Tandem mass spectrometry
- 1 Instrumentation
- 2 Fragmentation
- 2.1 In-source fragmentation
- 2.2 Collision-induced dissociation
- 2.3 Electron capture and transfer methods
- 2.4 Photodissociation
- 2.5 Surface induced dissociation
- 3 Quantitative proteomics
- 4 Applications
- 5 See also
- 6 References
- 7 Bibliography
- 8 External links
For tandem mass spectrometry in space, the different elements are often noted in shorthand. Multiple stages of mass analysis separation can be accomplished with individual mass spectrometer elements separated in space or using a single mass spectrometer with the MS steps separated in time.
Tandem in space
In tandem mass spectrometry in space, the separation elements are physically separated and distinct, although there is a physical connection between the elements to maintain high vacuum. These elements can be sectors, transmission quadrupole, or time-of-flight. When using multiple quadrupoles, they can act as both mass analyzers and collision chambers.
- Q – Quadrupole mass analyzer
- q – Radio frequency collision quadrupole
- TOF – Time-of-flight mass analyzer
- B – Magnetic sector
- E – Electric sector
The notation can be combined to indicate various hybrid instrument, for example
- QqQ – Triple quadrupole mass spectrometer
- QTOF – Quadrupole time-of-flight mass spectrometer (also QqTOF)
- BEBE – Four-sector (reverse geometry) mass spectrometer
Tandem in time
By doing tandem mass spectrometry in time, the separation is accomplished with ions trapped in the same place, with multiple separation steps taking place over time. A quadrupole ion trap or FTMS instrument can be used for such an analysis. Trapping instruments can perform multiple steps of analysis, which is sometimes referred to as MSn (MS to the n). Often the number of steps, n, is not indicated, but occasionally the value is specified; for example MS3 indicates three stages of separation. Tandem in time MS instruments do not use the modes described next, but typically collect all of the information from a precursor ion scan and a parent ion scan of the entire spectrum. Each instrumental configuration utilizes a unique mode of mass identification.
Tandem in space MS/MS modes
When tandem MS is performed with an in space design, the instrument must operate in one of a variety of modes. There are a number of different tandem MS/MS experiments and each mode has its own applications and offer their own information. Tandem MS in space uses the coupling of two instrument components which measure the same mass spectrum range but with a controlled fractionation between them in space, while tandem MS in time involves the use of an ion trap.
There are four main scan experiments possible using MS/MS: precursor ion scan, product ion scan, neutral loss scan, and selected reaction monitoring.
For a precursor ion scan, the product ion is selected in the second mass analyzer, and the precursor masses are scanned in the first mass analyzer. Note that precursor ion is synonymous with parent ion and product ion with daughter ion; however the use of these anthropomorphic terms is discouraged.
In a product ion scan, a precursor ion is selected in the first stage, allowed to fragment and then all resultant masses are scanned in the second mass analyzer and detected in the detector that is positioned after the second mass analyzer. This experiment is commonly performed to identify transitions used for quantification by tandem MS.
In a neutral loss scan, the first mass analyzer scans all the masses. The second mass analyzer also scans, but at a set offset from the first mass analyzer. This offset corresponds to a neutral loss that is commonly observed for the class of compounds. In a constant-neutral-loss scan, all precursors that undergo the loss of a specified common neutral are monitored. To obtain this information, both mass analyzers are scanned simultaneously, but with a mass offset that correlates with the mass of the specified neutral. Similar to the precursor-ion scan, this technique is also useful in the selective identification of closely related class of compounds in a mixture.
In selected reaction monitoring, both mass analyzers are set to a selected mass. This mode is analogous to selected ion monitoring for MS experiments. A selective analysis mode, which can increase sensitivity.
Fragmentation of gas-phase ions is essential to tandem mass spectrometry and occurs between different stages of mass analysis. There are many methods used to fragment the ions and these can result in different types of fragmentation and thus different information about the structure and composition of the molecule.
