Summary of LC-HRMS condition for AF determination.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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Rada",authors:[{id:"114650",title:"Dr",name:"Eugen",middleName:null,surname:"Culea",fullName:"Eugen Culea",slug:"eugen-culea"},{id:"114653",title:"Dr.",name:"Simona",middleName:null,surname:"Rada",fullName:"Simona Rada",slug:"simona-rada"}]},{id:"36169",title:"Water in Rocks and Minerals - Species, Distributions, and Temperature Dependences",slug:"water-in-rocks-and-minerals-species-distributions-and-temperature-dependences",signatures:"Jun-ichi Fukuda",authors:[{id:"105384",title:"Dr.",name:"Jun-Ichi",middleName:null,surname:"Fukuda",fullName:"Jun-Ichi Fukuda",slug:"jun-ichi-fukuda"}]},{id:"36170",title:"Attenuated Total Reflection - Infrared Spectroscopy Applied to the Study of Mineral - Aqueous Electrolyte Solution Interfaces: A General Overview and a Case Study",slug:"attenuated-total-reflection-infrared-spectroscopy-applied-to-the-study-of-mineral-aqueous-el",signatures:"Grégory Lefèvre, Tajana Preočanin and Johannes Lützenkirchen",authors:[{id:"108416",title:"Dr.",name:"Johannes",middleName:null,surname:"Lützenkirchen",fullName:"Johannes Lützenkirchen",slug:"johannes-lutzenkirchen"},{id:"111675",title:"Dr.",name:"Gregory",middleName:null,surname:"Lefevre",fullName:"Gregory Lefevre",slug:"gregory-lefevre"},{id:"111676",title:"Prof.",name:"Tajana",middleName:null,surname:"Preocanin",fullName:"Tajana Preocanin",slug:"tajana-preocanin"}]},{id:"36171",title:"Research of Calcium Phosphates Using Fourier Transform Infrared Spectroscopy",slug:"research-of-calcium-phosphates-using-fourier-transformation-infrared-spectroscopy",signatures:"Liga Berzina-Cimdina and Natalija Borodajenko",authors:[{id:"110522",title:"Prof.",name:"Liga",middleName:null,surname:"Berzina-Cimdina",fullName:"Liga Berzina-Cimdina",slug:"liga-berzina-cimdina"},{id:"112181",title:"MSc.",name:"Natalija",middleName:null,surname:"Borodajenko",fullName:"Natalija Borodajenko",slug:"natalija-borodajenko"}]},{id:"36172",title:"FTIR Spectroscopy of Adsorbed Probe Molecules for Analyzing the Surface Properties of Supported Pt (Pd) Catalysts",slug:"ftir-spectroscopy-of-adsorbed-probe-molecules-for-analyzing-the-surface-properties-of-supported-pt-p",signatures:"Olga B. Belskaya, Irina G. Danilova, Maxim O. Kazakov, Roman M. Mironenko, Alexander V. Lavrenov and Vladimir A. 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Cabanelas",slug:"juan-c.-cabanelas"}]},{id:"36179",title:"Use of FTIR Analysis to Control the Self-Healing Functionality of Epoxy Resins",slug:"use-of-ft-ir-analysis-to-control-the-self-healing-functionality-of-epoxy-resins",signatures:"Liberata Guadagno and Marialuigia Raimondo",authors:[{id:"106836",title:"Prof.",name:"Liberata",middleName:null,surname:"Guadagno",fullName:"Liberata Guadagno",slug:"liberata-guadagno"}]},{id:"36180",title:"Infrared Analysis of Electrostatic Layer-By-Layer Polymer Membranes Having Characteristics of Heavy Metal Ion Desalination",slug:"infrared-analysis-of-electrostatic-layer-by-layer-polymer-membranes-having-characteristics-of-heavy",signatures:"Weimin Zhou, Huitan Fu and Takaomi Kobayashi",authors:[{id:"110384",title:"Dr.",name:"Takaomi",middleName:null,surname:"Kobayashi",fullName:"Takaomi Kobayashi",slug:"takaomi-kobayashi"}]},{id:"36181",title:"Infrared Spectroscopy as a Tool to Monitor Radiation Curing",slug:"infrared-spectroscopy-as-a-tool-to-monitor-radiation-curing",signatures:"Marco Sangermano, Patrick Meier and Spiros Tzavalas",authors:[{id:"112286",title:"Dr.",name:"Spiros",middleName:null,surname:"Tzavalas",fullName:"Spiros Tzavalas",slug:"spiros-tzavalas"},{id:"114382",title:"Prof.",name:"Marco",middleName:null,surname:"Sangermano",fullName:"Marco Sangermano",slug:"marco-sangermano"},{id:"114384",title:"Dr",name:"Patrick",middleName:null,surname:"Meier",fullName:"Patrick Meier",slug:"patrick-meier"}]},{id:"36182",title:"Characterization of Compositional Gradient Structure of Polymeric Materials by FTIR Technology",slug:"characterization-of-compositional-gradient-structure-of-polymeric-materials-by-ft-ir-technology",signatures:"Alata Hexig and Bayar Hexig",authors:[{id:"20867",title:"Dr.",name:"Bayar",middleName:null,surname:"Hexig",fullName:"Bayar Hexig",slug:"bayar-hexig"},{id:"111986",title:"Dr.",name:"Alata",middleName:null,surname:"Hexig",fullName:"Alata Hexig",slug:"alata-hexig"}]},{id:"36183",title:"Fourier Transform Infrared Spectroscopy - Useful Analytical Tool for Non-Destructive Analysis",slug:"fourier-trasform-infrared-spectroscopy-useful-analytical-tool-for-non-destructive-analysis",signatures:"Simona-Carmen Litescu, Eugenia D. Teodor, Georgiana-Ileana Truica, Andreia Tache and Gabriel-Lucian Radu",authors:[{id:"24425",title:"Dr.",name:"Simona Carmen",middleName:null,surname:"Litescu",fullName:"Simona Carmen Litescu",slug:"simona-carmen-litescu"},{id:"24429",title:"Prof.",name:"Gabriel-Lucian",middleName:null,surname:"Radu",fullName:"Gabriel-Lucian Radu",slug:"gabriel-lucian-radu"},{id:"108318",title:"Dr.",name:"Eugenia D.",middleName:null,surname:"Teodor",fullName:"Eugenia D. Teodor",slug:"eugenia-d.