Selected Mass Frontier and mzCloud References




Biochemical Applications

Nagy, P.; Lechte, T. P.; Das, A. B.; Winterbourn, C. C. Conjugation of Glutathione to Oxidized Tyrosine Residues in Peptides and Proteins. Journal of Biological Chemistry 2012, 287, 26068. "Data were analyzed using Finnigan Xcalibur, Thermo Finnigan Qual Browser1.3, and HighChem Mass Frontier 3.0 programs. Identity of the peaks was established on the basis of characteristic MS/MS fragmentation patterns."
Banack, S. A.; Metcalf, J. S.; Jiang, L.; Craighead, D.; Ilag, L. L.; Cox, P. A. Cyanobacteria produce N-(2-aminoethyl) glycine, a backbone for peptide nucleic acids which may have been the first genetic molecules for life on earth. PloS one 2012, 7, e49043. “Predicted fragmentation pattern of AQC derivatized AEG (m/z 459) following collision-induced dissociation to produce daughter ions of m/z 171, 214, 289 and 119. Predicted structures were produced using High Chem Mass Frontier 5.1 software (High Chem Ltd., Slovak Republic).”
Vacek, J.; Kosina, P.; Gabrielová, E.; Modrianský, M.; Ulrichová, J. Ion-trap mass spectrometry for determination of 3,5,3′-triiodo-l-thyronine and 3,5,3′,5′-tetraiodo-l-thyronine in neonatal rat cardiomyocytes. Journal of Pharmaceutical and Biomedical Analysis 2010, 53, 688. “We also consulted the Mass Frontier 5.01.20 software database (HighChem, Ltd.; ca. 105 compounds are included) for possible interfering agents of molecular weights (±2 m/z) close to T3 or T4.”
Jiang, C.; Wu, B. Molecular cloning and functional characterization of a novel decarboxylase from uncultured microorganisms. Biochemical and Biophysical Research Communications 2007, 357, 421. "As shown in Fig. 4 , the enzymatic product showed a molecular ion at m/z 78.0, which is the same as the protonated cysteamine, suggesting cleavage of the –COOH group from L-cysteine. HighChem Mass Frontier software 3.0 was used to verify that the molecular ion observed correlated with the proposed structure."
Dunkle, M. N.; Herrmann, J. K.; Colón, H.; Pennington, C.; Colón, L. A. Evaluation of a fluorescein-labeled estradiol derivative for use in affinity capillary electrophoresis. Microchemical Journal 2006, 82, 100. “A software program, Mass Frontier 3.0 (High Chem) was used to verify the fragment ion structure for m/z 390.1 and m/z 505.9 as well as all other proposed fragment ion structures in Fig. 3.”

Free Radical Biology

Hawkins, C. L.; Morgan, P. E.; Davies, M. J. Quantification of protein modification by oxidants. Free Radical Biology and Medicine 2009, 46, 965. “Prediction of fragment mass structures can be achieved using fragmentation prediction software (e.g., Mass Frontier 4.0, HighChem Ltd, Slovak Republic)”


Benke, P.I., Kumar, M.V., Pan, D. and Swarup, S., 2015. A mass spectrometry-based unique fragment approach for the identification of microcystins. Analyst, 140(4), pp.1198-1206. “The unique fragments of the MC variants were identified by comparing the theoretical fragments predicted by Mass Frontier 7.0.5 SP3 spectral interpretation software”
Todd, D.A., Zich, D.B., Ettefagh, K.A., Kavanaugh, J.S., Horswill, A.R. and Cech, N.B., 2016. Hybrid Quadrupole-Orbitrap mass spectrometry for quantitative measurement of quorum sensing inhibition. Journal of microbiological methods, 127, pp.89-94. “Resulting spectra were compared to predicted fragmentation pattern of AIP ions. Fragmentation prediction was performed using Mass Frontier 7.0 (HighChem, Ltd., Slovak Republic).”

Photochemistry, Inorganic and Organometallic Chemistry


Inorganic Chemistry

Organometallic Chemistry

Szymura, J. A.; Lamkiewicz, J. Band composition analysis: a new procedure for deconvolution of the mass spectra of organometallic compounds. Journal of Mass Spectrometry 2003, 38, 817. "For more effective identification of unknowns with constantly growing NIST and other mass spectral (MS) libraries, a number of computer-aided MS classification methods had been elaborated, eg neural networks, self-organizing maps, cluster analysis and principal component analysis. All of them are included in Mass Frontier 3.0 software designed for mass spectral management, classification and interpretation."

Environmental Analysis

Degradation and Transformation Products

Rodayan, A.; Segura, P. A.; Yargeau, V. Ozonation of wastewater: Removal and transformation products of drugs of abuse. Science of The Total Environment 2014, 487, 763. "Normalized activation energy was set to 35, isolation width to 2 m/z and activation time to 30 ms. The file was subsequently deconvoluted with Mass Frontier 7.0 (HighChem Ltd., Bratislava, Slovakia)."
Joo, H.; Choi, K.; Hodgson, E. Human metabolism of atrazine. Pesticide Biochemistry and Physiology 2010, 98, 73. "Mass Frontier 4.0 software was used to predict the fragmentation pathways."
Sette, C. B.; Pedrete, T. d. A.; Felizzola, J.; Nudi, A. H.; Scofield, A. d. L.; Wagener, A. d. L. R. Formation and identification of PAHs metabolites in marine organisms. Marine Environmental Research. “In this work, a dissociation of mass precursor ion called MS2 or MS/MS was performed. In resume, the parent ions were detected and the product spectra acquired for identification using collision induced dissociation to produced MS2 spectra, identifying the origin of these molecules with Mass Frontier 5.0 software.”