Often, the ionization process is sufficiently violent to leave the resulting ions with sufficient internal energy to fragment within the mass spectrometer. If the product ions persist in their non-equilibrium state for a moderate amount of time before auto-dissociation this process is called metastable fragmentation. Nozzle-skimmer fragmentation refers to the purposeful induction of in-source fragmentation by increasing the nozzle-skimmer potential on usually electrospray based instruments. Although in-source fragmentation allows for fragmentation analysis, it is not technically tandem mass spectrometry unless metastable ions are mass analyzed or selected before auto-dissociation and a second stage of analysis is performed on the resulting fragments. In-source fragmentation is often used in addition to tandem mass spectrometry (with post-source fragmentation) to allow for two steps of fragmentation in a pseudo MS3-type of experiment.
Post-source fragmentation is most often what is being used in a tandem mass spectrometry experiment. Energy can also be added to the ions, which are usually already vibrationally excited, through post-source collisions with neutral atoms or molecules, the absorption of radiation, or the transfer or capture of an electron by a multiply charged ion. Collision-induced dissociation (CID), also called collisionally activated dissociation (CAD), involves the collision of an ion with a neutral atom or molecule in the gas phase and subsequent dissociation of the ion. For example, consider
where the ion AB+ collides with the neutral species M and subsequently breaks apart. The details of this process are described by collision theory.
Electron capture and transfer methods
The energy released when an electron is transferred to or captured by a multiply charged ion can induce fragmentation.
Electron capture dissociation
for a multiply protonated molecule M.
Electron transfer dissociation
Adding an electron through an ion-ion reaction is called electron transfer dissociation (ETD). Similar to electron-capture dissociation, ETD induces fragmentation of cations (e.g. peptides or proteins) by transferring electrons to them. It was invented by Donald F. Hunt, Joshua Coon, John E. P. Syka and Jarrod Marto at the University of Virginia.
where A is the anion.
ETD cleaves randomly along the peptide backbone (c and z ions) while side chains and modifications such as phosphorylation are left intact. The technique only works well for higher charge state ions (z>2), however relative to collision-induced dissociation (CID), ETD is advantageous for the fragmentation of longer peptides or even entire proteins. This makes the technique important for top-down proteomics. Much like ECD, ETD is effective for peptides with modifications such as phosphorylation.
Electron-transfer and higher-energy collision dissociation (EThcD) is a combination ETD and HCD where the peptide precursor is initially subjected to an ion/ion reaction with fluoranthene anions in a linear ion trap, which generates c- and z-ions. In the second step HCD all-ion fragmentation is applied to all ETD derived ions to generate b- and y- ions prior to final analysis in the orbitrap analyzer. This method employs dual fragmentation to generate ion- and thus data-rich MS/MS spectra for peptide sequencing and PTM localization.
Negative electron transfer dissociation
Electron-detachment dissociation (EDD) is a method for fragmenting anionic species in mass spectrometry. It serves as a negative counter mode to electron capture dissociation. Negatively charged ions are activated by irradiation with electrons of moderate kinetic energy. The result is ejection of electrons from the parent ionic molecule, which causes dissociation via recombination.
where represents the photon absorbed by the ion. Ultraviolet lasers can be used, but can lead to excessive fragmentation of biomolecules.
Infrared multiphoton dissociation
Infrared photons will heat the ions and cause dissociation if enough of them are absorbed. This process is called infrared multiphoton dissociation (IRMPD) and is often accomplished with a carbon dioxide laser and an ion trapping mass spectrometer such as a FTMS.
Blackbody infrared radiative dissociation
Blackbody radiation can be used for photodissociation in a technique known as blackbody infrared radiative dissociation (BIRD). In the BIRD method, the entire mass spectrometer vacuum chamber is heated to create infrared radiation. BIRD uses the light from black body radiation to thermally (vibrationally) excite the ions until a bond breaks. This is similar to infrared multiphoton dissociation with the exception of the source of radiation. This technique is most often used with Fourier transform ion cyclotron resonance mass spectrometers.
Surface induced dissociation
Isobaric tag for relative and absolute quantitation
An isobaric tag for relative and absolute quantitation (iTRAQ) is a reagent for tandem mass spectrometry that is used to determine the amount of proteins from different sources in a single experiment. It uses stable isotope labeled molecules that can be covalent bonded to the N-terminus and side chain amines of proteins. The iTRAQ reagents are used to label peptides from different samples that are pooled and analyzed by liquid chromatography and tandem mass spectrometry. The fragmentation of the attached tag generates a low molecular mass reporter ion that can be used to relatively quantify the peptides and the proteins from which they originated.