-teodor"},{id:"108323",title:"Dr.",name:"Georgiana-Ileana",middleName:null,surname:"Badea",fullName:"Georgiana-Ileana Badea",slug:"georgiana-ileana-badea"},{id:"136337",title:"Ms.",name:"Andreia",middleName:null,surname:"Tache",fullName:"Andreia Tache",slug:"andreia-tache"}]},{id:"36184",title:"Infrared Spectroscopy in the Analysis of Building and Construction Materials",slug:"infrared-spectroscopy-of-cementitious-materials",signatures:"Lucia Fernández-Carrasco, D. Torrens-Martín, L.M. Morales and Sagrario Martínez-Ramírez",authors:[{id:"107401",title:"Dr.",name:"Lucia J",middleName:null,surname:"Fernández",fullName:"Lucia J Fernández",slug:"lucia-j-fernandez"}]},{id:"36185",title:"Infrared Spectroscopy Techniques in the Characterization of SOFC Functional Ceramics",slug:"infrared-spectroscopy-techniques-in-the-characterization-of-sofc-functional-ceramics",signatures:"Daniel A. Macedo, Moisés R. Cesário, Graziele L. Souza, Beatriz Cela, Carlos A. Paskocimas, Antonio E. Martinelli, Dulce M. A. Melo and Rubens M. Nascimento",authors:[{id:"102015",title:"MSc.",name:"Daniel",middleName:null,surname:"Macedo",fullName:"Daniel Macedo",slug:"daniel-macedo"},{id:"112309",title:"MSc",name:"Moisés",middleName:"Romolos",surname:"Cesário",fullName:"Moisés Cesário",slug:"moises-cesario"},{id:"112310",title:"Ms.",name:"Graziele",middleName:null,surname:"Souza",fullName:"Graziele Souza",slug:"graziele-souza"},{id:"112311",title:"MSc.",name:"Beatriz",middleName:null,surname:"Cela",fullName:"Beatriz Cela",slug:"beatriz-cela"},{id:"112312",title:"Prof.",name:"Carlos",middleName:null,surname:"Paskocimas",fullName:"Carlos Paskocimas",slug:"carlos-paskocimas"},{id:"112314",title:"Prof.",name:"Antonio",middleName:null,surname:"Martinelli",fullName:"Antonio Martinelli",slug:"antonio-martinelli"},{id:"112315",title:"Prof.",name:"Dulce",middleName:null,surname:"Melo",fullName:"Dulce Melo",slug:"dulce-melo"},{id:"112316",title:"Dr.",name:"Rubens",middleName:"Maribondo Do",surname:"Nascimento",fullName:"Rubens Nascimento",slug:"rubens-nascimento"}]},{id:"36186",title:"Infrared Spectroscopy of Functionalized Magnetic Nanoparticles",slug:"infrared-spectroscopy-of-functionalized-magnetic-nanoparticles",signatures:"Perla E. García Casillas, Claudia A. Rodriguez Gonzalez and Carlos A. Martínez Pérez",authors:[{id:"104636",title:"Dr.",name:"Perla E.",middleName:null,surname:"García Casillas",fullName:"Perla E. García Casillas",slug:"perla-e.-garcia-casillas"},{id:"112440",title:"Dr.",name:"Carlos A.",middleName:null,surname:"Martínez Pérez",fullName:"Carlos A. Martínez Pérez",slug:"carlos-a.-martinez-perez"},{id:"112441",title:"Dr.",name:"Claudia A.",middleName:null,surname:"Rodriguez Gonzalez",fullName:"Claudia A. Rodriguez Gonzalez",slug:"claudia-a.-rodriguez-gonzalez"}]},{id:"36187",title:"Determination of Adsorption Characteristics of Volatile Organic Compounds Using Gas Phase FTIR Spectroscopy Flow Analysis",slug:"determination-of-adsorption-characteristics-of-volatile-organic-compounds-using-gas-phase-ftir-spect",signatures:"Tarik Chafik",authors:[{id:"107310",title:"Prof.",name:"Tarik",middleName:null,surname:"Chafik",fullName:"Tarik Chafik",slug:"tarik-chafik"}]},{id:"36188",title:"Identification of Rocket Motor Characteristics from Infrared Emission Spectra",slug:"identification-of-rocket-motor-characteristics-from-infrared-emission-spectra",signatures:"N. Hamp, J.H. Knoetze, C. Aldrich and C. Marais",authors:[{id:"112229",title:"Prof.",name:"Chris",middleName:null,surname:"Aldrich",fullName:"Chris Aldrich",slug:"chris-aldrich"},{id:"112232",title:"Prof.",name:"Hansie",middleName:null,surname:"Knoetze",fullName:"Hansie Knoetze",slug:"hansie-knoetze"},{id:"135327",title:"Ms.",name:"Corne",middleName:null,surname:"Marais",fullName:"Corne Marais",slug:"corne-marais"}]},{id:"36189",title:"Optical Technologies for Determination of Pesticide Residue",slug:"optical-technology-for-determination-of-pesticide-residue",signatures:"Yankun Peng, Yongyu Li and Jingjing Chen",authors:[{id:"113343",title:"Prof.",name:"Yankun",middleName:null,surname:"Peng",fullName:"Yankun Peng",slug:"yankun-peng"},{id:"116636",title:"Dr.",name:"Yongyu",middleName:null,surname:"Li",fullName:"Yongyu Li",slug:"yongyu-li"},{id:"116637",title:"Dr.",name:"Jingjing",middleName:null,surname:"Chen",fullName:"Jingjing Chen",slug:"jingjing-chen"}]},{id:"36190",title:"High Resolution Far Infrared Spectra of the Semiconductor Alloys Obtained Using the Synchrotron Radiation as Source",slug:"high-resolution-spectra-of-semiconductor-s-alloys-obtained-using-the-far-infrared-synchrotron-radi",signatures:"E.M. Sheregii",authors:[{id:"102655",title:"Prof.",name:"Eugen",middleName:null,surname:"Sheregii",fullName:"Eugen Sheregii",slug:"eugen-sheregii"}]},{id:"36191",title:"Effective Reaction Monitoring of Intermediates by ATR-IR Spectroscopy Utilizing Fibre Optic Probes",slug:"effective-reaction-monitoring-of-intermediates-by-atr-ir-spectroscopy-utilizing-fibre-optic-probes",signatures:"Daniel Lumpi and Christian Braunshier",authors:[{id:"109019",title:"Dr.",name:"Christian",middleName:null,surname:"Braunshier",fullName:"Christian Braunshier",slug:"christian-braunshier"},{id:"111798",title:"MSc.",name:"Daniel",middleName:null,surname:"Lumpi",fullName:"Daniel Lumpi",slug:"daniel-lumpi"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"75992",title:"Determination of Aflatoxins by Liquid Chromatography Coupled to High-Resolution Mass Spectrometry",doi:"10.5772/intechopen.96790",slug:"determination-of-aflatoxins-by-liquid-chromatography-coupled-to-high-resolution-mass-spectrometry",body:'Aflatoxins (AFs) are highly toxic secondary metabolites produced by fungi belonging to several
Chemical structure of the most important AFs and their derivatives.
