Tools
Mass Spectrometer
Introduction
Mass spectrometry (MS) is a powerful qualitative and quantitative analytical technique used to identify and quantify a wide range of clinically relevant analytes.[1] When coupled with gas or liquid chromatographs, mass spectrometers allow the expansion of analytical capabilities to various clinical applications.[2] In addition, because of its ability to identify and quantify proteins, MS is an essential analytical tool in the field of proteomics.[3]
Most mass spectrometry data are presented in units of the mass-to-charge ratio, or m/z, where m is the molecular weight of the ion (in daltons) and z is the number of charges present on the measured molecule.[4] For small molecules (<1000 Da), there is typically only a single charge; therefore, the m/z value is the same as the mass of the molecular ion.[5] However, when larger molecules such as proteins or peptides are measured, they typically carry multiple ionic charges, and therefore the z value is an integer greater than 1. In these cases, the m/z value will be a fraction of the ion's mass.[6]
Sample preparation is critical to successful MS, particularly when dealing with complex matrices, such as are commonly encountered in clinical chemistry. This typically involves one or more of the following steps: (1) protein precipitation followed by centrifugation or filtration, (2) solid-phase extraction, (3) liquid-liquid extraction, (4) affinity enrichment, or (5) derivatization.[7] Derivatization is the process of chemically modifyingthe target compounds to be more favorably analyzed by MS.[8] Derivatization usually involves the addition of some well-defined functional group.[9] The goals of derivatization vary, depending on the application, but typically include (1) increased volatility, (2) greater thermal stability, (3) modified chromatographic properties, (4) greater ionization efficiency, (5) favorable fragmentation properties, or a combination of these.[10]
Mass spectrometers convert molecules into ions which are then manipulated by electric and magnetic fields.[11] This requires three main components, which includes:
- Ion source: a sample is put into the mass spectrometer, which is then ionized by the apparatus.[12]
- Mass analyzer: ions are sorted in the device based on their mass-to-charge ratio (m/z).
- Detector: ions are measured and displayed on the mass spectrum chart.
Atoms and molecules must first be ionized before they can be accelerated through the mass spectrometer and detected.[13] The sample molecule entered into the mass spectrometer will first get a positive charge from an ionization source. This positive charge is achieved by removing a valence electron. Protons can also be added to create a positive electrical charge. Next, the ionized molecule breaks apart into smaller fragments, then separated according to their mass-to-charge ratio in the mass analyzer.[1] Of note, only the cationic fragments are separated. The neutral species in the mass spectrometer goes undetected because it can be 1) absorbed by the apparatus or 2) removed by a vacuum. After the ions are separated, the detector will quantify the ions.[11]
A chart will be generated to analyze the mass spectrometer's results. The mass-to-charge ratio (m/z) is on the "x-axis," while the relative intensity is on the "y-axis." [12] For a given sample, the most abundant ion in the sample molecule is known as the base peak.[14] This ion is set to 100% on the y-axis for its relative intensity, and all the remaining ion peaks are generated relative to this value. The molecular ion peak is known as the parent peak because it corresponds to the molecular weight of the sample.[15] For example, if the specimen in the mass spectrometer was hexane, the m/z would be 86 since the molecular weight of hexane is 86 g/mol. Additionally, if there is a peak at m/z = 87, this would be classified as the m+1 peak because all atoms have various isotopes.[11]
Specimen Requirements and Procedure
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Specimen Requirements and Procedure
Prior to using the mass spectrometer, a sample must be prepared for it to be ionized. Thus, samples are either in the liquid or gaseous phase by utilizing chromatography techniques. The two types of chromatography procedures that are used to prepare the sample are gas chromatography and liquid chromatography.[16]
Gas Chromatography
Gas chromatography separates components of a mixture of gases and filters the passage of these molecules based on physical characteristics like shape, size, molecular weight, and boiling point. A sample is diluted and vaporized in the chromatograph, where it is separated. After separation, the gases enter the mass spectrometer for analysis. Notably, a gas chromatography sample must be volatile, meaning it must enter the gas phase so it does not break down while in the mass spectrometer apparatus.[17]
Liquid Chromatography
Liquid chromatography separates samples based on interactions with the mobile and stationary phases. This can be based on polarities, meaning that if a component of the specimen has a different polarity compared to the mobile phase, it will migrate down the chromatograph column faster. The sample is separated into bands into individual components that can be further analyzed in mass spectrometry.[18]
Other techniques used for sample preparation include electrospray ionization, which uses high voltages to separate out components, and fast atom bombardment, which uses a beam to generate ions from a solid phase.[19][20]
The types of samples that can be analyzed within mass spectrometry include proteins, nucleic acids, lipids, and fatty acids, to name a few.[21]
Testing Procedures
In mass spectrometry, the following components are used to test the sample for analysis.