Tandem mass tag
A tandem mass tag (TMT) is an isobaric mass tag chemical label used for protein quantification and identification. The tags contain four regions: mass reporter, cleavable linker, mass normalization, and protein reactive group.
Tandem mass spectrometry can be used for protein sequencing. When intact proteins are introduced to a mass analyzer, this is called "top-down proteomics" and when proteins are digested into smaller peptides and subsequently introduced into the mass spectrometer, this is called "bottom-up proteomics" proteomics. Shotgun proteomics is a variant of bottom up proteomics in which proteins in a mixture are digested prior to separation and tandem mass spectrometry.
Tandem mass spectrometry can produce a peptide sequence tag that can be used to identify a peptide in a protein database. A notation has been developed for indicating peptide fragments that arise from a tandem mass spectrum. Peptide fragment ions are indicated by a, b, or c if the charge is retained on the N-terminus and by x, y or z if the charge is maintained on the C-terminus. The subscript indicates the number of amino acid residues in the fragment. Superscripts are sometimes used to indicate neutral losses in addition to the backbone fragmentation, * for loss of ammonia and ° for loss of water. Although peptide backbone cleavage is the most useful for sequencing and peptide identification other fragment ions may be observed under high energy dissociation conditions. These include the side chain loss ions d, v, w and immonium ions and additional sequence-specific fragment ions associated with particular amino acid residues.
Oligosaccharides may be sequenced using tandem mass spectrometry in a similar manner to peptide sequencing. Fragmentation generally occurs on either side of the glycosidic bond (b, c, y and z ions) but also under more energetic conditions through the sugar ring structure in a cross-ring cleavage (x ions). Again trailing subscripts are used to indicate position of the cleavage along the chain. For cross ring cleavage ions the nature of the cross ring cleavage is indicated by preceding superscripts.
Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases. The development of tandem mass spectrometry screening in the early 1990s led to a large expansion of potentially detectable congenital metabolic diseases that affect blood levels of organic acids.
- Accelerator mass spectrometry
- Charge remote fragmentation
- Cross section (physics)
- Mass-analyzed ion kinetic energy spectrometry
- Unimolecular ion decomposition
- IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "tandem mass spectrometer".
- IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "precursor ion".
- IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "parent ion".
- IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "product ion".
- IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "daughter ion".
- Bursey, Maurice M. (1991). "Comment to readers: Style and the lack of it". Mass Spectrometry Reviews 10: 1. doi:10.1002/mas.1280100102.
- Adams, J. (1992). "To the editor". Journal of the American Society for Mass Spectrometry 3 (4): 473. doi:10.1016/1044-0305(92)87078-D.
- Louris, John N.; Wright, Larry G.; Cooks, R. Graham.; Schoen, Alan E. (1985). "New scan modes accessed with a hybrid mass spectrometer". Analytical Chemistry 57 (14): 2918. doi:10.1021/ac00291a039.
- deHoffman, Edmond; Stroobant, Vincent (2003). Mass Spectrometry: Principles and Applications. Toronto: Wiley. p. 133. ISBN 0-471-48566-7.
- IUPAC gold book definition of metastable ion (in mass spectrometry) 
- IUPAC gold book definition of transient (chemical) species
- JAMS Vol. 7, Feb. 1996, pp 150-156
- Wells JM, McLuckey SA (2005). "Collision-induced dissociation (CID) of peptides and proteins". Meth. Enzymol. 402: 148–85. doi:10.1016/S0076-6879(05)02005-7. PMID 16401509.
- Sleno L, Volmer DA (2004). "Ion activation methods for tandem mass spectrometry". Journal of mass spectrometry : JMS 39 (10): 1091–112. doi:10.1002/jms.703. PMID 15481084.
- Olsen JV, Macek B, Lange O, Makarov A, Horning S, Mann M (September 2007). "Higher-energy C-trap dissociation for peptide modification analysis". Nat. Methods 4 (9): 709–12. doi:10.1038/nmeth1060. PMID 17721543.
- Cooper HJ, Håkansson K, Marshall AG (2005). "The role of electron capture dissociation in biomolecular analysis". Mass spectrometry reviews 24 (2): 201–22. doi:10.1002/mas.20014. PMID 15389856.
