Multiple-reaction monitoring experiments

Various analyzers have been used to analyze phenolic compounds. The choice of the MS analyzer is influenced by the main objective of the study. The triple quadrupole (QqQ) has been used to quantify, applying multiple reaction monitoring experiments, whereas the ion trap has been used for both identification and structure elucidation of phenolic compounds. Moreover, time-of-flight (TOF) and Fourier-transform ion cyclotron resonance (FT-ICR) are mainly recommended for studies focused on obtaining accurate mass measurements with errors below 5 ppm and sub-ppm errors, respectively (Werner and others 2008). Nowadays, hybrid equipment also exists, including different ionization sources with different analyzers, for instance electrospray or atmospheric pressure chemical ionization with triple quadrupole and time-of-flight (Waridel and others 2001). 

D. B. Martin, T. Holzman, D. May, A. Peterson, A. Eastham, J. Eng, and M. McIntosh, MRMer, an interactive open source and cross-platform system for data extraction and visualization of multiple reaction monitoring experiments, Mol. Cell. Proteomics, 1 (2008) 2270-2278. 

The method for chloroacetanilide soil metabolites in water determines concentrations of ethanesulfonic acid (ESA) and oxanilic acid (OXA) metabolites of alachlor, acetochlor, and metolachlor in surface water and groundwater samples by direct aqueous injection LC/MS/MS. After injection, compounds are separated by reversed-phase HPLC and introduced into the mass spectrometer with a TurboIonSpray atmospheric pressure ionization (API) interface. Using direct aqueous injection without prior SPE and/or concentration minimizes losses and greatly simplifies the analytical procedure. Standard addition experiments can be used to check for matrix effects. With multiple-reaction monitoring in the negative electrospray ionization mode, LC/MS/MS provides superior specificity and sensitivity compared with conventional liquid chromatography/mass spectrometry (LC/MS) or liquid chromatography/ultraviolet detection (LC/UV), and the need for a confirmatory method is eliminated. In summary,... 

Figure 13-18. Structure of STI571, CGP 74588, and the internal standard. Arrows indicate that the product-ion that was selected for the multiple-reaction monitoring (MRM) experiment [59,60]. For complete metabolic profile and disposition of STI571 (rmatinib, Gleevec ) in humans, see reference 103.

Traditionally, quantitative analysis of drugs and their metabolites both in vivo and in vitro is mainly dependent on multiple reaction monitoring (MRM) with triple quadruple instruments. In contrast, drug metabolite detection and identification often involve various types of mass spectrometers (Ma and Chowdhury, 2007 Prakash et al., 2007). Full-scan MS experiments followed by data-dependent tandem MS/MS acquisition with ion trap or linear ion trap mass spectrometers are carried out to identify common metabolites whose... 

Table 19.1 Ions monitored for determination of niacin by isotope dilution mass spectrometry using positive electrospray ionization. Both natural and labelled nicotinic acid are protonated in positive ion electrospray ionization, giving quasi-molecular ions at mass-to-charge ratios (m/z) of 124 and 128, respectively, which can be monitored directly in selected ion recording (SIR) experiments and selected as the parent ions in multiple reaction monitoring (MRM) experiments. In MRM experiments protonated nicotinic acid can be induced to produce daughter ions at several other m/z values, but the given transitions are the ones with the highest signal intensity.

To improve the specificity while retaining the high sensitivity, a new method (i.e., selected or multiple reaction monitoring (SRM/MRM, Chapter 2)) is evolved from the SIM technique, which is only focused on one miz of a compound to the SRM that is focused on both a molecular (or precursor) ion and a fragment-ion resultant from the precursor ion. The specific experiment in known as a "transition" and is usually written as precursor-ion mass fragment-ion mass. The only requirement to perform this technique is that the mass spectrometer employed has to possess the capability to perform MS/MS. 

Multiple reaction monitoring, MS/MS scan to monitor selected product ions only, essentially the same experiment as selected reaction monitoring, SRM. 

Note SRM is preferably performed on triple quadrupole, quadrupole ion trap, and Q-TOF hybrid instruments due to their ease of setting up the experiment and to their speed of switching between channels if monitoring of multiple reactions plays a role. 

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