2010 John Wiley & Sons, Ltd.     

The Chemical Characterization of Potential Organic Interferences in Two Commercially Available Polymeric Adsorbents

Abstract

Current use of synthetic adsorbents for the collection of trace organics in environmental samples is quite extensive. It has been suggested that high levels of organic contaminants in these resins may interfere with subsequent analyses, however, the identity of these suspected contaminants has not been reported.

This paper reports a qualitative and quantitative characterization of the residual organics in two polymeric adsorbents.

Both resins are commercially available polymers of styrene divinyl-benzene. The structures of the contaminants were verified by combined gas chromatography/mass spectrometry (GC/MS). High artifact levels are typical for both of the Amberite® resins studied. The majority of these materials, as verified by capillary GC/MS, were alkyl derivatives of benzene, styrene, naphthalene and biphenyl.     

同位素稀释气相色谱/三重四极杆串联质谱法分析环境样品中的多氯萘

采用稳定同位素标记的多氯萘(PCNs)同类物为内标,建立了同位素稀释气相色谱/三重四极杆串联质谱技术测定环境样品中20种高关注的PCNs同类物的方法。结果表明:PCNs同类物的校正曲线在0.5~200 μg/L范围内线性良好(R²>0.99),检出限(LOD)为0.04~0.48 μg/L,相对标准偏差(RSD)小于15%。采用基质加标法评价该方法对实际环境样品中PCNs测定的回收率为45.2%~87.9%。为验证方法的适用性,以河流沉积物和再生铝冶炼排放的烟道气样品为对象,利用所建立的方法测定了20种PCNs同类物,并将结果与高分辨气相色谱/高分辨质谱方法的测定结果进行了比对,两种方法测定结果的RSD为0.5%~41.4%,表明所建立的同位素稀释气相色谱/三重四极杆串联质谱方法可用于实际环境样品中PCNs的定性、定量分析。     

A Study on Effective Derivatization for Ultra-Micro Detection of Dopamine by Gas Chromatography / Electron Capture Negative Ion Chemical Ionization Mass Spectrometry

Abstract

N-Pentafluorobenzenesulfonyl-O-bis (trimethylsilyl) dopamine was prepared and its properties were discussed for ultra-micro detection of dopamine by gas chromatography / electron capture negative ion chemical ionization mass spectrometry (GC/ECNICIMS). Detection of this derivative was at least 100 times as sensitive by GC/ECNICIMS as by gas chromatography / positive ion chemical ionization mass spectrometry. Deuterium labelled dopamine, dopamine analog phenethylamine and deuterium labelled phenethylamine were also derivatized, respectively, to reveal the fragmentation mechanism of the dopamine derivative. the high sensitivity and speculated fragment ion composition of the derivative by GC/ECNICIMS showed a possibility for highly sensitive detect ion of dopamine.     

Gas Chromatography‐Mass Spectrometry‐Basic Principles,Instrumentation and Selected Applications for Detection of Organic Compounds

Abstract

This mini‐review discusses the analytical technique of gas chromatography‐mass spectrometry (GC‐MS), specifically basic principles and instrumentations. The applications of GC‐MS to a number of studies for determining organic compounds from around the world are presented and highlight its universal use and acceptance. Selected applications show that GC‐MS is an integral and complimentary part of many field studies involving organic compound detection and determination.     

Comparison of sulfo‐conjugated and gluco‐conjugated urinary metabolites for detection of methenolone misuse in doping control by LC‐HRMS,GC‐MS and GC‐HRMS

Methenolone (17β‐hydroxy‐1‐methyl‐5α‐androst‐1‐en‐3‐one) misuse in doping control is commonly detected by monitoring the parent molecule and its metabolite (1‐methylene‐5α‐androstan‐3α‐ol‐17‐one) excreted conjugated with glucuronic acid using gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography mass spectrometry (LC‐MS) for the parent molecule, after hydrolysis with β‐glucuronidase. The aim of the present study was the evaluation of the sulfate fraction of methenolone metabolism by LC‐high resolution (HR)MS and the estimation of the long‐term detectability of its sulfate metabolites analyzed by liquid chromatography tandem mass spectrometry (LC‐HRMSMS) compared with the current practice for the detection of methenolone misuse used by the anti‐doping laboratories. Methenolone was administered to two healthy male volunteers, and urine samples were collected up to 12 and 26 days, respectively. Ethyl acetate extraction at weak alkaline pH was performed and then the sulfate conjugates were analyzed by LC‐HRMS using electrospray ionization in negative mode searching for [M‐H]^? ions corresponding to potential sulfate structures (comprising structure alterations such as hydroxylations, oxidations, reductions and combinations of them). Eight sulfate metabolites were finally detected, but four of them were considered important as the most abundant and long term detectable. LC clean up followed by solvolysis and GC/MS analysis of trimethylsilylated (TMS) derivatives reveal that the sulfate analogs of methenolone as well as of 1‐methylene‐5α‐androstan‐3α‐ol‐17‐one, 3z‐hydroxy‐1β‐methyl‐5α‐androstan‐17‐one and 16β‐hydroxy‐1‐methyl‐5α‐androst‐1‐ene‐3,17‐dione were the major metabolites in the sulfate fraction. The results of the present study also document for the first time the methenolone sulfate as well as the 3z‐hydroxy‐1β‐methyl‐5α‐androstan‐17‐one sulfate as metabolites of methenolone in human urine. The time window for the detectability of methenolone sulfate metabolites by LC‐HRMS is comparable with that of their hydrolyzed glucuronide analogs analyzed by GC‐MS. The results of the study demonstrate the importance of sulfation as a phase II metabolic pathway for methenolone metabolism, proposing four metabolites as significant components of the sulfate fraction. Copyright © 2015 John Wiley & Sons, Ltd.     