- Syka JE, Coon JJ, Schroeder MJ, Shabanowitz J, Hunt DF (2004). "Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry". Proc. Natl. Acad. Sci. U.S.A. 101 (26): 9528–33. Bibcode:2004PNAS..101.9528S. doi:10.1073/pnas.0402700101. PMC 470779. PMID 15210983.
- Mikesh LM, Ueberheide B, Chi A, Coon JJ, Syka JE, Shabanowitz J, Hunt DF (2006). "The utility of ETD mass spectrometry in proteomic analysis". Biochim. Biophys. Acta 1764 (12): 1811–22. doi:10.1016/j.bbapap.2006.10.003. PMC 1853258. PMID 17118725.
- US patent 7534622, Donald F. Hunt, Joshua J. Coon, John E.P. Syka, Jarrod A. Marto, "Electron transfer dissociation for biopolymer sequence mass spectrometric analysis", issued 2009-05-19
- McLuckey SA, Stephenson JL (1998). "Ion/ion chemistry of high-mass multiply charged ions". Mass spectrometry reviews 17 (6): 369–407. doi:10.1002/(SICI)1098-2787(1998)17:6<369::AID-MAS1>3.0.CO;2-J. PMID 10360331.
- Chi A, Huttenhower C, Geer LY, Coon JJ, Syka JE, Bai DL et al. (2007). "Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry.". Proc Natl Acad Sci U S A 104 (7): 2193–8. Bibcode:2007PNAS..104.2193C. doi:10.1073/pnas.0607084104. PMC 1892997. PMID 17287358.
- Frese, Christian K.; A. F. Maarten Altelaar; Henk van den Toorn; Dirk Nolting; Jens Griep-Raming; Albert J. R. Heck; Shabaz Mohammed (November 20, 2012). "Toward full peptide sequence coverage by dual fragmentation combining electron-transfer and higher-energy collision dissociation tandem mass spectrometry". Anal Chem. 84 (22): 9668–73. doi:10.1021/ac3025366. PMID 23106539.
- Syka, John EP; Coon JJ; Schroeder MJ; Shabanowitz J; Hunt DF (2004). "Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry". PNAS 101 (26): 9528–9533. doi:10.1073/pnas.0402700101. PMC 470779. PMID 15210983.
- Olsen JV; Macek B; Lange O; Makarov A; Horning S; Mann M (September 2007). "Higher-energy C-trap dissociation for peptide modification analysis.". Nature methods 4 (9): 709–712. doi:10.1038/nmeth1060. PMID 17721543.
- Frese, Christian K.; Houjiang Zhou; Thomas Taus; A. F. Maarten Altelaar; Karl Mechtler; Albert J. R. Heck; Shabaz Mohammed (March 1, 2013). "Unambiguous Phosphosite Localization using Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)". J Proteome Res. 12 (3): 1520–5. doi:10.1021/pr301130k. PMC 3588588. PMID 23347405.
- Coon JJ, Shabanowitz J, Hunt DF, Syka JE (June 2005). "Electron transfer dissociation of peptide anions". J. Am. Soc. Mass Spectrom. 16 (6): 880–2. doi:10.1016/j.jasms.2005.01.015. PMID 15907703.
- Budnik BA, Haselmann KF, Zubarev RA (2001). "Electron detachment dissociation of peptide di-anions: an electron–hole recombination phenomenon". Chemical Physics Letters 342 (3-4): 299–302. Bibcode:2001CPL...342..299B. doi:10.1016/S0009-2614(01)00501-2.
- Morgan JW, Hettick JM, Russell DH (2005). "Peptide sequencing by MALDI 193-nm photodissociation TOF MS". Meth. Enzymol. 402: 186–209. doi:10.1016/S0076-6879(05)02006-9. PMID 16401510.
- Little DP, Speir JP, Senko MW, O'Connor PB, McLafferty FW (1994). "Infrared multiphoton dissociation of large multiply charged ions for biomolecule sequencing". Anal. Chem. 66 (18): 2809–15. doi:10.1021/ac00090a004. PMID 7526742.