Raw materials usually used for human food and animal feed are contaminated by this type of fungi and their metabolites. Cereals (maize, wheat, rice, barley, soy, etc.), dried fruits, nuts, coffee and other foods could be contaminated during plant growth or postharvest, depending on different factors such as temperature, humidity, water activity, concurrent mycobiota, physical damage, and other storage conditions [2]. AFs are very stable and may resist cooking processes, resulting a problem in processed foods. Human exposure to AFs can result directly from ingestion of contaminated foods, or indirectly from consumption of animal foods previously exposed to contaminated feeds. AFs have a great risk for human health, especially by their carcinogenic potential [3]. Degradation or enzymatic transformation of mycotoxins led to the appearance of modified mycotoxins, usually lesser toxic than the parent compounds. Thus, aflatoxin M1 (AFM1) is formed from the hydroxylation of AFB1 and eliminated in the milk of animals that consumed feed contaminated with this mycotoxin [4].
Therefore, it is important to develop reliable methods for the determination of AFs and their derivatives in foods and feeds, as well as toxicokinetic and toxicodynamic studies for assessment of human or animal exposure. The target and non-target qualitative and quantitative analysis using high resolution mass spectrometry (HRMS) instruments, such as time-of-flight (TOF) and Orbitrap, brings great challenges for screening of AFs [5]. Main advantages include high sensitivity, accurate mass measurement, and retrospective data analysis, allowing both the target determination of AFs and the non-targeted screening of modified AFs or unknown metabolites.
AFs are potent carcinogenic, mutagenic, teratogenic, and immunosuppressive agents. Their carcinogenicity has mainly been associated with liver and kidney, although the effect of AFs has also been reported in pancreas, bladder, bone, viscera or central nervous by some epidemiological and animal studies [6]. Their inhalation and direct contact could also cause lung and skin [7, 8] occupational cancers, respectively. In addition, feeds contaminated by AFs can involve high susceptibility to diseases, low productivity and low reproductive performance in animals [9].
Among AFs, AFB1 is considered the highest risk. The Scientific Committee on Food has established that AFs are genotoxic carcinogens [10, 11], being the order of toxicity as follows: AFB1 > AFG1 > AFB2 > AFG2. Indeed, AFB1 has been shown to be carcinogenic in all experimental animals and has been classified since 1988 by the World Health Organization (WHO) as a human carcinogen. Consequently, the International Agency for Research on Cancer (IARC) [12] has classified AFB1 within the category of Group 1 substances based on the existence of sufficient evidence about its carcinogenicity to humans, both alone and in natural mixtures with the other AFs [13, 14].
The most common route of entry of AFs into the human body is the ingestion. In the case of AFB1, the best studied aflatoxin, is absorbed in the gastrointestinal tract, due to its liposolubility, and transported by red blood cells and plasma proteins to the liver. In the liver, it is metabolized producing intermediate metabolites that have been related with the toxic and carcinogenic effects of AFs [15]. Specifically, AFB1 is biotransformed in the liver by microsomal enzymes of the cytochrome superfamily P450. Microsomal biotransformation can result in the hydrolyzation of aflatoxin B1, producing less toxic metabolites such as AFM1, aflatoxin Q1 (AFQ1), aflatoxin P1 (AFP1) and aflatoxin B2a (AFB2a). In addition, AFB1 can produce aflatoxicol (AFL) via NADPH reductase. The formation of these compounds is considered a detoxification process although the protein binding of some of them can lead to additional toxicities [16]. They are excreted in urine and feces, although AFM1 is also commonly detected in breast milk.
The action of CYP450 enzymes can also metabolize AFB1 resulting in the appearance of a reactive intermediate metabolite, AFB1–8,9-epoxide (AFBO), which has two isomers (
The interaction AFB1-DNA causes AFB1-N7-guanine adduct, which is chemically unstable and undergoes rapid urinary excretion resulting in an aputinic (AP) site on the DNA backbone [16]. Alternatively, the adduct AFB-N7-guanine may be stabilized by rearranging to a ring-opened formamidopyramidine structure (AFB1-FAPy) [17]. Both AP and AFB1-FAPy can produce mutagenesis. Figure 2 summarizes the action mechanism of AFB1.
Metabolic pathway of AFB1.
From the action mechanism of AFB1 it can be deduced that AFB1-lys, AFB1-N7-guanine, AFB1-mercapturic acid or the hydroxylated forms (AFM1, AFQ1, AFP1, AFL and AFB2a) could be effective biomarkers for assessing AF exposure.
Due to the high lesions produced by AFs, especially cancer, the European Union has established maximum permitted levels of these contaminants in various foods through Regulation No. 1881/2006 [19]. Specifically, the maximum contents for AFB1, AFB2, AFG1, AFG2 and AFM1 in nuts, cereals, milk and baby foods are included in this regulation the maximum contents are between 4 and 15 μg kg−1.
In the field of animal nutrition, the specifications regarding the presence of mycotoxins in feed are reflected in Directive 2002/32/EC [20]. Only AFB1 has been legislated. The maximum levels ranged between 5 and 50 μg kg−1. The lower limit was set for feed intended for milk-producing animals (5 μg kg−1).