Pollutants and Contaminants

Aceña, J., Heuett, N., Gardinali, P. and Pérez, S., 2016. Suspect Screening of Pharmaceuticals and Related Bioactive Compounds, Their Metabolites and Their Transformation Products in the Aquatic Environment, Biota and Humans Using LC-HR-MS Techniques. Comprehensive Analytical Chemistry, 71, pp.357-378. "…Pathway Prediction System (UM-PPS) and the Meteor Environmental Pathway Prediction System (Lhasa Limited, UK), or commercial software packages such as MetWorks or SIEVE for candidate detection, Xcalibur for data analysis, Mass Frontier (HighChem, Ltd, Bratislava, Slovakia)…"
Frank, R.A., Milestone, C.B., Rowland, S.J., Headley, J.V., Kavanagh, R.J., Lengger, S.K., Scarlett, A.G., West, C.E., Peru, K.M. and Hewitt, L.M., 2016. Assessing spatial and temporal variability of acid-extractable organics in oil sands process-affected waters. Chemosphere, 160, pp.303-313. "Principal component analysis (PCA; Mass Frontier 6.0 (Thermo Fisher Scientific and HighChem Ltd)), was utilized to investigate patterns and clustering of data with respect to spatial, temporal, and industrial variances."
Ferrando-Climent, L., Reid, M.J., Rodriguez-Mozaz, S., Barceló, D. and Thomas, K.V., 2016. Identification of markers of cancer in urban sewage through the use of a suspect screening approach. Journal of Pharmaceutical and Biomedical Analysis, 129, pp.571-580. "HE fragments identified in b) (above) were then checked against those predicted by Mass Frontier (HighChem software) which enables theoretical generation of mass fragments based on a proposed chemical structure."
Avagyan, R., Åberg, M. and Westerholm, R., 2016. Suspect screening of OH-PAHs and non-target screening of other organic compounds in wood smoke particles using HR-Orbitrap-MS. Chemosphere, 163, pp.313-321. "The elemental compositions were predicted and ChemSpider Database and mzCloud (HighChem LLC, Slovakia), a mass spectral database, were used for structural search."
Solliec, M., Roy-Lachapelle, A., Gasser, M.O., Coté, C., Généreux, M. and Sauvé, S., 2016. Fractionation and analysis of veterinary antibiotics and their related degradation products in agricultural soils and drainage waters following swine manure amendment. Science of The Total Environment, 543, pp.524-535. "After choosing the most intense product ions, fragmentation energy scans were carried out to obtain the optimal NCE for complete fragmentation of precursor ions. The exact masses of the product ions were obtained with Mass Frontier software (Highchem, Bratislava, Slovakia)"
Ferrando-Climent, L.; Rodriguez-Mozaz, S.; Barceló, D. Development of a UPLC-MS/MS method for the determination of ten anticancer drugs in hospital and urban wastewaters, and its application for the screening of human metabolites assisted by information-dependent acquisition tool (IDA) in sewage samples. Analytical and bioanalytical chemistry 2013, 1. "In order to confirm the presence/absence of unknown compounds in the samples, mass fragmentation mechanisms were evaluated with the help of Mass Frontier software, which simulates mass fragmentation pathways and mechanisms for compounds of interest"
Zedda, M.; Zwiener, C. Is nontarget screening of emerging contaminants by LC-HRMS successful? A plea for compound libraries and computer tools. Analytical and bioanalytical chemistry 2012, 403, 2493. "With the rule-based software program Mass Frontier [84], fragmentation spectra were generated for all candidates and then compared with the experimental collision-induced-dissociation spectra of Q-TOF-MS meas- urements of the unknown structures."
Triantis, T.; Tsimeli, K.; Kaloudis, T.; Thanassoulias, N.; Lytras, E.; Hiskia, A. Development of an integrated laboratory system for the monitoring of cyanotoxins in surface and drinking waters. Toxicon 2010, 55, 979. "Detection was performed in selected reaction monitoring mode (SRM) using the two most intense and characteristic precursor/product-ion transitions obtained from the MS–MS optimization procedure. Mass Frontier (v4.0, produced by HighChem Ltd.) software was used for the interpretation of fragmentation pathways and reaction mechanisms of the described compounds."
Krauss, M.; Singer, H.; Hollender, J. LC–high resolution MS in environmental analysis: from target screening to the identification of unknowns. Analytical and bioanalytical chemistry 2010, 397, 943. "The comparison of the predicted MS/MS spectrum of all database hits using the Mass Frontier software (HighChem, Bratislava, Slovakia) with the measured MS/MS spectrum ranked chloridazon-methyl-desphenyl first in the list of possible structures."
Barceló, D.; Petrovic, M. Challenges and achievements of LC-MS in environmental analysis: 25 years on. TrAC Trends in Analytical Chemistry 2007, 26, 2. "The comparison between the measured spectrum and the theoretical spectrum of metolachlor [M+H]+ (Fig. 7D) shows sufficient agreement of the isotopic pattern for the 37Cl signal and the mass error between theoretical and measured masses of 0.3 ppm for [M+H]. In order to confirm the identifications, the data-dependent MS2 spectra of the compound were compared to MS2 spectra predicted by Mass Frontier software."
ICE, I. C. E. Using a Triple Quadrupole Mass Spectrometer in Accurate Mass Mode and an Ion Correlation Program to Identify Compounds. Ion Composition Elucidation, EPA 2005. "The majority of these structures were predicted and drawn by the Mass Frontier 3.0 ion fragmentation program. A mass spectral interpretation expert provided the additional structures. For some ions, multiple structures were possible. But only one plausible structure is required to provide assurance that an ion could be formed from a protonated candidate molecule."

Food and Beverages

Food Chemistry

Gómez‐Pérez, M. L.; Romero‐González, R.; Plaza‐Bolaños, P.; Génin, E.; Martínez Vidal, J. L.; Garrido Frenich, A. Wide‐scope analysis of pesticide and veterinary drug residues in meat matrices by high resolution MS: detection and identification using Exactive‐Orbitrap. Journal of Mass Spectrometry 2014, 49, 27. "The procedure employed for the identification of the fragments involved three different approaches: (1) application of software tools available in the market; herein, HighChem Mass Frontier™ version 6.0 was chosen for our purpose. "
Oliveira, D. N.; Catharino, R. R. Direct metabolic fingerprinting of olive oils using STELDI-MS. Journal of Food Composition and Analysis 2014. "The proposed identification of the compounds was based on both MS/MS spectra and software calculations with Mass Frontier (v. 6.0, Thermo Fisher)."
Stojadinovic, M.; Radosavljevic, J.; Ognjenovic, J.; Vesic, J.; Prodic, I.; Stanic-Vucinic, D.; Cirkovic Velickovic, T. Binding affinity between dietary polyphenols and β-lactoglobulin negatively correlates with the protein susceptibility to digestion and total antioxidant activity of complexes formed. Food Chemistry 2013, 136, 1263. “Compounds were identified by combining exact masses, molecular formulae derived from Mass Frontier Spectral Interpretation Software and spectra from LTQ Orbitrap XL hybrid FTMS (Thermo Fisher Scientific, USA) with findings from the literature and internal database of spectra of standard polyphenol compounds.”
Fearnley, L.; Greenwood, D. R.; Schmitz, M.; Stephens, J. M.; Schlothauer, R. C.; Loomes, K. M. Compositional analysis of manuka honeys by high-resolution mass spectrometry: Identification of a manuka-enriched archetypal molecule. Food Chemistry 2012, 132, 948. “Identification of parent ions and their MSn –derived spectral trees was performed using the HighChem Mass Frontier ESI MS–MS spectral library and verified where possible by comparison with authentic standards and manual interpretation of MS/MS data coupled with atomic composition determination from accurate mass determination of parent ions.”
Stephens, J. M.; Schlothauer, R. C.; Morris, B. D.; Yang, D.; Fearnley, L.; Greenwood, D. R.; Loomes, K. M. Phenolic compounds and methylglyoxal in some New Zealand manuka and kanuka honeys. Food Chemistry 2010, 120, 78. “This data was consistent with 3,4,5-trimethoxybenzoic acid, as rationalized in silico using the Thermo HighChem MassFrontier 5 software package.”

Food Safety Control

Solliec, M., Roy‐Lachapelle, A. and Sauvé, S., 2015. Development of a suspect and non‐target screening approach to detect veterinary antibiotic residues in a complex biological matrix using liquid chromatography/high‐resolution mass spectrometry. Rapid Communications in Mass Spectrometry, 29(24), pp.2361-2373. "The statistical generation of production structures and the proposed mechanism of fragmentations to confirm the presence of any compounds were carried out with Mass Frontier software (Highchem, Bratislava, Slovakia)"
Pérez-Gálvez, A.; Ríos, J. J.; Roca, M. A new probe for tracking the presence of E141i food colorant. Food Control 2014. "Structure of product ions from the parent compound was predicted with the use of Mass Frontier TM 4.0. The program generates a fragmentation scheme for the drawn molecular structure using fragmentation rules of mass spectrometry known in the literature, as well as the selected ionization mode and the number of fragmentation steps"
Rubert, J.; James, K. J.; Mañes, J.; Soler, C. Applicability of hybrid linear ion trap-high resolution mass spectrometry and quadrupole-linear ion trap-mass spectrometry for mycotoxin analysis in baby food. Journal of Chromatography A 2012, 1223, 84. “In this context, all the samples were analysed on looking for emergent micotoxins, such as enniatins A, B, A1, B1 and fusaproliferin as it has been done in a previous work[23]. Mass Frontier 7.0 was used as complementary software in order to identify these compounds and unknowns in the 25 samples.”
Low, M.-Y.; Li, L.; Ge, X.; Kee, C.-L.; Koh, H.-L. Isolation and structural elucidation of flibanserin as an adulterant in a health supplement used for female sexual performance enhancement. Journal of Pharmaceutical and Biomedical Analysis 2012, 57, 104. "The fragmentation process is indicated in Fig. 5, which is confirmed by Mass Frontier™ 5.0 (HighChem, Ltd., Slovak Republic). All proposed fragments have mass errors below 5 ppm"
Khayoon, W. S.; Saad, B.; Lee, T. P.; Salleh, B. High performance liquid chromatographic determination of aflatoxins in chilli, peanut and rice using silica based monolithic column. Food Chemistry 2012, 133, 489. "The product ion m/z 241 was used for the quantification of AFB1whereas m/z 287, m/z 243 and m/z 313 were used as quantifier ions for AFB2, AFG1and AFG2, respectively. The proposed fragmentations pathways are shown in Fig 1. The accurate masses and molecular formulas of these four ions were obtained by using HighChem. Mass Frontier 6.0 software."
Channell, G. A.; Wulfert, F.; Taylor, A. J. Identification and Monitoring of Intermediates and Products in the Acrylamide Pathway Using Online Analysis. Journal of Agricultural and Food Chemistry 2008, 56, 6097. "MS Interpretation Mass Frontier software (HighChem Ltd., Bratislava, Slovakia) was used to predict fragmentation of compounds during ionization or under MS-MS conditions to provide supporting information for tentative identifications."
Reilly, C. A.; Yost, G. S. Metabolism of Capsaicinoids by P450 Enzymes: A Review of Recent Findings on Reaction Mechanisms, Bio-Activation, and Detoxification Processes*. Drug Metabolism Reviews 2006, 38, 685. " Identification and preliminary structural assignments were generated by interpretation of liquid-chromatographic-tandem mass spectrometric data and comparison to predicted mass spectra (Mass Frontier 4.0)."