Ionization
During ionization, the atoms are ionized by removing an electron to give off a positive ion known as a cation. Mass spectrometers only work with positive ions. Cations are formed regardless of the present state of the atoms. For example, this is true even if there is initially a negative ion in the sample, such as fluoride, or an element that does not form ions, such as neon.[22] Inside the mass spectrometer, an electrical field is generated that gives off electrons. These electrons will return to the electron trap, forming collisions to knock off the electrons to create cations.[23]
The most common form of ionization used in GC/MS is electron ionization (EI). This method requires a source of electrons in the form of a filament to which an electric potential is applied, typically at 70 eV.[24] The molecules in the source are bombarded with high-energy electrons, resulting in the formation of charged molecular ions and fragments. Molecules break down into characteristic fragments according to their molecular structure.[25] The ions formed and their relative proportions are reproducible and can be used for qualitative identification of the compound.[26]
Unlike electron ionization (EI) in GC/MS, most LC/MS ionization techniques are conducted at atmospheric pressure. Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are “soft” ionization techniques that leave the molecular ion largely intact in the source.[27] Many LC/MS techniques employ technologies after the source, in the mass analyzer, to fragment molecules and generate the daughter or fragment ions used in identification.[28] However, ionization techniques in LC/MS produce fragments and, therefore, mass spectra that are somewhat less reproducible between instruments than EI used in GC/MS.[29]
Electrospray ionization uses a combination of voltage, heat, and air to produce successively smaller droplets from the liquid, eluting off a chromatographic column.[30] The continuous loss of solvent concentrates these droplets, dramatically increasing charge per unit volume. Ions accumulated at the droplet surface desorb from the liquid into the gas phase, allowing these gas phase ions to enter into the mass spectrometer for analysis.[31] In addition, complete evaporation of the solvent liberates large ions, such as proteins, producing the necessary gas phase ions for analysis.[32]
Atmospheric pressure chemical ionization produces ions by using a combination of heat to completely vaporize the sample and plasma produced by an electrical discharge, commonly referred to as a corona discharge.[33] The corona discharge ionizes the evaporated solvent, and through physical interaction with gaseous sample components (including the analytes of interest), the formation of negative or positive ions occurs.[34]
Acceleration
All ions will undergo acceleration to have the same amount of kinetic energy. Cations will pass through slits in the mass spectrometer apparatus and accelerate into the ion beam. This allows the mass analyzer to start separating the ions based on the mass-to-charge ratio.[35]
Deflection
A magnetic field will deflect cations based on their mass and charge. Mass and deflection are inversely proportional, while charge and deflection are directly proportional. Therefore, if an ion is of lesser mass, it will get deflected more in the apparatus. If an ion has a greater positive charge compared to its counterparts, then it will get deflected more, as well.[36]
Thus, the deflection principles will allow the mass-to-charge ratio to be determined by the apparatus. The mass-to-charge ratio is denoted by m/z. If an ion has a mass of 120 and a charge of 3+, the ratio would be 40. Of note, it is important to remember that most ions that pass through the mass spectrometer have a charge of 1+, so almost all the ions will have a mass (or molecular weight) equivalent to the m/z value.[37]
Detection
A detector in the mass spectrometer apparatus will quantify the ions and remove certain ones. Positive ions are detected by the apparatus, while neutral ions will be removed by the vacuum.[38] The most common means of detecting ions employs an electron multiplier.[39] In this detector, a series of dynodes with increasing potentials are linked. When ions strike the first dynode surface, electrons are emitted. These electronsare attracted to the next dynode, where more secondary electrons are emitted due to the higher potential of subsequent dynodes. A cascade of electrons is formed by the end of the chain of dynodes, resulting in overall signal amplification on the order of 1 million or greater.[40]
Vacuum
Mass spectrometers operate at low pressure, which creates a vacuum effect as there is less probability that ions will collide with one another in the apparatus. This then allows for the proper separation of cations with the neutral ions as the vacuum extracts the neutral molecules.[41]
Interfering Factors