Determination of polybrominated biphenyls in Tasmanian devils (Sarcophilus harrisii) by gas chromatography coupled to electron capture negative ion tandem mass spectrometry or electron ionization high‐resolution mass spectrometry

Two gas chromatography/mass spectrometry (GC/MS) methods for the determination of polybrominated biphenyls (PBBs) by isotope dilution analysis (IDA) using ¹³C₁₂‐PBB 153 in the presence of polybrominated diphenyl ethers (PBDEs) were compared. Recovery of ¹³C₁₂‐PBB 153 which was added to the extracted lipids before sample purification was commenced ranged from 88–117% (mean value 98.2 ± 8.9%). Nevertheless, IDA analysis of PBBs using ¹³C₁₂‐labelled congeners is limited by the potential co‐elution of PBBs with polybrominated diphenyl ethers (PBDEs). The pair PBB 153 and BDE 154 was inspected since M⁺ and [M–2Br]⁺ ions of ¹³C₁₂‐PBB 153 and BDE 154 were only separated by 4 u. Gas chromatography/electron ionization high‐resolution mass spectrometry with selected ion monitoring (GC/EI‐HRMS‐SIM) was suitable when m/z 475.7449 and m/z 477.7429 were used for ¹³C₁₂‐PBB 153 because they are below the monoisotopic peak of the [M–2Br]⁺ fragment ion of hexaBDEs at m/z 479.7. Gas chromatography/electron capture negative ion tandem mass spectrometry selected reaction monitoring (GC/ECNI‐MS/MS‐SRM) measurements could be applied because ¹³C₁₂‐PBB 153 and BDE 154 were separated by GC on a 25‐m Factor Four CP‐Sil 8MS column. Comparative measurements with GC/EI‐HRMS‐SIM and GC/ECNI‐MSMS‐SRM were carried out with samples of Tasmanian devils from Tasmania (Australia), an endangered species due to a virus epidemy which has already proved fatal for half of the population. Both techniques verified concentrations of PBB 153 in the range 0.3–11 ng/g lipids with excellent agreement of the levels in all but two samples. The PBB residue pattern demonstrated that PBB pollution originated from the previous discharge with technical hexabromobiphenyl which is dominated by PBB 153. Other congeners such as PBB 132 and PBB 138 were detected in the Tasmanian devils but the proportions relative to PBB 153 were lower than in the technical product. Samples of healthy and affected Tasmanian devils showed no significant difference in the PBB pollution level. The PBB concentrations in the Tasmanian devils were significantly below those causing toxic effects. On the other hand, PBB concentrations were one level or even higher than PBDEs. Copyright © 2008 John Wiley & Sons, Ltd.     

Analysis of [U‐13C6]glucose in human plasma using liquid chromatography/isotope ratio mass spectrometry compared with two other mass spectrometry techniques

The use of stable isotope labelled glucose provides insight into glucose metabolism. The ¹³C‐isotopic enrichment of glucose is usually measured by gas chromatography/mass spectrometry (GC/MS) or gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). However, in both techniques the samples must be derivatized prior to analysis, which makes sample preparation more labour‐intensive and increases the uncertainty of the measured isotopic composition. A novel method for the determination of isotopic enrichment of glucose in human plasma using liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) has been developed. Using this technique, for which hardly any sample preparation is needed, we showed that both the enrichment and the concentration could be measured with very high precision using only 20 µL of plasma. In addition, a comparison with GC/MS and GC/IRMS showed that the best performance was achieved with the LC/IRMS method making it the method of choice for the measurement of ¹³C‐isotopic enrichment in plasma samples. Copyright © 2009 John Wiley & Sons, Ltd.