MS Techniques

Compound Identification and Structure Elucidation

Kind, T.; Fiehn, O. Advances in structure elucidation of small molecules using mass spectrometry. Bioanalytical reviews 2010, 2, 23. "Currently, only Mass Frontier (HighChem Ltd.) contains a large fragmentation library of 30,936 fragmentation schemes with 129,229 reactions and 151,762 associated structures. ...The representation of a spectral tree (see Fig. 11) of compound mass spectra and their associated structures was obtained from MassFrontier (HighChem Ltd)."
Sheldon, M. T.; Mistrik, R.; Croley, T. R. Determination of Ion Structures in Structurally Related Compounds Using Precursor Ion Fingerprinting. Journal of the American Society for Mass Spectrometry 2009, 20, 370. "Database and search capabilities were performed with commercially available Mass Frontier™ 5.0 software. Microsoft SQL database is implemented in Mass Frontier. This software also contains search algorithm specially developed for comparison of MS/MS spectra. Average PC computer power is necessary. The complete PIF system will be implemented into this software."
Klagkou, K.; Pullen, F.; Harrison, M.; Organ, A.; Firth, A.; Langley, G. J. Approaches towards the automated interpretation and prediction of electrospray tandem mass spectra of non-peptidic combinatorial compounds. Rapid Communications in Mass Spectrometry 2003, 17, 1163. "Mass Frontier employs principal component analysis (PCA) as a classification method. The aim of PCA is to find a new coordinate system that can be expressed as the linear combination of the original variables, ie m/z ratios, so that the major trends in the data are described.”

All Ion Frgamentation

Oppermann, M.; Damoc, N.; Crone, C.; Moehring, T.; Muenster, H.; Hornshaw, M. In Plant Metabolomics; Hardy, N. W., Hall, R. D., Eds.; Humana Press: 2012; Vol. 860, p 145. "Here, we have used a two-pronged approach based on accurate mass determination for confirmatory elemental composition matching with a secondary strategy of matching MS/MS product ion data against theoretical fragmentation patterns derived with Mass Frontier™ software."
Kusebauch, B.; Brendel, N.; Kirchner, H.; Dahse, H.-M.; Hertweck, C. Assessing Oxazole Bioisosteres as Mutasynthons on the Rhizoxin Assembly Line. ChemBioChem 2011, 12, 2284. "Accurate masses from AIF MS/MS scans allowed us to assign experimentally obtained product ions to fragments predicted by the Mass Frontier software"

Electron Ionization

Lai, Z. and Fiehn, O., 2016. Mass spectral fragmentation of trimethylsilylated small molecules. Mass Spectrometry Reviews. 2016, 9999, pp.1–13. "MassFrontier software (Mistrik, 1998) has mostly been used in LC-MS/MS annotations, it can indeed also exclude false isomers in trimethylsilylated metabolites (Kumari et al., 2011) by interpretation of fragmentation pathways based on its HighChem fragmentation library"
Plassmeier, J.; Persicke, M.; Pühler, A.; Sterthoff, C.; Rückert, C.; Kalinowski, J. Molecular characterization of PrpR, the transcriptional activator of propionate catabolism in Corynebacterium glutamicum. Journal of Biotechnology 2012, 159, 1. "Virtual fragmentations were performed with the Mass Frontier 2.0. The GC–MS used here had a linear detection range ofat least three orders of magnitude and a standard error of 7.6%"
Damascelli, A.; Palmisano, F. Sesquiterpene Fingerprinting by Headspace SPME–GC–MS: Preliminary Study for a Simple and Powerful Analytical Tool for Traceability of Olive Oils. Food Anal. Methods 2012, 1. "This assignment was further corroborated by interpretation of the observed fragmentation pattern aided by HighChem Mass Frontier ver. 1.0 software package."
Lu, Y.; Hong, S.; Tjonahen, E.; Serhan, C. N. Mediator-lipidomics: databases and search algorithms for PUFA-derived mediators. Journal of Lipid Research 2005, 46, 790. "For LMs and related compounds for which synthetic and authentic standards were available, the databases were constructed with MassFrontier (version 2.0; HighChem, Ltd.) (22), a commercial software designed for use with positive-ion MS spectra generated by electron mpact ionization. ... Identification of 11,15S-dihydroxy-9-oxo-prosta-5Z,13E-dien-1-oic acid (PGE2) generated by rabbit leukocytes using a mediator-lipidomic database and algorithm developed with MassFrontier."

Fourier Transformation / Orbitrap

Liu, T.; Du, F.; Zhu, F.; Xing, J. Metabolite identification of artemether by data-dependent accurate mass spectrometric analysis using an LTQ-Orbitrap hybrid mass spectrometer in combination with the online hydrogen/deuterium exchange technique. Rapid Communications in Mass Spectrometry 2011, 25, 3303. "The fragmentation predicted by Mass Frontier 6.0 (Thermo Fisher Scientific) was based on general fragmentation rules of the even-electron protonated molecule, allowing for bond cleavage with hydrogen rearrangement and subsequent isomerization and stabilization."

Isotope Labeling and Radiation

Mu, L.; Hesselmann, R.; Oezdemir, U.; Bertschi, L.; Blanc, A.; Dragic, M.; Schibli, R. Identification, characterization and suppression of side-products formed during the synthesis of high dose 68Ga-DOTA-TATE. Applied Radiation and Isotopes 2013, 76, 63. "Advanced structure elucidation to compare generated fragments with the product structure was calculated respectively and postulated using accurate mass measurements in combination with structural information using the Mass Frontier 6.0 software (HighChem Ltd., Slovak Republic)"
Koubaa, M.; Mghaieth, S.; Thomasset, B.; Roscher, A. Gas chromatography–mass spectrometry analysis of 13C labeling in sugars for metabolic flux analysis. Analytical Biochemistry 2012, 425, 183. “Fragmentation was simulated by Mass Frontier 5.0 and, where necessary, confirmed by the use of specifically 13C-labeled standards ([glc-13C6]sucrose; [fru-13C6]sucrose; [1-13C]-, [1,2-13C2]-,[2-13C]-, [6-13C]-, and [U-13C]glucose; and [2-13C]-, [6-13C]-, and[U-13C]fructose, all from Euriso-Top except 6-13C-labeled sugars from Isotec, Miamisburg, OH, USA.”
Wissenbach, D.; Meyer, M.; Remane, D.; Philipp, A.; Weber, A.; Maurer, H. Drugs of abuse screening in urine as part of a metabolite-based LC-MSn screening concept. Analytical and bioanalytical chemistry 2011, 400, 3481. “Software TF Xcalibur 2.1.0 was used for data acquisition, NIST MS Search 2.0 (National Institute of Standards and Technology, Gaithersburg, MD, USA) for library generation, Mass Frontier (Highchem, Bratislava, Slovakia) for prediction of MS2 and MS3 fragments, and TF ToxID 2.1.1 for target screening in the MS2 screening mode”


Wissenbach, D. K.; Meyer, M. R.; Remane, D.; Weber, A. A.; Maurer, H. H. Development of the first metabolite-based LC-MSn urine drug screening procedure-exemplified for antidepressants. Analytical and bioanalytical chemistry 2011, 400, 79. "TF Xcalibur 2.1.0 was used for data acquisition, NIST MS Search 2.0 (National Institute of Standards and Technology, Gaithersburg, MD) for library generation, MassFrontier (Highchem, Bratislava, Slovakia) for prediction of MS2 and MS3 fragments"
Hollender, J.; Singer, H.; Hernando, D.; Kosjek, T.; Heath, E. The challenge of the identification and quantification of transformation products in the aquatic environment using high resolution mass spectrometry. Xenobiotics in the Urban Water Cycle 2010, 195. "By comparing the measured HR-MSMS with predicted mass spectra proposed by the software Mass Frontier along with estimated retention times for all possible structures from the data base search, the best match for the identified elemental composition was determined to be chloridazon-methyl-desphenyl."
Stoev, G.; Nazarov, V. Identification of the related substances of tilmicosin by liquid chromatography/ion trap mass spectrometry. Rapid Communications in Mass Spectrometry 2008, 22, 1993. "The LC system included a degasser, pump, and an autosampler. The system operated with Xcalibur software (version 1.1) and Mass Frontier 4.0"