- Schnier PD, Price WD, Jockusch RA, Williams ER (1996). "Blackbody Infrared Radiative Dissociation of Bradykinin and Its Analogues: Energetics, Dynamics, and Evidence for Salt-Bridge Structures in the Gas Phase". Journal of the American Chemical Society 118 (30): 7178–7189. doi:10.1021/ja9609157. PMC 1393282. PMID 16525512.
- Dunbar RC (2004). "BIRD (blackbody infrared radiative dissociation): evolution, principles, and applications". Mass spectrometry reviews 23 (2): 127–58. doi:10.1002/mas.10074. PMID 14732935.
- Grill, Verena; Shen, Jianwei; Evans, Chris; Cooks, R. Graham (2001). "Collisions of ions with surfaces at chemically relevant energies: Instrumentation and phenomena". Review of Scientific Instruments 72 (8): 3149. Bibcode:2001RScI...72.3149G. doi:10.1063/1.1382641.
- Mabud, M. (1985). "Surface-induced dissociation of molecular ions". International Journal of Mass Spectrometry and Ion Processes 67 (3): 285. doi:10.1016/0168-1176(85)83024-X.
- Ong SE, Mann M (2005). "Mass spectrometry-based proteomics turns quantitative". Nature Chemical Biology 1 (5): 252–262. doi:10.1038/nchembio736. PMID 16408053.
- Bantscheff M, Schirle M, Sweetman G, Rick J, Kuster B (October 2007). "Quantitative mass spectrometry in proteomics: a critical review". Anal Bioanal Chem 389 (4): 1017–31. doi:10.1007/s00216-007-1486-6. PMID 17668192.
- Nikolov M, Schmidt C, Urlaub H (2012). "Quantitative Mass Spectrometry-Based Proteomics: An Overview". Methods in Molecular Biology 893: 85–100. doi:10.1007/978-1-61779-885-6_7. PMID 22665296.
- Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S, Khainovski N, Pillai S, Dey S, Daniels S, Purkayastha S, Juhasz P, Martin S, Bartlet-Jones M, He F, Jacobson A, Pappin DJ (2004). "Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents". Mol. Cell. Proteomics 3 (12): 1154–69. doi:10.1074/mcp.M400129-MCP200. PMID 15385600.
- Zieske LR (2006). "A perspective on the use of iTRAQ reagent technology for protein complex and profiling studies". J. Exp. Bot. 57 (7): 1501–8. doi:10.1093/jxb/erj168. PMID 16574745.
- Gafken PR, Lampe PD (2006). "Methodologies for characterizing phosphoproteins by mass spectrometry". Cell Commun. Adhes. 13 (5–6): 249–62. doi:10.1080/15419060601077917. PMC 2185548. PMID 17162667.
- Thompson A, Schäfer J, Kuhn K et al. (2003). "Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS". Anal. Chem. 75 (8): 1895–904. doi:10.1021/ac0262560. PMID 12713048.
- Angel, Thomas E.; Aryal, Uma K.; Hengel, Shawna M.; Baker, Erin S.; Kelly, Ryan T.; Robinson, Errol W.; Smith, Richard D. (2012). "Mass spectrometry-based proteomics: existing capabilities and future directions". Chemical Society Reviews 41 (10): 3912. doi:10.1039/c2cs15331a. ISSN 0306-0012.
- Hardouin J (2007). "Protein sequence information by matrix-assisted laser desorption/ionization in-source decay mass spectrometry". Mass spectrometry reviews 26 (5): 672–82. doi:10.1002/mas.20142. PMID 17492750.
- Shadforth I, Crowther D, Bessant C (2005). "Protein and peptide identification algorithms using MS for use in high-throughput, automated pipelines". Proteomics 5 (16): 4082–95. doi:10.1002/pmic.200402091. PMID 16196103.
- Mørtz E, O'Connor PB, Roepstorff P, Kelleher NL, Wood TD, McLafferty FW, Mann M (1996). "Sequence tag identification of intact proteins by matching tanden mass spectral data against sequence data bases". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8264–7. Bibcode:1996PNAS...93.8264M. doi:10.1073/pnas.93.16.8264. PMC 38658. PMID 8710858.
- Roepstorff P, Fohlman J (1984). "Proposal for a common nomenclature for sequence ions in mass spectra of peptides". Biomed. Mass Spectrom. 11 (11): 601. doi:10.1002/bms.1200111109. PMID 6525415.