Liquid chromatography (LC)-HRMS is a powerful tool for metabolomic approaches, allowing simultaneous quantitative and qualitative analysis of a wide variety of mycotoxins, as well as the search of related metabolites derived from mycotoxin biotransformation or degradation, enabling the detection and identification of unknown compounds. In addition, HRMS offers the ability to work in various modes, such as target analysis and non-target screening, or retrospective analysis. The relative incompatibility of HRMS ion sources with the continuous liquid flow of LC limited the progress of LC-HRMS coupling for years, but the development of interfaces such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), where LC effluent is de-solvated, has allowed the proposal of a high number of LC-HRMS methods. Thus, complex mixtures can be separated in the chromatographic system and their components are unequivocally detected by HRMS with high sensitivity.
For AFs determination, quadrupole (Q)-TOF, Orbitrap and its hybrid Q-Orbitrap are the mass analysers most widely used. Comparing both instruments, Orbitrap shows better resolution and accuracy (Q-TOF: 60,000 full width at half maximum (FWHM) and between 1 and 10 ppm; Orbitrap: 240,000 FWHM and less than 1 ppm), and a greater range of
ESI or its variant heated ESI (HESI) working in positive mode are the best options for AF determination. Although it should be noted that many of the methods described in this chapter are multiclass methods, i.e., they determine a greater number of mycotoxins, not just AFs, and in this case, authors usually prefer two independent runs using both positive and negative polarities.
Regarding LC instruments, ultra-high-performance LC (UHPLC) is normally coupled to HRMS. Although NanoLC coupled to Q-Orbitrap for the determination of AFB1-lys in human plasma [26] and high performance LC (HPLC)-TOF for the determination of AFB1 in beer [24] have also been proposed. In addition, Qi et al. used a multiple heart-cutting two-dimensional liquid chromatography (Heart-cutting 2D-LC) coupled to Q-Orbitrap for simultaneous determination of AFs and ochratoxin A in snus [27]. The utilization of Heart-cutting 2D-LC enables to reduce matrix effect, leading to better precision of the AF contents. The mobile phase is normally a mixture of water and methanol (MeOH) or acetonitrile (ACN). Formic acid (FA), acetic acid (AA), ammonium formate or ammonium acetate are used as additives. The stationary phase was mainly C18 although C8 has been also proposed [28]. Slobodchikova et al. [22] also used a pentafluorophenyl (PFP) column whereas Qi et al. [27] combined both C18 and PFP columns in the Heart-cutting 2D-LC system.
The analysis of biological samples focused on the monitoring of the four most important AFs (AFB1, AFB2, AFG1 and AFG2), although their adducts due to the interaction of AFB1 with proteins or DNA, AFB1-N7-guanine and AFB1-lys, respectively, as well as its hydrolysed derivative AFM1 have also been determined. In food samples, besides the four main AFs, some metabolites such as AFM1, AFM2, or AFL were also detected.
Both data dependent (dd-MS2) and data independent (DIA) acquisition have been proposed. For the analysis of biological samples, Full MS combined with dd-MS2 by inclusion of a list of accurate masses of target or suspect compounds was more frequent. Although, Ogawa et al. [29] also proposed a dd-MS2 by fixing an ion intensity threshold. Regarding food analysis, authors normally prefer Full MS and DIA, specifically, all-ion fragmentation (AIF) mode, where no precursor ion isolation is carried out. Other modes such as simple Full MS, selected ion monitoring (SIM) or parallel reaction monitoring mode (PRM) have also been investigated. Renaud et al. [30] compared three acquisition modes: dd-MS2 with inclusion list, AIF and AIF using targeted high energy collision dissociation (HCD) events across a mass range for MS/MS. Good linearity was achieved by AIF with different HCD events at low concentrations, demonstrating that the limits of detection (LODs) are much higher without a Q mass filtering. The potential of AIF with different HCD events has also been studied for the determination of five AFs in nutraceutical obtained from green tea [31].
Most authors who carried out a non-targeted acquisition opted for target processing, in order to quantify and/or confirm AFs. Only Jia et al. [31] carried out a non-targeted processing consisting of: non-target fourier peak picking, (ii) spectra automated componentization, (iii) suspicion spectral library searching, and (iv) marked fragments filtering. Finally, compounds were confirmed with reference standard. In addition, Castaldo et al. [32] and Renaud et al. [30] carried out a non-targeted processing using spectral library for the tentative identification of other fungal metabolites, although they processed AFs following a targeted approach.