Bhandari, D. R.; Schott, M.; Römpp, A.; Vilcinskas, A.; Spengler, B. Metabolite localization by atmospheric pressure high-resolution scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging in whole-body sections and individual organs of the rove beetle Paederus riparius. Analytical and bioanalytical chemistry 2014, 1. “The software Mass Frontier™™ version 7.0 was used to generate possible fragment ions from pederin and pseudopederin. The theoretical fragments generated by the software were identical to the observed fragments in our experiment.“
Ferreira, M. S.; Oliveira, D. N.; Oliveira, R. N.; Allegretti, S. M.; Vercesi, A. E.; Catharino, R. R. Mass spectrometry imaging: a new vision in differentiating Schistosoma mansoni strains. Journal of Mass Spectrometry 2014, 49, 86. “Their structures were later inputted in MASS FRONTIER software v.6.0 (Thermo Scientific, CA, USA), here a number of fragments and mechanisms were modeled. MASS FRONTIER uses literature data and mathematical calculations to propose fragmentation mechanisms and products. [21] Structures were assigned to molecules that presented the highest number of matches between MS/MS experimental data and MASS FRONTIER fragments“




Zhang, J.; Huang, Z.; Chen, M.; Xia, Y.; Martin, F. L.; Hang, W.; Shen, H. Urinary metabolome identifies signatures of oligozoospermic infertile men. Fertility and sterility 2014. "For each potential biomarker, several candidates were provided by databases. Candidates at the top of the list were subjected to further MS/MS experiments, where target molecules were validated by characteristics of their product ions with Mass Frontier software"
Fonteh, Alfred N.; Michael G. Harrington. "Methods of determining levels of free amino acids and dipeptides and diagnosing Alzheimer's disease." U.S. Patent 8,670,941, issued March 11, 2014. "Tandem MS is used to obtain the major product ions, which are verified using a product ion scan followed by fragmentation by increasing collisional induced dissociation (CID) pressure. Mechanism of formation of specific products is verified using Mass Frontier software"
Zou, W.; She, J.; Tolstikov, V. V. A comprehensive workflow of mass spectrometry-based untargeted metabolomics in cancer metabolic biomarker discovery using human plasma and urine. Metabolites 2013, 3, 787. "The theoretical fragments generated by Mass Frontier are compared to those acquired from FT-ICR MS. Parent compounds with the best match of MSn fragmentation pattern are considered as the molecular structures of the potential biomarkers. The latest version of Mass Frontier™ enables one to build up a library of accurate mass ion tree spectra so that unknown identification is even more reliable."

Environmental Metabolomics


Vafiadi, C.; Topakas, E.; Bakx, E. J.; Schols, H. A.; Christakopoulos, P. Structural characterisation by ESI-MS of feruloylated arabino-oligosaccharides synthesised by chemoenzymatic esterification. Molecules 2007, 12, 1367. "The fragment at m/z 433 shown in Figure 1A is formed after the ring cleavage predicted using the theoretical fragmentation software Mass Frontier 5.0, establishing the linkage of ferulic acid to the O-5 position of the non-reducing end of the oligosaccharide."


Tan, A. H. M.; Chong, W. P. K.; Ng, S. W.; Basri, N.; Xu, S.; Lam, K. P. Aberrant Presentation of Self-Lipids by Autoimmune B Cells Depletes Peripheral iNKT Cells. Cell reports 2014, 9, 24. "Peaks with matches within a 10 ppm mass accuracy window were assigned putative identities, some of which were verified by matching observed MS2 fragmentation patterns with theoretical fragments generated by Mass Frontier 5.1 software (HighChem) as standards were not commercially available."
Zhong, W.; Zhao, Y.; Tang, Y.; Wei, X.; Shi, X.; Sun, W.; Sun, X.; Yin, X.; Sun, X.; Kim, S.; McClain, C. J.; Zhang, X.; Zhou, Z. Chronic Alcohol Exposure Stimulates Adipose Tissue Lipolysis in Mice: Role of Reverse Triglyceride Transport in the Pathogenesis of Alcoholic Steatosis. The American Journal of Pathology 2012, 180, 998. “For the confirmative metabolite identification, Mass Frontier 6.0 was used to generate the in silico MS/MS spectrum for each of the tentatively assigned metabolite candidates, and the in silico MS/MS spectrum was then matched to the experimental MS/MS spectrum of the metabolite ion. The metabolite candidate with the best MS/MS spectrum match was considered as the metabolite present in the sample."
Balvers, M. G. J.; Verhoeckx, K. C. M.; Plastina, P.; Wortelboer, H. M.; Meijerink, J.; Witkamp, R. F. Docosahexaenoic acid and eicosapentaenoic acid are converted by 3T3-L1 adipocytes to N-acyl ethanolamines with anti-inflammatory properties. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2010, 1801, 1107. "Mass Frontier 5.0 software (HighChem, Slovak Republic) was used to predict the fragmentation pattern for the NAE structure from EPA. ...As shown in Fig. 2, the high-resolution MS/MS dissociation analysis of EPEA (m/z 346.27) yielded fragments at m/z 328.26 (−18; loss of H2O) and 285.22 (−61; loss of ethanolamine), which were also predicted by Mass Frontier."
Megli, F. M.; Russo, L. Different oxidized phospholipid molecules unequally affect bilayer packing. Biochimica et Biophysica Acta (BBA) - Biomembranes 2008, 1778, 143. “Based on other authors' tandem MS analysis of the products of the Fenton reaction, oxidized molecular species were recognized by use of the Mass Frontier software yielding the calculated molecular weight of selected structures and related isotopic distribution.”
Serhan, C. N.; Hong, S.; Lu, Y. Lipid mediator informatics-lipidomics: novel pathways in mapping resolution. The AAPS journal 2006, 8, 284. "For comparison, Mass Frontier was also used to identify peak III, which also identified it as 15-HETE."
Lu, Y.; Hong, S.; Tjonahen, E.; Serhan, C. N. Mediator-lipidomics: databases and search algorithms for PUFA-derived mediators. Journal of Lipid Research 2005, 46, 790. "For LMs and related compounds for which synthetic and authentic standards were available, the databases were constructed with MassFrontier (version 2.0; HighChem, Ltd.) (22), a commercial software designed for use with positive-ion MS spectra generated by electron mpact ionization. ... Identification of 11,15S-dihydroxy-9-oxo-prosta-5Z,13E-dien-1-oic acid (PGE2) generated by rabbit leukocytes using a mediator-lipidomic database and algorithm developed with MassFrontier."

Metabolic Flux Analysis

Koubaa, M.; Thomasset, B.; Roscher, A. Quantifying 13C-labeling in Free Sugars and Starch by GC-MS. In Plant Metabolic Flux Analysis 2014, 121. "MS control and spectral processing are carried out using Xcalibur software, version 2.0.7. 5. Fragmentation simulation software: Mass Frontier 5.0 (HighChem Ltd.)"
Koubaa, M.; Mghaieth, S.; Thomasset, B.; Roscher, A. Gas chromatography–mass spectrometry analysis of 13C labeling in sugars for metabolic flux analysis. Analytical Biochemistry 2012, 425, 183. “Fragmentation was simulated by Mass Frontier 5.0 and, where necessary, confirmed by the use of specifically 13C-labeled standards ([glc-13C6]sucrose; [fru-13C6]sucrose; [1-13C]-, [1,2-13C2]-,[2-13C]-, [6-13C]-, and [U-13C]glucose; and [2-13C]-, [6-13C]-, and[U-13C]fructose, all from Euriso-Top except 6-13C-labeled sugars from Isotec, Miamisburg, OH, USA.”

