Tandem mass spectrometry principles

Confirmation of suspected residue findings relies on the various chromatographic principles of cleanup and determination (GPC, NP-LC, GC), and is further supported by re-analysis of the final extract(s) on a GC stationary phase of different polarity, providing modified selectivity, or by the use of GC with specific mass spectrometric detection [GC/MS or gas chromatography/tandem mass spectrometry (GC/MS/MS)]. 

Principles and Characteristics Analytical multistage mass spectrometry (MSn) relies on the ability to activate and dissociate ions generated in the ion source in order to identify or obtain structural information about an unknown compound and to analyse mixtures by exploiting two or more mass-separating steps. A basic instrument for the currently most used form, tandem mass spectrometry (MS/MS), consists of a combination of two mass analysers with a reaction region between them. While a variety of instrument set-ups can be used in MS/MS, there is a single basic concept involved the measurement of the m/z of ions before and after a reaction in the mass spectrometer the reaction involves a change in mass and can be represented as ... 

The hallucinogenic principles of magic mushrooms psilocin and psilocybin were selectively detected and quantified in mushrooms samples using HPLC ODS separation coupled with tandem mass spectrometry, reaching detection limits in the picogram range [25]. 

Figure 22-21 Principle of selected reaction monitoring, also called tandem mass spectrometry, mass spectrometry/mass spectrometry, or MS/MS.

Specificity. The potentially very high analytical specificity of tandem mass spectrometry as HPLC detector results from using the molecular mass of the analyte and its specific disintegration behaviour as detection principle. 

To benefit general readers, the discussion has been limited to methodologies that are accessible to nonspecialists and that can be carried out on commercially available spectrometers without special modifications. The chapter illustrates the principles of mass spectrometry by demonstrating how various techniques [MALDI, ESI, Fourier transform ion cyclotron resonance (FT-ICR), ion traps, and tandem mass spectrometry (MS-MS)] work. It also provides examples of utilizing mass spectrometry to solve biological and biochemical problems in the field of protein analysis, protein folding, and noncovalent interactions of protein-DNA complexes. 

Background. As an analytical technique, tandem mass spectrometry is just entering its second decade of development. The variety of reported applications belies its relative youth. Tandem mass spectrometry (MS/MS) grew out of early work which used metastable ion transitions in order to establish ion structures and interrelationships. After extensive applications to ion structural studies, its usefulness in direct catplex mixture analysis became apparent with the early work of Cooks (1-3). Its successes in problem solving are summarized in a recent book edited by McLafferty (4). New, with several ccnmercial instruments available, MS/MS is being evaluated for application in several new areas, including biochemical analysis, forensic chemistry, and food and flavor analyses. The principles of MS/MS will be surmarized in the first part of this chapter. The second part of the chapter will deal with the reported applications of MS/MS to flavor analysis. 

Quadrupole ion trap mass analyzers merge the trapping characteristics of the ICR with the physical principles of the linear quadrupole mass analyzer. Quadrupole ion traps produce time-dependent spectra with excellent sensitivity and tandem mass spectrometry capabilities, but unlike the ICR they provide these ion trapping characteristics with physically smaller and considerably less expensive instrumentation, giving them a reputation as a powerful and accessible tool for both qualitative and quantitative mass spectrometry [43-47]. The capability of quadrupole ion traps to be configured with either internal and external ionization sources has expanded their utility for modem analytical applications [48—52]. 

Michael Kinterand Nicholas E. Sherman Protein Sequencing and Identification Using Tandem Mass Spectrometry Chhabil Dass Principles and Practice of Biological Mass Spectrometry Mike S. Lee LC/MSApplications in Drug Development... 

Figure 4.1. Basic principle of tandem mass spectrometry. (Reproduced from C. Dass, Principles and Practice of Biological Mass Spectrometry, Wiley-Interscience, 2001.)...

In principle however, this method should be portable to other mass spectrometer systems capable of chemical ionization and tandem mass spectrometry. An [M+54] ion was reported using atmospheric pressure chemical ionization (APCI) with a predominantly acetonitrile solvent while analyzing extremely long-chain polyunsaturated fatty acids (16). Such an observation is promising for the use of this method for the analysis of low- or nonvolatile lipids, such as triglycerides and phospholipids. 

This section deals with some general principles of tandem mass spectrometry and its applicability to quantitative analysis. The MS/MS acronym is used in this book as a general term for aU tandem mass spectrometry techniques. More detailed descriptions of how the principles are exploited in practice for the various instrumental types are given in later sections of this chapter. The general concept of tandem mass spectrometry in qualitative (structural) analysis is that additional chemical information, over and above that contained in a conventional onedimensional mass spectrum, can be obtained by examining the connectivity relationships among some or all of the ions in that mass spectrum. The connectivities arise as a result of the dissociation reactions that lead to the fragment ions in a mass spectrum, e.g. ... 

Another ambient method, called AP-DIOS-MS, was also used for the identification of amphetamines and fentanyls in forensic samples. The principle is similar to that of DIOS, but occurs at atmospheric pressure. The use of tandem mass spectrometry (MS/MS) allowed unambiguous identification of the amphetamines and fentanyls (Pihlainen et al. 2005). AP-DIOS-MS/MS was also successfully applied to the identification of authentic compounds from drug seizures. Common diluents and tablet materials did not disturb the analysis and compounds were unequivocally identified. The limits of detection (LODs) for amphetamines and fentanyls with AP-DIOS-MS/ MS were 1-3 pmol, indicating excellent sensitivity of the method (Pihlainen et al. 2005). Protein digest analysis (250 finol of bovine serum albumin) by AP-DIOS-MS was also performed... 

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