The main interference factors that can arise with mass spectrometry occur during sample preparation and measuring separated ions in the spectrometer. Interference can occur due to inaccurate sample handling when acquiring from patients or improper quality control.[42] Interference alters the concentration of the molecules, which can result in the inaccuracy of the mass spectrometer graph due to potential contaminants or other ions appearing.[43]
Results, Reporting, and Critical Findings
Mass spectrometry produces results for the mass-to-charge ratio of ions in a compound.[2] The results are reproduced on a graph known as a mass spectrum, which plots the relative abundance of ions versus the mass-to-charge ratio.[3] The spectra showcase elements and isotopes to configure a given compound's chemical identity and structure.[14]
It is important to analyze the graph to deduce the structural quality of the compound based on the mass spectrometer. The graph has three main components and an additional component depending on the isotopes present in the sample, which are relevant in figuring out the structure:
- Molecular Ion Peak (or Parent Peak): This is the second-highest peak that corresponds directly to the compound in question. The m/z ratio directly correlates to the molecular weight. For example, if hexane is the compound, then the m/z ratio is 86 since that is the molecular weight.[44]
- Base Peak: This is the ion with the highest relative abundance in the compound out of all the ions in the given sample. The relative intensity of this ion is set to 100%, and all other ion peaks are set relative to this value.[45]
- M+1 Peak: This is a smaller peak that directly corresponds to an isotope in the sample. If the molecular weight of the specimen is 96 g/mol, the m/z ratio is 96. Thus, the m+1 peak is at an m/z of 97. It might be confusing how it is possible for an ion to have a mass greater than the compound in question, but this is because there are many isotopes of elements, such as carbon and hydrogen, which can result in an m+1 peak.[46]
- M+2 Peak: This is another small peak similar to the m+1 peak. Certain elements, such as chlorine and oxygen, have multiple isotopes, which is why these elements in a given compound can result in an m+2 peak.[46]
Clinical Significance
Mass spectrometry is applicable across diverse fields, including forensic toxicology, metabolomics, proteomics, pharma/biopharma, and clinical research. Specific applications of mass spectrometry include drug testing and discovery, food contamination detection, pesticide residue analysis, isotope ratio determination, protein identification, and carbon dating.[47]
Applications of Mass Spectrometry in the Diagnosis of Disease
Mass spectrometers are primarily used in clinical settings to diagnose diseases due to biomarkers. Biomarkers are utilized in diagnoses, prognoses, and treatment.[48] For example, the enzyme amylase can be used as a biomarker for pancreatitis in disease diagnosis. Similarly, natriuretic peptides are monitored in patients with cardiovascular diseases to predict patient outcomes. To monitor the efficacy of certain therapy, mass spectrometry can be used to see the metabolic profile of pharmacologic agents.[49]
Mass spectrometers can measure biomarkers, ranging in size from small molecules to large macromolecules.[50] The principle of mass spectrometers also applies to human body samples such as plasma and serum blood, urine, saliva, sweat and skin secretions, and more.[2] Using liquid or gas chromatography allows for biomarkers to be separated and analyzed in smaller pieces, which optimizes the sensitivity and specificity of the spectrometer. Thus, mass spectrometers thereby improve clinical decision-making.[6]
To diagnose disease, mass spectrometers focus on analyzing a sample and its biomarker profile. Of note, two critical biomarkers are proteins and lipids.[13] In earlier examples, it was stated that enzymes, which are proteins, can be used as a way to detect diseases. Similarly, a lipid panel has often been used to diagnose diseases such as metabolic syndrome.[1]
If the biomarker is a protein, we can use the principles of proteomics and apply them to mass spectrometry.[13] Mass spectrometry has been used to quantify differences between two biological states of proteomes, a set of proteins produced in a specific organism. A protein sample is placed into the spectrometer, and the mass of the individual components of the protein are tagged based on the isotopes generated through spectral analyses.[2] The mass spectrometer is useful in this setting because it generates spectral data for proteomes, which allows the analysis of proteins in the human body in urine, serum, and more.[3]
If the biomarker is a lipid, we can use the principles of lipidomics to generate a clinical profile for the patient using mass spectrometry, as well.[21] Lipidomics consists of the lipid profile and set of reactions generated within biology. Lipids are utilized for energy storage and assist in the endocrine regulation of the body system.[51] Mass spectrometry has been used to characterize masses of important ingredients that are part of lipid oxidation reactions. This has helped to quantify the various molecules that are part of lipid reactions and, thus, their biological properties within the human body.[52]