Metabolic Profiling

Kim, H.Y., Park, H.M., Singh, D. and Lee, C.H., 2016. Metabolomic and Transcriptomic Comparison of Solid-State and Submerged Fermentation of Penicillium expansum KACC 40815. PloS one, 11(2), p.e0149012. “The MSn fragmentation pattern of each metabolite was compared with the simulated character of fragmentation using Mass frontier software 4.0 (Highchem, Bratislava, Slovakia).”
Wang, X., Wei, H., Cao, J., Li, Z. and He, P., 2015. Metabolomics analysis of muscle from piglets fed low protein diets supplemented with branched chain amino acids using HPLC‐high‐resolution MS. Electrophoresis, 36(18), pp.2250-2258. “Interpretation of MS/MS product ion spectra and prediction of fragment ions based chemical structures of the metabolites were performed by Mass Frontier software.”
Lee, H., Kim, E., Shin, Y., Lee, J.H., Hur, H.G. and Kim, J.H., 2016. Identification and formation pattern of metabolites of cyazofamid by soil fungus Cunninghamella elegans. Applied Biological Chemistry, 59(1), pp.9-14. “The proposed structures for the fragment ions of the ion m/z 341 were determined using Mass Frontier™ software (version 6.0, HighChem, Ltd., Slovakia).”
Ramakrishnan, P., Nair, S. and Rangiah, K., 2016. A method for comparative metabolomics in urine using high resolution mass spectrometry. Journal of Chromatography A, 1443, pp.83-92. “Final confirmation of a few tobacco metabolites was done using the advanced mass spectral database, mzCloud. For this, the respective mzML files were used as input for the mzCloud search.”
Xiao, J. F.; Zhou, B.; Ressom, H. W. Metabolite identification and quantitation in LC-MS/MS-based metabolomics. TrAC Trends in Analytical Chemistry 2012, 32, 1. “Currently, there are about 5000 manually-collected fragmentation rules involving around 19,000 reactions in the Mass Frontier Fragmentation Library. These fragmentation rules are used to predict possible product ions in MS/MS experiments. The advantage of a rule- based approach is its potentially high specificity. Not only are the general fragmentation rules used in in-silico fragmentation, but also those specific for a particular class of compounds.”
Zang, L.; Frenkel, R.; Simeone, J.; Lanan, M.; Byers, M.; Lyubarskaya, Y. Metabolomics Profiling of Cell Culture Media Leading to the Identification of Riboflavin Photosensitized Degradation of Tryptophan Causing Slow Growth in Cell Culture. Analytical Chemistry 2011, 83, 5422. "Its MS/MS fragmentation generated using LTQ-Orbitrap MS showed several major fragment ions with m/z of 220.06, 202.05, 192.07, and 174.05 amu (data not shown), which is consistent with the fragmentation pattern of NFK predicted by MassFrontier. ...The molecular formulas of the unknowns were first predicted from the accurate m/z of the ions. The assigned structures were verified by theoretical fragmentations generated by Mass Frontier v5.1"
Losito, I.; Conte, E.; Introna, B.; Megli, F. M.; Palmisano, F. Improved specificity of cardiolipin peroxidation by soybean lipoxygenase: a liquid chromatography - electrospray ionization mass spectrometry investigation. Journal of Mass Spectrometry 2011, 46, 1255. „The interpretation of MS/MS spectra was performed with the aid of the Mass Frontier (HighChem Ltd., Bratislava, Slovakia) software and by comparison with the existing literature on ESI-MS, MS/MS analysis of oxidized cardiolipins.“
Kumari, S.; Stevens, D.; Kind, T.; Denkert, C.; Fiehn, O. Applying In-Silico Retention Index and Mass Spectra Matching for Identification of Unknown Metabolites in Accurate Mass GC-TOF Mass Spectrometry. Analytical Chemistry 2011, 83, 5895. “Mass Frontier Software Mass Frontier 6.0 software [HighChem, Ltd., Slovakia, (vs, 2009] has been used to predict the fragmentation pathways. Generation of fragments for all candidate structures using Mass Frontier was implemented using the Batch Processing function, along with the SDF file, containing all candidate structures as input”
Hill, D. W.; Kertesz, T. M.; Fontaine, D.; Friedman, R.; Grant, D. F. Mass Spectral Metabonomics beyond Elemental Formula: Chemical Database Querying by Matching Experimental with Computational Fragmentation Spectra. Analytical Chemistry 2008, 80, 5574. "One of these programs (Mass Frontier) can also be run in a mode that predicts fragmentation ions by retrieving examples of structure type fragmentation mechanisms from a library of specific fragmentation mechanisms published in the mass spectral literature."

Metabolome Analysis

Kasper, P. T.; Rojas-Chertó, M.; Mistrik, R.; Reijmers, T.; Hankemeier, T.; Vreeken, R. J. Fragmentation trees for the structural characterisation of metabolites. Rapid Communications in Mass Spectrometry 2012, 26, 2275. "The only software available at the moment which can be used to analyse and/or compare MSn spectra is Mass Frontier (HighChem, Bratislava, Slovakia)."
Tolstikov, V.; Fiehn, O.; Tanaka, N. In Metabolomics; Weckwerth, W., Ed.; Humana Press: 2007; Vol. 358, p 141. „Structure elucidation and assignment, with the use of an ion trap mass spectrometer providing the fragmentation pathway, gets uncomplicated when the source of substance is known and fragments generated are in agreement with the predicted ones (Mass Frontier, HighChem), as illustrated in Fig. 5.“

Metabolomics and Diseases

Tartik, M., Darendelioglu, E., Aykutoglu, G. and Baydas, G., 2016. Turkish propolis supresses MCF-7 cell death induced by homocysteine. Biomedicine & Pharmacotherapy, 82, pp.704-712. "The “” was preferred as references database to analyse the accurate mass of the constituents of sample."
Wei, X.; Shi, X.; Zhong, W.; Zhao, Y.; Tang, Y.; Sun, W.; Yin, X.; Bogdanov, B.; Kim, S.; McClain, C. Chronic Alcohol Exposure Disturbs Lipid Homeostasis at the Adipose Tissue-Liver Axis in Mice: Analysis of Triacylglycerols Using High-Resolution Mass Spectrometry in Combination with In Vivo Metabolite Deuterium Labeling. PloS one 2013, 8, e55382. "To narrow down the metabolite candidates generated by database searching, the MS/MS spectra of metabolite peaks with significant concentration changes between two sample cohorts were acquired on LTQ-MS/MS. Each experimental MS/MS spectrum was compared to the in silico MS/MS spectra of all metabolite candidates using Mass Frontier 6.0"
Zhou, L.; Wang, Q.; Yin, P.; Xing, W.; Wu, Z.; Chen, S.; Lu, X.; Zhang, Y.; Lin, X.; Xu, G. Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases. Analytical and bioanalytical chemistry 2012, 1. "Also, the fragments of possible endogenous compounds searched from Chemspider ( and KEGG ( were analyzed with the MassFrontier 6.0 software (HighChem, Slovakia)."