Table 1 summarizes the separation and detection condition of HRMS methods for AF monitorization.
AFB1, AFB2, AFG1, AFG2, AFM1 | Breast milk | UHPLC–Orbitrap HESI + | Hypersil GOLD C18 (100 × 2.1 mm, 1.9 μm) H2O/MeOH with FA and HCOONH4 | Full MS ( | [33] |
AFB1, AFB2, AFG1, AFG2 | Isoflavone supplements | UHPLC-Orbitrap HESI + | Hypersil Gold C18 (100 × 2.1 mm, 1.9 μm) H2O/MeOH with FA and HCOONH4 | Full MS ( ( | [34] |
AFB1, AFB2, AFG1, AFG2 | Ginkgo biloba supplements | UHPLC-Orbitrap HESI + | Hypersil Gold C18 (100 × 2.1 mm, 1.9 μm) H2O/MeOH with FA and HCOONH4 | Full MS and AIF ( | [35] |
AFB1, AFB2, AFG1, AFG2 | Green tea and royal jelly supplements | UHPLC-Orbitrap HESI + | Hypersil Gold C18 (100 × 2.1 mm, 1.9 μm) H2O/MeOH with FA and HCOONH4 | Full MS and AIF ( | [36] |
AFB1, AFB2, AFG1, AFG2, AFM1, AFL | Coix seed | UHPLC-Orbitrap HESI + | C18 (100 × 2.1 mm, 1.6 μm) H2O/MeOH with FA and CH3COONH4 | Full MS ( | [37] |
AFB1, AFB2, AFG1, AFG2 | Feed | UHPLC-Orbitrap HESI + | Hypersil Gold C18 (100 × 2.1mm,1.9 μm) H2O/MeOH/ACN with AA | Full MS and AIF ( | [38] |
AFB1, AFB1-lys | Human serum | UHPLC-Q-Orbitrap HESI + | C18 (100 × 2.1 mm, 1.7 μm) H2O/MeOH with FA and HCOONH4 | Full MS ( | [39] |
AFB1, AFM1, AFB1-N7-guanine | Human urine | UHPLC-Q-Orbitrap HESI + | Acquity BEH C18 (100 × 2.1 mm, 1.7 μm) H2O/MeOH with FA and HCOONH4 | Full MS (no range) and dd-MS2 (list dependent) | [40] |
AFB1, AFM1 | Milk | UHPLC-Q-Orbitrap HESI + | Luna Omega C18 (50 × 2.1 mm, 1.6 μm) H2O/MeOH with FA and HCOONH4 | Full MS and AIF ( | [41] |
AFB1, AFB2, AFG1, AFG2, AFM1, AFM2 | Milk | UHPLC-Q-Orbitrap HESI + | Accucore C18 (150 x 2.1 mm, 2.6 μm) H2O/ACN with FA and CH3COONH4 | Full MS ( | [42] |
AFB1, AFG1, AFG2 | Maize | UHPLC-Q-Orbitrap HESI + | Zorbax Eclipse Plus RRHD C18 column (50 × 2.1 mm, 1.8 μm) | Full MS, dd-MS2 (list dependent), AIF and AIF with HCD events | [30] |
AFB1, AFB2, AFG1, AFG2 | Cashew nut | UHPLC-Q-Orbitrap HESI + | HSS T3 (100 x 2.1 mm, 1.8 μm) H2O/MeOH with FA and HCOONH4 | PRM | [43] |
AFB1, AFB2, AFG1, AFG2 | Cereals | UHPLC-Q-Orbitrap HESI + | Kinetex C18 (50 × 3 mm, 1.7 μm H2O/MeOH with AA and CH3COONH4 | Full MS and AIF ( | [44] |
AFB1 | Durum wheat pasta and baby food pasta | UHPLC-Q-Orbitrap HESI + | Accucore C18 (100 × 2.1 mm 2.6 μm) H2O/MeOH with FA and HCOONH4 | Full MS ( | [45] |
AFB1, AFB2, AFG1, AFG2, AFM1 | Green tea supplements | UHPLC-Q-Orbitrap HESI + | Hypersil Gold C18 (100 × 2.1 mm, 1.9 μm) H2O/MeOH with FA and HCOONH4 | Full MS ( | [31] |
AFB1, AFB2, AFG1, AFG2 | Medicinal herbs | UHPLC-Q-Orbitrap HESI + | Kinetex C18 column (100 × 2.1 mm, 1.7 μm) H2O/MeOH with FA | SIM | [46] |
AFB1, AFB2, AFG1, AFG2 | Pet foods | UHPLC-Q-Orbitrap HESI + | Luna Omega C18 (50 × 2.1 mm, 1.6 μm) H2O/MeOH with FA and HCOONH4 | Full MS and AIF ( | [32] |
AFB1, AFB2, AFG1, AFG2 | Waters | UHPLC-Q-Orbitrap HESI + | C18 (125 × 2 mm, 5 μm) H2O/ ACN with FA | Full MS (no data) and dd-MS2 (list dependent) | [47] |
AFB1-lys | Human plasma | NanoLC–Q-Orbitrap HESI + | Acclaim C18 (15 cm, 75 μm) H2O/ACN with FA | Full MS ( | [26] |
AFB1, AFB2, AFG1, AFG2 | Snus | Heart-cutting 2D-LC-Q-Orbitrap HESI + | Hypersil Gold C18 (100 × 0.5 mm, 3 μm) and ACQUITY HSS PFP (100 × 2.1 mm, 1.7 μm) H2O/MeOH/ACN with FA and HCOONH4 | PRM | [27] |
AFB1, AFB2, AFG1, AFG2 | Human plasma | UHPLC–IT-Orbitrap HESI + | PFP (50 × 2.1 mm, 2.6 μm) H2O/MeOH with AA | Full MS ( | [22] |
AFB1, AFB2, AFG1, AFG2 | Beer | UHPLC-IT-Orbitrap HESI + | Gemini C18 (150 × 2 mm, 5 μm) H2O/MeOH with FA and HCOONH4 | Full MS ( | [23] |
AFB1 | Beer | HPLC-TOF ESI + | Kinetex C18 (50 × 3 mm, 1.7 μm) H2O/MeOH with FA and CH3COONH4 | Full MS ( | [24] |
AFB1 | Beer | UHPLC-TOF ESI + | Kinetex C18 (50 × 3 mm, 1.7 μm) H2O/ACN with FA and CH3COONH4 | Full MS ( | [25] |
AFB1, AFB2, AFG1, AFG2 | Human plasma | UHPLC–Q-TOF ESI + | ODS C18 (150 × 1.5 mm, 5.0 μm) H2O/MeOH with HCOONH4 | Full MS (no data) and dd-MS2 (Ion intensity-dependent) | [29] |
AFB1-lys | Human serum | UHPLC-Q-TOF ESI + | Acquity BEH C18 (50 × 2.1 mm, 1.7 μm) H2O/ACN with FA | Full MS ( | [48] |
AFB1, AFM1 | Plasma, urine, feces (pig, broiler) | UHPLC-Q-TOF ESI + | Acquity HSS T3 C18 (100 × 2.1 mm, 1.8 μm) H2O/MeOH with FA and HCOONH4 | Full MS and AIF (mass range | [49] |
AFB1 | Seeds, milk, flour, beer | UHPLC-Q-TOF ESI + | Eclipse Plus C8 RRHD (50 × 2.1 mm, 1.8 μm) H2O/ACN with FA | No data | [28] |
AFB1, AFB2, AFG1, AFG2 | Corn | UHPLC-Q-TOF ESI + | Hypersil Gold C18 (100 × 2.1mm, 1.9 μm) H2O/MeOH with FA and CH3COONH4 | Full MS ( | [50] |
Summary of LC-HRMS condition for AF determination.
AFs can grow on many foods, mainly peanuts, maize and cottonseed, although they have also been found in all types of nuts, copra, cereals, sunflower and soya beans, unrefined vegetable oils, spices, dried fruits, coffee, cocoa and animal feed [1, 16].