Applications of Mass Spectrometry in COVID-19
During the peak of the coronavirus pandemic, many countries were hindered by inadequate testing due to supply chain shortages and inconsistencies in mass-produced testing kits. Clinical laboratories thus created a method to use mass spectrometry. Nasal swab samples of patients were applied to mass spectrometers, and the pattern generated by the spectrum was used to categorize patients if they were COVID-19 positive or COVID-19 negative.[53]
Applications of Mass Spectrometry in Pharmaceuticals
Mass spectrometry is relevant in analyzing pharmaceutical drugs. The ionization that is performed in the apparatus helps differentiate the molecules that create the drugs. This is essential because it enables faster and more accurate screenings in the clinical analysis of patient samples.[54]
Applications of Mass Spectrometry in the Analysis of Glycans
Oligosaccharides are molecules formed by the association of several monosaccharides linked through glycosidic bonds. Determining the complete structure of oligosaccharides is more complex than that of proteins or oligonucleotides. It involves the determination of additional components as a consequence of the isomeric nature of monosaccharides and their capacity to form linear or branched oligosaccharides.[55] Knowing the structure of an oligosaccharide requires not only the determination of its monosaccharide sequence and its branching pattern but also the isomer position and the anomeric configuration of each of its glycosidic bonds.[56] Advances in glycobiology involve a comprehensive study of the structure, biosynthesis, and biology of sugars and saccharides. Mass spectrometry (MS) is emerging as an enabling technology in the field of glycomics and glycobiology.[57]
Applications of Mass Spectrometry in the Analysis of Oligonucleotides
Oligonucleotides (DNA or RNA) are linear polymers of nucleotides. These are composed of a nitrogenous base, a ribose sugar, and a phosphate group.[58] Oligonucleotides may undergo several natural covalent modifications, which are commonly present in tRNA and rRNA, or unnatural ones resulting from reactions with exogenous compounds.[59] Mass spectrometry plays a vital role in identifying these modifications and determining their structure as well as their position in the oligonucleotide. It not only allows the determination of the molecular weight of oligonucleotides but also, directly or indirectly, the determination of their sequences.[60]
Applications of Mass spectrometry in Environmental Analysis
Drinking water testing, pesticide screening and quantitation, soil contamination assessment, carbon dioxide, and pollution monitoring, and trace elemental analysis of heavy metals leaching.[61]
Applications of Mass Spectrometry in Forensic Analysis
Analysis of trace evidence (e.g., fibers in carpet, polymers in paint), arson investigation (e.g., fire accelerant), confirmation of drug abuse, and identification of explosive residues (bombing investigation).[62]
Quality Control and Lab Safety
When in the lab, it is important to use caution during the process of sample preparation before placing the compound in the mass spectrometer for analysis. For example, using the proper measuring tools for accuracy during chromatography is essential.[63] If quality control is not used, resultant peaks may form in the mass spectrum, which does not correspond to ions within the sample.[64]
Operating the mass spectrometer requires safety to be taken into consideration. The mass spectrometer apparatus can have high temperatures, which can result in burns. Thus, it is important not to touch any part of the apparatus while the spectral data is generated. Additionally, ionization occurs within the device, so it is essential to be cautious when running a mass spectrometer. Lastly, the samples placed in the spectrometer could be hazardous upon exposure to the skin or inhalation.[65] Thus, wearing the appropriate personal protective equipment, such as safety glasses, long pants, closed-toed shoes, a long lab coat, and gloves, is highly suggested.[66]
Enhancing Healthcare Team Outcomes
Interprofessional communication is required when using mass spectrometers. For example, if a patient has ingested a certain unknown compound and presents it to the emergency department, lab technicians and pathologists can take the patient's sample and acquire results for the components present in the compound. This allows for support from individuals in laboratory settings to healthcare workers, such as nurses and other physicians, who may be present in the hospital or clinic settings. Physicians in the emergency room can contribute to the interprofessional environment by discussing the patient's history and physical examination outcomes to help further narrow down the compounds in the patient's sample.