Natural Products and Dereplication

Shevlyakova, O.A., Vasil’ev, K.Y., Ikhalainen, A.A., Antokhin, A.M., Taranchenko, V.F., Goncharov, V.M., Mitrofanov, D.A., Aksenov, A.V., Rodin, I.A. and Shpigun, O.A., 2016. Identification of Barrenwort flavonoids by high-resolution tandem mass spectrometry. Journal of Analytical Chemistry, 71(8), pp.768-776. "Based on the assumed structures of characteristic fragment ions obtained earlier by means of HighChem Mass Frontier and HyperChem software [27], the proposed mechanism of the fragmentation of Barrenwort flavonoids can be schematically presented in Fig. ..."
Cajka, T., Garay, L.A., Sitepu, I.R., Boundy-Mills, K.L. and Fiehn, O., 2016. Multiplatform Mass Spectrometry-Based Approach Identifies Extracellular Glycolipids of the Yeast Rhodotorula babjevae UCDFST 04-877. Journal of Natural Products, 79(10), pp.2580-2589. "In order to confirm the complete, intact structures of the observed glycolipids, Mass Frontier software was used to evaluate and interpret mass spectral data based on acquired MS/MS spectra and proposed structures."
Winzer, T., Graham, I.A. and Walker, T.C., Sun Pharmaceutical Industries (Australia) Pty Ltd, 2016. Biosynthesis of opiate alkaloids. U.S. Patent Application 15/182,761. "Fragments were reconciled against theoretical fragments generated by submitting candidate parent structures to Mass Frontier software (version 5.01.2; HighChem, Bratislava, Slovakia)."
Wang, C. H.; Wu, C. S.; Qin, H. L.; Zhang, J. L. Rapid discovery and identification of 68 compounds in the active fraction from Xiao–Xu–Ming decoction (XXMD) by HPLC–HRMS and MTSF technique. Chinese Chemical Letters 2014. “HRMS and multiple-stage mass spectrometric data of all detected compounds were obtained and changed to mass spectral tree data by Mass Frontier version 7.0 software“
Doroghazi, James R., Jessica C. Albright, Anthony W. Goering, Kou-San Ju, Robert R. Haines, Konstantin A. Tchalukov, David P. Labeda, Neil L. Kelleher, and William W. Metcalf. A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nature Chemical Biology 2014, 10, 963. "Structures for putatively identified compounds were fragmented in silico using the software suite Mass Frontier (Thermo Fisher Scientific, Waltham, MA). Both general fragmentation rules and fragmentation library modes were used. The fragmentation library was composed of the HighChem ESI Positive 2008 library, as well as annotated spectra from in-house compound libraries."
Xu, W.; Zhang, J.; Huang, Z.; Qiu, X. Identification of new dianthrone glycosides from Polygonum multiflorum Thunb. using high-performance liquid chromatography coupled with LTQ-Orbitrap mass spectrometry detection: a strategy for the rapid detection of new low abundant metabolites from traditional Chinese medicines. Analytical Methods 2012, 4, 1806. "Data analysis software (Mass Frontier 5.1) was employed to confirm manual elucidation of mechanisms and fragment ion structures. Mass Frontier predicts and displays comprehensive fragmentation pathways based on a set of general ionization, fragmentation, and rearrangement rules and by automatically extracting a decomposition mechanism for each fragmentation reaction in the fragmentation library."
Surowiec, I.; Nowik, W.; Moritz, T. Mass spectrometric identification of new minor indigoids in shellfish purple dye from Hexaplex trunculus. Dyes and Pigments 2012, 94, 363. "Addition ally, the presence of ions at m/z 132 for the known indigoids and m/z 131 for compound A suggests they have analogous structures with CO/CNH group differences, as indicated by analysis of the fragmentation pathway in Mass Frontier (Fig. 4)."
Abas, F.; Shaari, K.; Israf, D. A.; Syafri, S.; Zainal, Z.; Lajis, N. H. LC–DAD–ESI-MS analysis of nitric oxide inhibitory fractions of tenggek burung (Melicope ptelefolia Champ. ex Benth.). Journal of Food Composition and Analysis 2010, 23, 107. The mass spectra were acquired using ThermoFinnigan model LCQ DECA (San Jose, CA, USA) ion-trap mass spectrometer equipped with an ESI source interface and controlled by Xcalibur 1.2 and Mass Frontier 3.0 software.
Kim, D.; Lee, J. S.; Park, Y. K.; Kim, J. F.; Jeong, H.; Oh, T. K.; Kim, B. S.; Lee, C. H. Biosynthesis of antibiotic prodiginines in the marine bacterium Hahella chejuensis KCTC 2396. Journal of Applied Microbiology 2007, 102, 937. "This indicated the presence of novel prodigiosin analogues, the structural identification of which was carried out by an MS/MS fragmentation study using Mass Frontier software v4.0 (HighChem Ltd., Bratislava)."


Urayama, S.; Zou, W.; Brooks, K.; Tolstikov, V. Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer. Rapid Communications in Mass Spectrometry 2010, 24, 613. "The chemical structures that corresponded to the elemental formula were saved and imported to Mass Frontier 5.0 (HighChem Ltd, Bratislava, Slovakia) for the MS–MS fragmentation modeling analysis."

Plant Metabolomics

Van Meulebroek, L.; Bussche, J. V.; De Clercq, N.; Steppe, K.; Vanhaecke, L. A metabolomics approach to unravel the regulating role of phytohormones towards carotenoid metabolism in tomato fruit. Metabolomics 2014, 1. "To this extent, all candidate compound structures were processed by Mass Frontier 5.0 (Thermo Fisher Scientific, San José, USA), predicting fragmentation spectra of protonated and deprotonated molecules, using the general and library fragmentation mechanisms."
Jia, Z.; Wu, C.; Jin, H.; Zhang, J. Identification of the chemical components of Saussurea involucrata by high‐resolution mass spectrometry and the mass spectral trees similarity filter technique. Rapid Communications in Mass Spectrometry 2014, 28, 2237. "Mass Frontier™ 6.0 software (Thermo Fisher Scientific, San Jose, CA, USA) was used to collect mass spectral trees data comprising full-scan mass spectra from the target template compounds as the stem and multiple-stage mass spectra from the target template compounds as the branches in order to form the library."
Kim, H. Y.; Park, H. M.; Lee, C. H. Mass spectrometry‐based chemotaxonomic classification of Penicillium species (P. echinulatum, P. expansum, P. solitum, and P. oxalicum) and its correlation with antioxidant activity. Journal of Microbiological Methods 2012, 90, 327. “The MSn fragmentation pattern of each metabolite was compared with simulated character of fragmentation by using the Mass Frontier software 4.0 (HighChem, Bratislava, Slovakia).”
Sengkhamparn, N.; Bakx, E. J.; Verhoef, R.; Schols, H. A.; Sajjaanantakul, T.; Voragen, A. G. J. Okra pectin contains an unusual substitution of its rhamnosyl residues with acetyl and alpha-linked galactosyl groups. Carbohydrate Research 2009, 344, 1842. “The comparison of Mass Frontier 5.0 was used for identifying unknown fragments. MS2 experimental fragments with those of the prediction fragment software Mass Frontier 5.1 led to identification of hit compounds.”

Pharmaceutical Applications

Characterization of impurities and degradation products

Tiwari, R. N.; Bonde, C. G. Identification and characterization of degradation products of lacosamide by liquid-chromatography/time-of-flight mass spectrometric and multi-stage mass spectrometric analysis. Journal of Liquid Chromatography & Related Technologies 2014, 37, 2046. "Taking the help of Mass Frontier Software and Elemental Composition Calculator, a best possible molecular formula was generated for DP-I, showing that acetamide moiety of the drug underwent hydrolysis and led the loss of acetyl group that resulted in the formation of DP-I."
Chopra, S.; Van Schepdael, A.; Hoogmartens, J.; Adams, E. Characterization of impurities in tylosin using dual liquid chromatography combined with ion trap mass spectrometry. Talanta 2013, 106, 29.Mass Frontier software version 2.0 was used to simulate and study the fragmentation behavior of the described compounds. The “Fragments & Mechanisms” module in this software was used for a better understanding of the fragmentation behavior of the described components”
Chopra, S.; Pendela, M.; Hoogmartens, J.; Van Schepdael, A.; Adams, E. Impurity profiling of capreomycin using dual liquid chromatography coupled to mass spectrometry. Talanta 2012, 100, 113. “Besides the data obtained from the LC/MS experiments, the ‘‘Fragments & Mechanisms’’ module in the Mass Frontier software version 2.0 was also used for a better understanding of the fragmentation behavior of CMN.”
Tiwari, R. N.; Bonde, C. G. LC, LC–MS/TOF and MSn studies for the identification and characterization of degradation products of nelfinavir mesylate. Journal of Pharmaceutical and Biomedical Analysis 2011, 55, 435. “Taking the help of Mass Frontier Software and Elemental Composition Calculator, a best possible molecular formula was generated for DP-I, showing that N-tert-butyldecahydroisoquinoline-3-carboxamide moiety of the drug underwent hydrolysis involving cleavage of loosely heldcarbon-nitrogen bond.”
Li, B.; Van Schepdael, A.; Hoogmartens, J.; Adams, E. Characterization of impurities in tobramycin by liquid chromatography–mass spectrometry. Journal of Chromatography A 2009, 1216, 3941.Mass Frontier software version 2.0 was used to simulate and study the fragmentation behaviour of the described compounds.”