Because occurrence of mycotoxins in
A simple and rapid multi-mycotoxin method for the determination of 17 mycotoxins simultaneously is described on
Mycotoxins are frequently present in
A
Modern MS detectors can be used not only as detectors, but also as a “separation” tool, due to significant advances in HRMS, achieving greater sensitivity and selectivity. Thus,
Mycotoxins can be present in their parent forms and also in other forms, as
The determination of mycotoxin exposure of human populations is difficult due to the heterogeneous distribution of mycotoxins in foods and the time lag between toxin intake and the development of chronic disease. Therefore, a more reliable and relevant indication of individual exposure could be provided by biomarkers measured in biological fluids.
Aflatoxins can bioaccumulate in the organs and tissues of animals and humans or be excreted by biological fluids or feces [39, 40]. Sensitive analytical procedures are required for the determination of AFs in biological samples due to the very low concentrations involved. Most of the analytical methods proposed are based on LC coupled to different detection systems such as spectrophotometry, fluorescence, MS or MS/MS. Recently, HRMS, including TOF and Orbitrap, resulted an excellent technique for target analysis of AFs as well as for identifying and screening of non-target compounds in metabolomic strategies for studies concerning bioaccumulation, toxicokinetics and excretion of AFs and their metabolites.
Most of the studies are related with
In addition,
In comparison to other biological fluids such as blood, plasma and urine, the database on multi-mycotoxin levels in
Several studies propose to analyze
Figure 3 shows a distribution of the type of food and biological samples for which LC-HRMS methods have been applied in AF determination.
Type of samples more frequently analyzed. The number of published articles dealing with each matrix is indicated.
Method accuracy and precision are strongly conditioned by the effectiveness and robustness of the sample treatment stage. Both physicochemical properties of the AFs and the sample matrix composition need to be considered in the extraction procedure selection, which should ideally isolate and concentrate the analytes, eliminate interferences, and provide extracts compatible with the analytical technique to be used. For example, AFB1 was extracted in acidified ethyl acetate (EtAc) from serum previously submitted to enzymatic digestion (ED) and lipid removing by liquid–liquid extraction (LLE) with hexane. Nevertheless, this extraction medium was unable to isolate the hydrophilic metabolite AFB1-lys from the same sample and, a salting-out step with a quick, easy, cheap, effective, rugged and safe (QuEChERS) mixture was applied [39]. The objective conditions the adoption of a more or less selective sample treatment. Thus, non-selective extractions are applied for non-targeted strategies, allowing retrospective analysis of any potential compound, whereas for targeted analysis, clean and concentrated extracts are required.
Solid samples are generally homogenized by grinding [37, 38, 43, 44, 46], in order to obtain representative sample aliquots before being submitted to a solid–liquid extraction (SLE) stage. Freeze-drying of feces has also been proposed for eliminating any variations due to different moisture contents [49]. For SLE, aqueous mixtures of polar organic solvents such as MeOH, acetone or ACN have been used for AFs isolation from biological [49] and food [37, 43, 44, 46, 52] samples, being the mixtures mechanically shaken. The application of external energy in SLE procedures is sometimes proposed in order to enhance analyte recoveries in low times. Ultrasound assisted extraction (UAE) [30, 32, 50, 55] and microwave assisted extraction (MAE) [28] have efficiently extract AFs from food matrices.
On the other hand, even though food and biological liquid samples could be directly analyzed HRMS or LC combined with HRMS, previous steps are generally applied to minimize matrix effects. Thus, the addition of organic solvents such as ACN or MeOH allowed deproteinization of plasma [26, 29, 49] and milk [42] samples. Enzymatic reactions have also proven to be effective for human serum deproteinization [39, 48].
The removing of non-polar sample components, such as phospholipids, has been proposed by LLE with hexane [39, 46], by solid-phase extraction (SPE) using SPE-phospholipid cartridges for pig feces [49] and well-plates for chicken plasma [49].
The isolation of AFB1, AFB2, AFG1, AFG2 and AFM1 by LLE using EtAc has been applied for urine [49] and serum [22, 39], being recommended though a three-step LLE by Slobodchikova et al. [22] which resulted in better recoveries than those provided by SPE or protein precipitation (PP) procedures in a multi-mycotoxin method.
The simultaneous sample matrix purification and AF isolation is accomplished by many of the applied treatments in a single step. Thus, an on-line SPE device allowed the simultaneous isolation of 12 mycotoxins, including AFB1, and matrix purification of beer samples. Although SPE is more commonly applied under off- line mode, as used by Rubert et al. for isolation of AFB1, AFB2, AFG1, AFG2 in a multi-mycotoxin method proposed for beer [23]. SLE extracts obtained from solid food matrices have also been submitted to SPE [43, 44]. Polymeric sorbents are used in SPE isolation of AFs in their free forms. Whereas mixed-mode SPE-sorbents are selected for the retention of AFB1-lys adduct. Thus, a modified extraction procedure involving a PP step before enzymatic digestion (ED) with Pronase® and SPE-clean-up using strong ion mixed-mode-SPE has allowed both metabolic profiling and AFB1-lys adduct quantification in serum samples [26, 48].
Specific antibody-analyte binding is exploited as clean-up procedure in IACs, reporting interesting applications in AF analysis. Thus, gel suspensions of monoclonal antibody specific for AFs have allowed the purification of AFB1, AFB2, AFG1 and AFG2 from urine [40]. IAC have also been proposed for multi-mycotoxin studies, including AFs, for the analysis of functional and medicinal herbs [46]. In both articles reviewed dealing with IAC, AFs were eluted with MeOH after a washing step for impurities elimination using water [40] of aqueous buffer solutions [46].
QuEChERS methodology has been applied for AFs determination in both food [24, 32, 38, 41, 45, 50, 51, 53, 56] and biological samples [33, 39], using ACN as extractant solvent and a dispersive SPE (DSPE) step with the appropriate sorbents. When QuEChERS clean-up is applied omitting the use of sorbents, so that only implying organic solvent and salts, the procedure is named as simplified QuEChERS, and it has been proposed for isolation of AFB1, AFB2, AFG1, AFG2 and AFM1 from human breast milk [33] and AFB1 from durum wheat pasta [45]. The possibilities of different mixtures of solid sorbents for multi-class determinations of more than 250 compounds, pesticides and mycotoxins, including AFB1, AFB2, AFG1 and AFG2, applied to nutraceutical products have been studied by Martínez-Domínguez et al. [34, 35, 36] and compared with SLE, called in this case as “dilute and shoot” procedure. Best results have been reported by the latter procedure followed by a clean-up step using a mixture of sorbents in a DSPE mode [35, 36] or cartridge packed [34], this clean-up stage applied in order to enhance analyte recoveries and/or maintain the equipment performance for longer periods of times. When “dilute and shoot” procedure was compared to IAC for AFs in urine sample, lower LODs were achieved by the latter, because cleaner extracts with higher AF concentrations were obtained, being therefore selected [40]. An on-line automated sample preparation procedure is developed by Jia et al. [31] for multiple mycotoxin screening in nutraceutical products involving SLE, using aqueous acid solution and ACN, and the obtained supernatant being transferred to a disposable pipette extraction containing salt previously to the application of a clean-up step based on DSPE.