References
Király M,Dalmadiné Kiss B,Vékey K,Antal I,Ludányi K, [Mass spectrometry: past and present]. Acta pharmaceutica Hungarica. 2016 [PubMed PMID: 27295872]
Matthiesen R,Bunkenborg J, Introduction to mass spectrometry-based proteomics. Methods in molecular biology (Clifton, N.J.). 2013 [PubMed PMID: 23666720]
Zhang G,Annan RS,Carr SA,Neubert TA, Overview of peptide and protein analysis by mass spectrometry. Current protocols in protein science. 2010 Nov; [PubMed PMID: 21104985]
Level 3 (low-level) evidenceUrban PL, Quantitative mass spectrometry: an overview. Philosophical transactions. Series A, Mathematical, physical, and engineering sciences. 2016 Oct 28 [PubMed PMID: 27644965]
Level 3 (low-level) evidenceSugai T, Mass and Charge Measurements on Heavy Ions. Mass spectrometry (Tokyo, Japan). 2017; [PubMed PMID: 29302406]
Domon B,Aebersold R, Mass spectrometry and protein analysis. Science (New York, N.Y.). 2006 Apr 14 [PubMed PMID: 16614208]
Wilschefski SC, Baxter MR. Inductively Coupled Plasma Mass Spectrometry: Introduction to Analytical Aspects. The Clinical biochemist. Reviews. 2019 Aug:40(3):115-133. doi: 10.33176/AACB-19-00024. Epub [PubMed PMID: 31530963]
Finoulst I,Pinkse M,Van Dongen W,Verhaert P, Sample preparation techniques for the untargeted LC-MS-based discovery of peptides in complex biological matrices. Journal of biomedicine & biotechnology. 2011 [PubMed PMID: 22203783]
Guerrasio R,Haberhauer-Troyer C,Steiger M,Sauer M,Mattanovich D,Koellensperger G,Hann S, Measurement uncertainty of isotopologue fractions in fluxomics determined via mass spectrometry. Analytical and bioanalytical chemistry. 2013 Jun; [PubMed PMID: 23559335]
Vilbaste M,Tammekivi E,Leito I, Uncertainty contribution of derivatization in gas chromatography/mass spectrometric analysis. Rapid communications in mass spectrometry : RCM. 2020 Aug 30; [PubMed PMID: 31845399]
Haag AM, Mass Analyzers and Mass Spectrometers. Advances in experimental medicine and biology. 2016; [PubMed PMID: 27975216]
Level 3 (low-level) evidenceOlshina MA,Sharon M, Mass Spectrometry: A Technique of Many Faces. Quarterly reviews of biophysics. 2016 Jan; [PubMed PMID: 28100928]
Bantscheff M,Schirle M,Sweetman G,Rick J,Kuster B, Quantitative mass spectrometry in proteomics: a critical review. Analytical and bioanalytical chemistry. 2007 Oct; [PubMed PMID: 17668192]
Alexandrov T,Chernyavsky I,Becker M,von Eggeling F,Nikolenko S, Analysis and interpretation of imaging mass spectrometry data by clustering mass-to-charge images according to their spatial similarity. Analytical chemistry. 2013 Dec 3 [PubMed PMID: 24180335]
Level 3 (low-level) evidenceBuchberger AR,DeLaney K,Johnson J,Li L, Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights. Analytical chemistry. 2018 Jan 2 [PubMed PMID: 29155564]
Bourgogne E,Wagner M, [Sample preparation and bioanalysis in mass spectrometry]. Annales de biologie clinique. 2015 Jan-Feb; [PubMed PMID: 25582719]
Fothergill WT, Gas chromatography. Technique. Proceedings of the Royal Society of Medicine. 1968 May; [PubMed PMID: 5655250]