Drug Metabolism / Metabolite ID

Jeong, H.U., Kim, J.H., Kong, T.Y., Choi, W.G. and Lee, H.S., 2016. Comparative metabolism of honokiol in mouse, rat, dog, monkey, and human hepatocytes. Archives of pharmacal research, 39(4), pp.516-530. "Higher-energy collision dissociation with nitrogen gas and collision energy of 20–55 eV were used to obtain product ion spectra. Proposed structures for product ions were determined using Mass Frontier software version 6.0 (HighChem, Ltd., Bratislava, Slovakia)"
Lu, D., Zhang, S., Wang, D., Feng, C., Liu, S., Xu, Q., Lin, Y., Wu, C., Tang, L., She, J. and Wang, G., 2016. Identification of flurochloridone metabolites in rat urine using liquid chromatography/high resolution mass spectrometry. Journal of Chromatography A, 1445, pp.80-92. "Library identification was established via Mass Frontier with satisfactory performance. The MS1 and MS2 spectra of all the potential positive peaks were separately exacted using MetWorks™ 1.3 SP4 (Thermo Fisher Scientific) and straightly exported into Mass Frontier™ 7.0 (HighChem, LLC) to establish a metabolite library."
Roessner, U. and Hall, R.D., 2014. Metabolomics continues to flourish: highlights from the 2014 Metabolomics Society Conference. Metabolomics, 10(5), p.772. "Robert Mistrik, talked about progress with mzCloud (, towards a computational and database framework for compound identification."
Vaniya, A. and Fiehn, O., 2015. Using fragmentation trees and mass spectral trees for identifying unknown compounds in metabolomics. TrAC Trends in Analytical Chemistry, 69, pp.52-61. "However, most mass spectral libraries and databases do not store MSn data, except for HighChem's commercial Spectral Tree library with currently 2740 spectral trees, mzCloud [35] (a freely available Web interface) with currently 2625 spectral trees, and the open access MassBank database [76] that contains 2.2% MS3 or MS4 spectra. Both HighChem's Spectral Tree library and mzCloud support precursor-ion fingerprinting [25] and are fully integrated with Mass Frontier 7.0."
Ren, W.; Li, Y.; Zuo, R.; Wang, H. J.; Si, N.; Zhao, H. Y.; Bian, B. L. Species‐related difference between limonin and obacunone among five liver microsomes and zebrafish using ultra‐high‐performance liquid chromatography coupled with a LTQ‐Orbitrap mass spectrometer. Rapid Communications in Mass Spectrometry 2014, 28, 2292. "The chromatography system consisted of an autosampler, a diode-array detector, a column compartment and two pumps. Xcalibur, Metworks and Mass Frontier 7.0 software packages were used for data collection and data analysis."
Jin, Y.; Wu, C.-S.; Zhang, J.-L.; Li, Y.-F. A new strategy for the discovery of epimedium metabolites using high-performance liquid chromatography with high resolution mass spectrometry. Analytica Chimica Acta 2013, 768, 111. "HPLC–HRMS data acquired with Xcalibur version 2.0 software were processed using the Mass Frontier™ 6.0 software to construct mass spectral trees. First-stage mass spectral data were used to form the stem, and data-dependent subsequent stage mass spectra were used to form the branches. To convert HRMS and multiple-stage mass spectrometric data from all detected compounds to mass spectral trees data, a total extraction component detection (TECD) algorithm was used to detect components with the setting as follows: tree-branching began at the second MS stage with a trees match factor of 90%. The library of mass spectral trees was built by importing mass spectral trees data of template compounds consisting of parent compounds or predictable metabolites."
Du, F.; Ruan, Q.; Zhu, M.; Xing, J. Detection and characterization of ticlopidine conjugates in rat bile using high-resolution mass spectrometry: applications of various data acquisition and processing tools. Journal of Mass Spectrometry 2013, 48, 413. „...shifts from the parent drug, fragmentation patterns and elemental compositions. In addition, Mass Frontier 6.0 was used in aiding MS/MS spectral interpretation of metabolites.”
Dingemanse, J.; Hoever, P.; Hoch, M.; Treiber, A.; Wagner-Redeker, W.; Miraval, T.; Hopfgartner, G.; Shakeri-Nejad, K. Elucidation of the Metabolic Pathways and the Resulting Multiple Metabolites of Almorexant, a Dual Orexin Receptor Antagonist, in Humans. Drug Metabolism and Disposition 2013. „... 461759 (M7) are given in the supplement (Supplementary Figures 1-10) as well as the structure of the key fragments of ACT-078573 and its metabolites (Supplementary Table 1) suggested by Mass Frontier 6.0 …. This correlation between fragment masses and fragment structures facilitated the interpretation of MSn spectra of unknowns. In several instances the proposed structures and fragmentation pathways were further confirmed by accurate mass.“
Liu, T.; Du, F.; Zhu, F.; Xing, J. Metabolite identification of artemether by data-dependent accurate mass spectrometric analysis using an LTQ-Orbitrap hybrid mass spectrometer in combination with the online hydrogen/deuterium exchange technique. Rapid Communications in Mass Spectrometry 2011, 25, 3303. "The fragmentation predicted by Mass Frontier 6.0 (Thermo Fisher Scientific) was based on general fragmentation rules of the even-electron protonated molecule, allowing for bond cleavage with hydrogen rearrangement and subsequent isomerization and stabilization."
Staack, R.; Hopfgartner, G. New analytical strategies in studying drug metabolism. Analytical and bioanalytical chemistry 2007, 388, 1365. "The products usually assume fragments are even-electron ions and apply known fragmentation rules; usually, therefore, they have difficulties assigning complex rearrangements or odd-electron fragments, which occur more often than expected [40]. With Mass Frontier the user can either select common fragmentation rules and/or search in a library."
Lim, H.-K.; Chen, J.; Sensenhauser, C.; Cook, K.; Subrahmanyam, V. Metabolite identification by data-dependent accurate mass spectrometric analysis at resolving power of 60 000 in external calibration mode using an LTQ/Orbitrap. Rapid Communications in Mass Spectrometry 2007, 21, 1821. „A metabolite identification workflow was developed to utilize chemical formulas from high-resolution accurate mass measurements to confirm structures of product ions of a drug proposed by Mass Frontier, illustrated by identification of structures used to establish lineage of product ions of carvedilol, which later served as a template for identification of its metabolites.”
Suchanova, B.; Sispera, L.; Wsol, V. Liquid chromatography–tandem mass spectrometry in chiral study of amlodipine biotransformation in rat hepatocytes. Analytica Chimica Acta 2006, 573–574, 273. “Acquired product ion spectra of the eight studied metabolites were compared with product ion spectra of knowledge-based predicted metabolites [24] with corresponding masses (generated by Mass Frontier). From the oretically possible structures of metabolites were chosen those in which measured and theoretical product ion spectra matched the best.”
Baldacci, A.; Caslavska, J.; Wey, A. B.; Thormann, W. Identification of new oxycodone metabolites in human urine by capillary electrophoresis–multiple-stage ion-trap mass spectrometry. Journal of Chromatography A 2004, 1051, 273. “Mass spectra for these compounds were predicted up to MS3 (partial prediction of MS4) by computer simulation using the HighChem Mass Frontier version 1.0 software package.”
Hopfgartner, G.; Husser, C.; Zell, M. Rapid screening and characterization of drug metabolites using a new quadrupole–linear ion trap mass spectrometer. Journal of Mass Spectrometry 2003, 38, 138. Spectra interpretation is fairly straightforward, and the use of software tools such as Mass Frontier (HighChem) greatly facilitates this task.