In the last years, nanoparticles (NPs) have received great attention in analytical chemistry due to the high surface area to volume ratio if compared to particles of higher dimensions, thus leading to very efficient extractions in lower times. A mass of 2 mg of zirconia NPs dispersed in the aqueous extract obtained by MAE from food samples allowed the DSPE isolation of AFB1 in 2 min, being then submitted to a desorption step in acidified chloroform [28]. When magnetized NPs are used, the collection of the enriched NPs is easily achieved by applying an external magnetic field, avoiding the centrifugation step. Under this named magnetic dispersive solid-phase extraction (MDSPE) methodology, AFB1, AFB2, AFG1, AFG2, AFM1 and AFM2, in a multiclass mycotoxin analysis method, have been preconcentrated with multi-walled carbon nanotubes (MWCNTs) modified with polyethylene glycol [42]. Although not implying HRMS detection for LC, it is noteworthy that AFB1 has also been preconcentrated with amino-modified magnetic MWCNTs [57].
With the aim to enhance sensitivity and clean-up purposes, the AF extracts finally obtained by applying the selected isolation procedure, are generally evaporated to dryness and reconstituted in low volumes of solvents compatible with the instrumental measurement step.
The data provided in this review demonstrate that most of the studies dealing with AF determination by LC-HRMS are focused on food, feed and biological samples analysis. In fact, only two manuscripts dealing with other matrices, waters [47] and snus [27], were found. A triple-stage SPE, consisting of a hand-made cartridge, packed with porous graphitized carbon and modified styrene-divinylbenzene polymer, coupled to a commercial HLB plus cartridge, allowed the isolation of natural toxins of different polarities. Thus, a screening method is proposed for the tentative identification of mycotoxins, cyanotoxins and plant toxins in surface waters [47]. The use of multiple Heart-cutting 2D-LC-Q-Orbitrap for AF separation and detection, respectively, has probably allowed to apply a very simple procedure in the treatment of snus samples. Thus, LLE in acidified EtAc provided similar analyte recoveries than QuEChERS method [27].
As can be appreciated in Figure 4, sample treatments for AF determination by LC-HRMS have been proposed both applying a unique methodology or through the combination of different procedures generally sequentially applied, for both food and biological samples.
Sample treatments for AF determination by LC-HRMS.
A summary of the sample treatments involved in the reviewed LC-HRMS methods appearing in the literature for AF determination in different matrices is provided as well in Table 2.
Human serum | ED of 0.5 mL sample with Pronase®, LLE degreasing with hexane and: LLE with acidified EtAc (for AFB1), QuEChERS (for FB1-lys) | [39] |
Human serum | ED of 0.25 mL sample with Pronase® and mixed-mode SPE. Elution with acidified MeOH | [48] |
Human plasma | PP of 0.23 mL sample with MeOH/water, supernatant ED with Pronase® and mixed-mode SPE. Elution with acidified MeOH | [26] |
Human plasma | PP of 0.1 mL sample with EtOH/ACN | [29] |
Human plasma | 3-step LLE of 0.1 mL sample with EtAc | [22] |
Human urine | IAC for 2 mL sample. Elution with MeOH | [40] |
Human breast milk | Simplified QuEChERS | [33] |
Pig plasma, urine, and feces. Broiler chicken plasma and excreta | Pig plasma: PP of 0.25 mL sample with ACN. Pig urine: LLE of 0.5 mL sample with EtAc. Pig feces: SLE of 0.25 g sample with acetone and SPE for phospholipid removal. Chicken plasma: PP of 0.15 mL sample with ACN and well-plates. Chicken excreta: SLE of 0.25 g sample with ACN | [49] |
Beer | QuEChERS for 5 mL sample | [24] |
Beer | On-line SPE for 0.5 mL sample. Elution with acidified ACN/CH3COONH4 | [25] |
Beer | SPE for 10 mL sample. Elution with ACN/MeOH | [23] |
Milk | PP of 4 g sample with ACN and MDSPE with 10 mg MNPs. Desorption with acidified EtAc | [42] |
Milk | QuEChERS for 10 mL sample | [41] |
Peach seed, milk powder, corn flour and beer | MAE of solid samples (0.2 g) in MeOH/water and DSPE with 2 mg zirconia NPs. Desorption with MeOH | [28] |
Maize | UAE of 0.7 g sample in acidified MeOH/dichloromethane/EtAc | [55] |
Maize | UAE of 0.5 g sample with acidified ACN | [30] |
Corn | UAE of 2 g sample in ACN/water and QuEChERS | [50] |
Cereal foods (flours and bread) | SLE of 10 g sample with ACN/water and SPE. Elution with MeOH | [44] |
Durum wheat pasta and baby food pasta | Simplified QuEChERS for 4 g sample | [45] |
Cashew nut | SLE of 1 g sample in MeOH/water and SPE. Elution with MeOH | [43] |
Coix seed | SLE of 5 g sample with acidified ACN | [37] |
Isoflavone supplements | SLE of 2.5 g sample with acidified ACN and clean-up by SPE | [34] |
Ginkgo biloba nutraceuticals | SLE of 2.5 g sample with acidified ACN and clean-up by DSPE | [35] |
Green tea and royal jelly supplements | SLE of 2.5 g sample with acidified ACN and clean-up by DSPE | [36] |
Green tea nutraceuticals | SLE of 1 g sample with acidified ACN and clean-up by DSPE | [31] |
Functional and medicinal herbs | SLE of 2 g sample with PBS, LLE degreasing with hexane and IAC. Elution with MeOH | [46] |
Pet foods | UAE of 2 g sample in acidified ACN and QuEChERS | [32] |
Feed | Simplified QuEChERS | [38] |
Surface and drinking waters | SPE for 100 mL sample. Elution with MeOH/water/acetone | [47] |
Snus | LLE with acidified EtAc | [27] |
Summary of the sample treatments used in the AF determination by LC-HRMS.