Rappold BA, Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part I-Development. Annals of laboratory medicine. 2022 Mar 1; [PubMed PMID: 34635606]
Meher AK,Chen YC, Electrospray Modifications for Advancing Mass Spectrometric Analysis. Mass spectrometry (Tokyo, Japan). 2017; [PubMed PMID: 28573082]
Hemling ME, Fast atom bombardment mass spectrometry and its application to the analysis of some peptides and proteins. Pharmaceutical research. 1987 Feb; [PubMed PMID: 3334162]
Züllig T,Köfeler HC, HIGH RESOLUTION MASS SPECTROMETRY IN LIPIDOMICS. Mass spectrometry reviews. 2021 May; [PubMed PMID: 32233039]
Lin JL,Chu ML,Chen CH, A portable multiple ionization source biological mass spectrometer. The Analyst. 2020 May 18; [PubMed PMID: 32186555]
Huang MZ,Cheng SC,Cho YT,Shiea J, Ambient ionization mass spectrometry: a tutorial. Analytica chimica acta. 2011 Sep 19 [PubMed PMID: 21819855]
Maciel EVS,Pereira Dos Santos NG,Vargas Medina DA,Lanças FM, Electron ionization mass spectrometry: Quo vadis? Electrophoresis. 2022 Aug; [PubMed PMID: 35531989]
Margolin Eren KJ,Elkabets O,Amirav A, A comparison of electron ionization mass spectra obtained at 70 eV, low electron energies, and with cold EI and their NIST library identification probabilities. Journal of mass spectrometry : JMS. 2020 Dec [PubMed PMID: 32996658]
Famiglini G,Palma P,Termopoli V,Cappiello A, The history of electron ionization in LC-MS, from the early days to modern technologies: A review. Analytica chimica acta. 2021 Jul 4 [PubMed PMID: 34049632]
Commisso M,Anesi A,Dal Santo S,Guzzo F, Performance comparison of electrospray ionization and atmospheric pressure chemical ionization in untargeted and targeted liquid chromatography/mass spectrometry based metabolomics analysis of grapeberry metabolites. Rapid communications in mass spectrometry : RCM. 2017 Feb 15 [PubMed PMID: 27935129]
Tian H,Bai J,An Z,Chen Y,Zhang R,He J,Bi X,Song Y,Abliz Z, Plasma metabolome analysis by integrated ionization rapid-resolution liquid chromatography/tandem mass spectrometry. Rapid communications in mass spectrometry : RCM. 2013 Sep 30; [PubMed PMID: 23943328]
Berisha A,Dold S,Guenther S,Desbenoit N,Takats Z,Spengler B,Römpp A, A comprehensive high-resolution mass spectrometry approach for characterization of metabolites by combination of ambient ionization, chromatography and imaging methods. Rapid communications in mass spectrometry : RCM. 2014 Aug 30 [PubMed PMID: 25559448]
Level 3 (low-level) evidenceTycova A,Prikryl J,Kotzianova A,Datinska V,Velebny V,Foret F, Electrospray: More than just an ionization source. Electrophoresis. 2021 Jan [PubMed PMID: 32841405]
Wilm M, Principles of electrospray ionization. Molecular & cellular proteomics : MCP. 2011 Jul [PubMed PMID: 21742801]
Wilm M, Principles of electrospray ionization. Molecular & cellular proteomics : MCP. 2011 May 19 [PubMed PMID: 21597042]
Pitman CN,LaCourse WR, Desorption atmospheric pressure chemical ionization: A review. Analytica chimica acta. 2020 Sep 15 [PubMed PMID: 32892934]
Byrdwell WC, Atmospheric pressure chemical ionization mass spectrometry for analysis of lipids. Lipids. 2001 Apr; [PubMed PMID: 11383683]