- Richard S. Johnson, Stephen A. Martin and Klaus Biemann, Collision-induced fragmentation of (M + H)+ ions of peptides. Side chain specific sequence ions, International Journal of Mass Spectrometry and Ion Processes, Volume 86, 29 December 1988, Pages 137-154. 
- A. M. Falick, W. M. Hines, K. F. Medzihradszky, M. A. Baldwin and B. W. Gibson, Low-mass ions produced from peptides by high-energy collision-induced dissociation in tandem mass spectrometry, Journal of the American Society for Mass Spectrometry, Volume 4, Issue 11, November 1993, Pages 882-893. 
- Kevin M. Downard and Klaus Biemann, Amino acid sequence prerequisites for the formation of cn ion, Journal of the American Society for Mass Spectrometry Volume 4, Issue 11, November 1993, Pages 874–881. 
- Kevin M. Downard and Klaus Biemann, Methionine specific sequence ions formed by the dissociation of protonated peptides at high collision energies, Journal of Mass Spectrometry, Volume 30, Issue 1, January 1995, pages 25–32. 
- Zaia, Joseph (2004). "Mass spectrometry of oligosaccharides". Mass Spectrometry Reviews 23 (3): 161–227. doi:10.1002/mas.10073. ISSN 0277-7037.
- Bruno Domon, Catherine E Costello (1988). "A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates". Glycoconj. J. 5 (4): 397–409. doi:10.1007/BF01049915.
- Spina E, Cozzolino R, Ryan E, Garozzo D (2000). "Sequencing of oligosaccharides by collision-induced dissociation matrix-assisted laser desorption/ionization mass spectrometry". Journal of mass spectrometry : JMS 35 (8): 1042–8. doi:10.1002/1096-9888(200008)35:8<1042::AID-JMS33>3.0.CO;2-Y. PMID 10973004.
- Banoub, Joseph H.; Newton, Russell P.; Esmans, Eddy; Ewing, David F.; Mackenzie, Grahame (2005). "Recent Developments in Mass Spectrometry for the Characterization of Nucleosides, Nucleotides, Oligonucleotides, and Nucleic Acids". Chemical Reviews 105 (5): 1869–1916. doi:10.1021/cr030040w. ISSN 0009-2665.
- Thomas, Benjamin; Akoulitchev, Alexandre V. (2006). "Mass spectrometry of RNA". Trends in Biochemical Sciences 31 (3): 173–181. doi:10.1016/j.tibs.2006.01.004. ISSN 0968-0004.
- J. Wu; S. A. McLuckey (2004). "Gas-phase fragmentation of oligonucleotide ions". International Journal of Mass Spectrometry 237 (2–3): 197. Bibcode:2004IJMSp.237..197W. doi:10.1016/j.ijms.2004.06.014.
- Tarini BA (2007). "The current revolution in newborn screening: new technology, old controversies". Archives of pediatrics & adolescent medicine 161 (8): 767–72. doi:10.1001/archpedi.161.8.767. PMID 17679658.
- Kayton A (2007). "Newborn screening: a literature review". Neonatal network : NN 26 (2): 85–95. doi:10.1891/0730-08220.127.116.11. PMID 17402600.
- Chace DH, Kalas TA, Naylor EW (2003). "Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns". Clin. Chem. 49 (11): 1797–817. doi:10.1373/clinchem.2003.022178. PMID 14578311.
- McLuckey, Scott A.; Busch, Kenneth L.; Glish, Gary L. (1988). Mass spectrometry/mass spectrometry: techniques and applications of tandem mass spectrometry. New York, N.Y: VCH Publishers. ISBN 0-89573-275-0.
- McLuckey, Scott A.; Glish, Gary L. Mass Spectrometry/Mass Spectrometry: Techniques and Applications of Tandem. Chichester: John Wiley & Sons. ISBN 0-471-18699-6.
- McLafferty, Fred W. (1983). Tandem mass spectrometry. New York: Wiley. ISBN 0-471-86597-4.
- Sherman, Nicholas E.; Kinter, Michael (2000). Protein sequencing and identification using tandem mass spectrometry. New York: John Wiley. ISBN 0-471-32249-0.