AFs are synthesized via multiple intermediates by a complex pathway in several species of the
As regards mycotoxin degradation, decontamination techniques for AFs in food and feed attract continuous interest due to their adverse health effects and large economic losses for producers. In this sense, physical, chemical and biological strategies have been proposed. Thus, ABF1 degradation products by electron beam irradiation have been identified, as well as the possible pathway, using UHPLC-Q-TOF-MS [61, 62]. High-voltage atmospheric cold plasma (HVACP) is other physical strategy applied for AFB1 decontamination, providing a 76% efficiency when the non-thermal treatment was applied for 5 min in air containing 40% relative humidity. Thus, molecular formulas of six degradation products were elucidated by HPLC-TOF and their structures were further studied by Orbitrap MS. Two of the detected degradation compounds were ozonolysis products of AFB1, and the other four indicated the action of other reactive species besides ozone, generated during HVACP treatment [63]. The proven degradation power of ultrasounds for AFB1 aqueous solutions allows to perceive this physical detoxification technology as promising for food industry. An ultrasound exposure of 80 min degraded AFB1 by 85.1%, being eight main reaction products identified by UHPLC-Q-Orbitrap [64]. The study of degradation pathways and structural identification of photodegradation products of AFB1 in aqueous medium [65], ACN [66] and on peanut surface [67], has been carried out using UHPLC-Q-TOF after ultraviolet irradiation of different intensities.
Biological degradation, mainly caused by bacterial and fungal enzymes, appears as a strategy for AFB1 removal, with inherent advantages over physical and chemical strategies such as being friendly to the environment. LC-Q-TOF has been applied in the monitorization of AFB1 degradation products, and the obtained results lead the authors to propose bacterial strain
AFs are secondary toxic metabolites which may be present mainly in contaminated food and biological samples at very low levels. Among them, AFB1 is considered the most toxic, being classified as a human carcinogen. The analysis of food and biological samples is very complex and includes different steps as extraction, clean-up, separation, and detection approaches. This chapter reports the main analytical procedures developed for the AF determination by LC-HRMS. Different sample preparation techniques have been proposed, being QuEChERS, SPE and SLE the more frequently used. New nanomaterials including magnetic nanoparticles have been recently applied as adsorbents, increasing extraction efficiency and specificity. Separation of AFs is usually performed using HPLC, which performance was improved when using UHPLC. Different detectors are proposed, being MS or MS/MS widely applied, ensuring a specific confirmation for targeted analysis. However, the toxicological pathway of AFs in biological samples leads to the appearance of modified or masked mycotoxins, whose structures must be accurately established, making their detection difficult using routine analytical methods. On the other hand, the lack of commercial analytical standards results a great challenge for accurate identification and quantitation of modified AFs. In this field, HRMS has proven to be a very effective tool to enable the rapid determination of both parent and modified AFs. The use of metabolomic platforms combined with HRMS is nowadays considered the most appropriate way to study the toxicokinetic behavior of AFs in order to establish, when possible, maximum tolerable intakes and to investigate whether they have any relationship with certain clinical pathologies and cancer processes.
The authors acknowledge the financial support of the Comunidad Autónoma de la Región de Murcia (CARM, Fundación Séneca, Project 19888/GERM/15), the Spanish MICINN (PGC2018-098363-B-100), the University of Murcia (R-987/2020) and the European Commission (FEDER).
AA | acetic acid |
ACN | acetonitrile |
AFAR | aflatoxin aldehyde reductase |
AFL | Aflatoxicol |
AFs | aflatoxins |
AFB1 | aflatoxin B1 |
AFB2 | aflatoxin B2 |
AFBO | aflatoxin-8,9-epoxide |
AFG1 | aflatoxin G1 |
AFG1 | aflatoxin G2 |
AFM1 | aflatoxin M1 |
AFM2 | aflatoxin M2 |
AFP1 | aflatoxin P1 |
AFQ1 | aflatoxin Q1 |
AIF | all-ion fragmentation |
AP | aputinic |
DART | direct analysis in real time |
2D | Two-dimensional |
dd-MS2 | data dependent |
DIA | data independent |
DMSPE | dispersive magnetic solid-phase extraction |
DPEP | dipeptidase |
DSPE | dispersive solid-phase extraction |
ED | enzymatic digestion |
ESI | electrospray ionization |
EtAc | ethyl acetate |
EtOH | ethanol |
FA | formic acid |
FAPy | formamidopyramidine |
FI | flow injection |
GGT | γ-glutamyltransferase |
GSH | glutathione |
GST | glutathione S-transferase |
HCD | high energy collision dissociation |
HESI | heated electrospray ionization |
HRMS | high resolution mass spectrometry |
HVACP | high-voltage atmospheric cold plasma |
IACs | immunoaffinity columns |
IARC | International Agency for Research on Cancer |
IDMS | isotope dilution mass spectrometry |
IT | ion trap |
LC | liquid chromatography |
LLE | liquid–liquid extraction |
LOD | limit of detection |
LOQ | limit of quantification |
lys | lysine |
MAE | microwave assisted extraction |
MDSPE | magnetic dispersed solid-phase extraction |
MeOH | methanol |
MS | mass spectrometry |
MS/MS | tandem mass spectrometry |
MWCNT | multi-walled carbon nanotubes |
NAT | N-acetyltransferase |
NPs | nanoparticles |
PBS | phosphate-buffered solution |
PFP | pentafluorophenyl |
PP | protein precipitation |
PRM | parallel reaction monitoring mode |
Q | quadrupole |
QqQ | triple quadrupole |
QuEChERS | quick easy cheap effective rugged and safe |
SIM | selected ion monitoring |
SLE | solid–liquid extraction |
SPE | solid-phase extraction |
TOF | time-of-flight |
TOF-SIMS | time-of-flight secondary ion mass spectrometry |
UAE | ultrasound assisted extraction |
UHPLC | ultra-high performance liquid chromatography |
WHO | World Health Organization. |
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