Level 3 (low-level) evidenceLee JK,Banerjee S,Nam HG,Zare RN, Acceleration of reaction in charged microdroplets. Quarterly reviews of biophysics. 2015 Nov; [PubMed PMID: 26537403]
Nier KA, Dempster [PubMed PMID: 30900786]
Budzikiewicz H,Grigsby RD, Mass spectrometry and isotopes: a century of research and discussion. Mass spectrometry reviews. 2006 Jan-Feb [PubMed PMID: 16134128]
Elliott AG,Merenbloom SI,Chakrabarty S,Williams ER, Single Particle Analyzer of Mass: A Charge Detection Mass Spectrometer with a Multi-Detector Electrostatic Ion Trap. International journal of mass spectrometry. 2017 Mar; [PubMed PMID: 29129967]
Shan L,Gao H,Zhang J,Li W,Su Y,Guo Y, Plasma and serum exosome markers analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry coupled with electron multiplier. Talanta. 2022 Sep 1 [PubMed PMID: 35623246]
Tsybin YO,Witt M,Baykut G,Håkansson P, Electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry in the electron energy range 0-50 eV. Rapid communications in mass spectrometry : RCM. 2004 [PubMed PMID: 15282786]
Guo C,Diao Z,Liu J,Yang B,Zhang J, Quantification and evaluation of ion transmission efficiency in two-stage vacuum chamber miniature mass spectrometer. Journal of mass spectrometry : JMS. 2022 Mar; [PubMed PMID: 35229406]
Keller BO,Sui J,Young AB,Whittal RM, Interferences and contaminants encountered in modern mass spectrometry. Analytica chimica acta. 2008 Oct 3; [PubMed PMID: 18790129]
Level 3 (low-level) evidenceKim BK,Gwon MR,Kang WY,Lee IK,Lee HW,Seong SJ,Cho S,Yoon YR, Rapid Interference-free Analysis of β-Lapachone in Clinical Samples Using Liquid Chromatography-Mass Spectrometry for a Pharmacokinetic Study in Humans. Analytical sciences : the international journal of the Japan Society for Analytical Chemistry. 2021 Aug 10; [PubMed PMID: 33390413]
Goraczko AJ, Molecular mass and location of the most abundant peak of the molecular ion isotopomeric cluster. Journal of molecular modeling. 2005 Sep; [PubMed PMID: 15928922]
Steeves JB,Gagne HM,Buel E, Normalization of residual ions after removal of the base peak in electron impact mass spectrometry. Journal of forensic sciences. 2000 Jul; [PubMed PMID: 10914589]
Grange AH,Donnelly JR,Sovocool GW,Brumley WC, Determination of elemental compositions from mass peak profiles of the molecular ion (m) and the m 1 and m 2 ions. Analytical chemistry. 1996 Feb 1; [PubMed PMID: 21619089]
Zhang XW,Li QH,Xu ZD,Dou JJ, Mass spectrometry-based metabolomics in health and medical science: a systematic review. RSC advances. 2020 Jan 16; [PubMed PMID: 35497733]
Level 3 (low-level) evidenceFurlani IL,da Cruz Nunes E,Canuto GAB,Macedo AN,Oliveira RV, Liquid Chromatography-Mass Spectrometry for Clinical Metabolomics: An Overview. Advances in experimental medicine and biology. 2021 [PubMed PMID: 34628633]
Level 3 (low-level) evidenceHeaney LM,Jones DJ,Suzuki T, Mass spectrometry in medicine: a technology for the future? Future science OA. 2017 Aug [PubMed PMID: 28884010]
Carneiro G,Radcenco AL,Evaristo J,Monnerat G, Novel strategies for clinical investigation and biomarker discovery: a guide to applied metabolomics. Hormone molecular biology and clinical investigation. 2019 Jan 17 [PubMed PMID: 30653466]