Qu, L., Wang, W., Zeng, D., Lu, Y. and Yin, Z., 2015. Quantitative performance of online SPE-LC coupled to Q-Exactive for the analysis of sofosbuvir in human plasma. RSC Advances, 5(119), pp.98269-98277. "Mass Frontier 7.0 (HighChem, Ltd, Bratislava, Slovakia) was used to obtain the fragmentation pattern and accurate mass of the product ions in positive mode."
Wagner-Redeker, W.; Finsterwald, I.; Dingemanse, J. Validation of an LC-MS/MS method for the quantitative determination of the orexin receptor antagonist almorexant and its four primary metabolites in human plasma. Journal of Chromatography B 2014, 951, 96. "The structure assignments in Fig. 2 were done with the help of Mass Frontier (Thermo Fisher Scientific, Waltham, MA, USA), a software package to support the interpretation of MS/MS spectra."
Cherlet, M.; Gleich, S.; Dewerchin, H.; Nauwynck, H.; Daminet, S.; De Backer, P.; Croubels, S. Quantitative analysis of an anti-viral immune escape compound ML-7 in feline plasma using ultra performance liquid chromatography/electrospray ionization mass spectrometry. Journal of Chromatography B 2012, 905, 118. "According to the Mass Frontier 6.0 software (HighChem, Ltd., Bratislava, Slovakia) this corresponds to the 1,4-diazepine moiety of the components, after protonation and charge site rearrangement (rHc (γ)). This software has a module “Fragments and Mechanisms” which is an expert system providing information about basic fragmentation and rearrangement processes based on literature, starting from a user-supplied chemical structure."

Clinical pharmacology

Dietary Suplements

Kern, S.E., Lorenz, L.M., Lanzarotta, A., Nickum, E.A. and Litzau, J.J., 2016. Isolation and structural characterization of a new tadalafil analog (chloropropanoylpretadalafil) found in a dietary supplement. Journal of Pharmaceutical and Biomedical Analysis. "... from Compound 1 and chloropretadalafil are based on the elucidation of fragment ions in Mass Frontier version 5.1 spectral interpretation software (Thermo Fisher Scientific, San Jose, CA) or based on information available in mzCloud database (HighChem LLC, Slovakia) ..."
Qu, L., Fan, Y., Wang, W., Ma, K. and Yin, Z., 2016. Development, validation and clinical application of an online-SPE-LC-HRMS/MS for simultaneous quantification of phenobarbital, phenytoin, carbamazepine, and its active metabolite carbamazepine 10, 11-epoxide. Talanta, 158, pp.77-88. "For some selected analogues, characteristic MS2 fragment ions obtained from the CID mode were chosen as precursor ions in the MS3 experiment. The MS data interpretation was performed using the Mass Frontier software (version 7.0, HighChem, Slovakia)."


Doping control

Virus, E. D.; Sobolevsky, T. G.; Rodchenkov, G. M. Introduction of HPLC/orbitrap mass spectrometry as screening method for doping control. Journal of Mass Spectrometry 2008, 43, 949. “In our work, possible fragmentation pathways for each doping agent were generated by the expert system software Mass Frontier v. 5.0. Finally, owing to the use of Mass Frontier, proper ions were selected in terms of their selectivity”
Guan, F.; Soma, L. R.; Luo, Y.; Uboh, C. E.; Peterman, S. Collision-Induced Dissociation Pathways of Anabolic Steroids by Electrospray Ionization Tandem Mass Spectrometry. Journal of the American Society for Mass Spectrometry 2006, 17, 477. “Interpretation of product-ion spectra of the anabolic steroids and elucidation of their fragmentation pathways are quite difficult because they do not contain a charge-retaining center such as a nitrogen atom in their molecules and there are several rings in their chemical structures. To overcome this difficulty, Mass Frontier was used in addition to accurate mass measurements and MSn experiments, to aid in the elucidation of fragmentation pathways.”

Food Toxicology

Abernethy, G.A., 2015. Generation of semicarbazide from natural azine development in foods, followed by reaction with urea compounds. Food Additives & Contaminants: Part A, 32(9), pp.1416-1430. "Fragmentation patterns were matched with authentic NBA-SEM where appropriate and tentative identification of other compounds was achieved by comparing the fragments observed with theoretical fragmentation patterns generated by Mass Frontier 5.1 software (HighChem, Bratislava, Slovakia)"
Reilly, C. A.; Henion, F.; Bugni, T. S.; Ethirajan, M.; Stockmann, C.; Pramanik, K. C.; Srivastava, S. K.; Yost, G. S. Reactive Intermediates Produced from the Metabolism of the Vanilloid Ring of Capsaicinoids by P450 Enzymes. Chemical Research in Toxicology 2012, 26, 55. "Interpretation of MSn Spectra Interpretation of MS2 and MS3 spectra obtained for the GSH and BME conjugates of capsaicin, for purposes of structural elucidation, was facilitated by Mass Frontier 4.0 Software"
Li, L.; Low, M.-Y.; Ge, X.; Bloodworth, B. C.; Koh, H.-L. Isolation and structural elucidation of dapoxetine as an adulterant in a health supplement used for sexual performance enhancement. Journal of Pharmaceutical and Biomedical Analysis 2009, 50, 724. "The product ion at m/z 117 (fragmentation 5) was produced by cleaving the C-O bond between C-3 and O atom from the group with m/z 261. These fragments were further confirmed by Mass Frontier™ 5.0 (HighChem, Ltd., Slovak Republic)"

Textil Toxicology

Forensic and Designer drugs

Schmidt, E.M., Franco, M.F., Cuelbas, C.J., Zacca, J.J., de Carvalho Rocha, W.F., Borges, R., de Souza, W., Sawaya, A.C.H.F., Eberlin, M.N. and Correa, D.N., 2015. Characterization of anti-theft devices directly from the surface of banknotes via easy ambient sonic spray ionization mass spectrometry. Science & Justice, 55(5), pp.285-290. "For the management, evaluation and interpretation of ESI(+)–HRMS/MS mass spectral data, Xcalibur 2.1 Software (ThermoFisher Scientific Inc., San Jose, CA, USA) and Thermo Scientific™ High Chem Mass Frontier 7.0 Spectral Interpretation Software were used."
Mueller, D. M.; Rentsch, K. M. Generation of metabolites by an automated online metabolism method using human liver microsomes with subsequent identification by LC-MS (n), and metabolism of 11 cathinones. Analytical and bioanalytical chemistry 2012, 1. "Metabolites were identified using their MS2 and MS3 mass spectra. Methods applied were neutral-loss scans and comparisons of their fragmentation patterns to the parent substances. Raw files were examined both manually and assisted by MassFrontier 7"
Kee, C.-L.; Ge, X.; Koh, H.-L.; Low, M.-Y. Isolation and characterization of propoxyphenyl linked sildenafil and thiosildenafil analogues in health supplements. Journal of Pharmaceutical and Biomedical Analysis 2012, 70, 265. "A proposed fragmentation pathway or these ions is illustrated in Fig. 7 using the Mass Frontier™ 5.0 software (HighChem, Ltd., Slovak Republic). The loss of the 2,6-dimethylpiperazine moiety can be via the cleavage of the sulfonamide bond for propoxyphenyl aildenafil and propoxyphenyl thioaildenafil to give pyrazolopyrimidine-phenyl-SO2 H2+ fragmentation ions at m/z 391 and 407, respectively."
Wissenbach, D.; Meyer, M.; Remane, D.; Philipp, A.; Weber, A.; Maurer, H. Drugs of abuse screening in urine as part of a metabolite-based LC-MSn screening concept. Analytical and Bioanalytical Chemistry 2011, 400, 3481. “Software TF Xcalibur 2.1.0 was used for data acquisition, NIST MS Search 2.0 (National Institute of Standards and Technology, Gaithersburg, MD, USA) for library generation, Mass Frontier (Highchem, Bratislava, Slovakia) for prediction of MS2 and MS3 fragments, and TF ToxID 2.1.1 for target screening in the MS2 screening mode”
Hudson, S.; Ramsey, J.; King, L.; Timbers, S.; Maynard, S.; Dargan, P. I.; Wood, D. M. Use of High-Resolution Accurate Mass Spectrometry to Detect Reported and Previously Unreported Cannabinomimetics in “Herbal High” Products. Journal of Analytical Toxicology 2010, 34, 252. “A fragmentation pathway was generated for the fragment ions m/z 284 and 286 using Mass Frontier software…. The accurate masses recorded were consistent with those of the generated fragment ions.”
Nielen, M. W. F.; Hooijerink, H.; Claassen, F. C.; van Engelen, M. C.; van Beek, T. A. Desorption electrospray ionisation mass spectrometry: A rapid screening tool for veterinary drug preparations and forensic samples from hormone crime investigations. Analytica Chimica Acta 2009, 637, 92. “In the MS3 spectrum of Fig. 4 a loss of water, a second and a third glyco-substructure can be seen, in accordance with the Mass Frontier 5.0 library spectrum of tylosin and previous chemical ionisation results.”