Han X,Yang K,Gross RW, Multi-dimensional mass spectrometry-based shotgun lipidomics and novel strategies for lipidomic analyses. Mass spectrometry reviews. 2012 Jan-Feb; [PubMed PMID: 21755525]
Del Carmen Piqueras M, Utility of Moderate and High-Resolution Mass Spectrometry for Class-Specific Lipid Identification and Quantification. Methods in molecular biology (Clifton, N.J.). 2017 [PubMed PMID: 28660576]
SoRelle JA,Patel K,Filkins L,Park JY, Mass Spectrometry for COVID-19. Clinical chemistry. 2020 Nov 1; [PubMed PMID: 32956447]
Loos G,Van Schepdael A,Cabooter D, Quantitative mass spectrometry methods for pharmaceutical analysis. Philosophical transactions. Series A, Mathematical, physical, and engineering sciences. 2016 Oct 28; [PubMed PMID: 27644982]
Zaia J, Mass spectrometry and glycomics. Omics : a journal of integrative biology. 2010 Aug [PubMed PMID: 20443730]
Level 3 (low-level) evidenceWuhrer M, Glycomics using mass spectrometry. Glycoconjugate journal. 2013 Jan [PubMed PMID: 22532006]
Leymarie N,Zaia J, Effective use of mass spectrometry for glycan and glycopeptide structural analysis. Analytical chemistry. 2012 Apr 3; [PubMed PMID: 22360375]
Level 3 (low-level) evidenceCrain PF,McCloskey JA, Applications of mass spectrometry to the characterization of oligonucleotides and nucleic acids. Current opinion in biotechnology. 1998 Feb [PubMed PMID: 9503584]
Level 3 (low-level) evidenceBasiri B,Bartlett MG, LC-MS of oligonucleotides: applications in biomedical research. Bioanalysis. 2014 Jun [PubMed PMID: 25046052]
Meng Z,Simmons-Willis TA,Limbach PA, The use of mass spectrometry in genomics. Biomolecular engineering. 2004 Jan [PubMed PMID: 14715314]
Hernández F,Sancho JV,Ibáñez M,Abad E,Portolés T,Mattioli L, Current use of high-resolution mass spectrometry in the environmental sciences. Analytical and bioanalytical chemistry. 2012 May; [PubMed PMID: 22362279]
Hoffmann WD,Jackson GP, Forensic Mass Spectrometry. Annual review of analytical chemistry (Palo Alto, Calif.). 2015 [PubMed PMID: 26070716]
Masson P, Quality control techniques for routine analysis with liquid chromatography in laboratories. Journal of chromatography. A. 2007 Jul 27; [PubMed PMID: 17418222]
Level 2 (mid-level) evidenceCooper PJ,Charnock DJ,Taylor MJ, The prevalence of bulimia nervosa. A replication study. The British journal of psychiatry : the journal of mental science. 1987 Nov [PubMed PMID: 3446313]
Bonnel D,Stauber J, Applications of Mass Spectrometry Imaging for Safety Evaluation. Methods in molecular biology (Clifton, N.J.). 2017; [PubMed PMID: 28748461]
Cornish NE, Anderson NL, Arambula DG, Arduino MJ, Bryan A, Burton NC, Chen B, Dickson BA, Giri JG, Griffith NK, Pentella MA, Salerno RM, Sandhu P, Snyder JW, Tormey CA, Wagar EA, Weirich EG, Campbell S. Clinical Laboratory Biosafety Gaps: Lessons Learned from Past Outbreaks Reveal a Path to a Safer Future. Clinical microbiology reviews. 2021 Jun 16:34(3):e0012618. doi: 10.1128/CMR.00126-18. Epub 2021 Jun 9 [PubMed PMID: 34105993]