Product ion transition

The software tools accompanying the QTRAP MS/MS allow set-up of multiple selected reaction monitoring (SRM) transitions for all likely metabolites after the major product ion transitions for the dosed compound are known. Because QTRAP MS/MS can monitor up to 100 SRM transitions during a single assay, the SRM transitions required for quantitation of the dosed compound and internal standard are obtained along with the possible metabolite transitions. During sample analysis, when a possible metabolite transition exceeds a preset threshold value, the QTRAP MS/MS performs an enhanced product ion (EPI) scan. When the assay is complete, the EPI scans can be used to determine whether the hits are metabolites, and if they are metabolites, what part of the molecule has changed. Thus, one analytical run provides both quantitative and metabolite information. 

Liquid chromatography-mass spectrometry (LC-MS) or liquid chromatography-tandem-mass spectrometry (LC-MS/MS) has been in general the technique of choice for the analysis of PFCs. Therein detailed information about the main experimental conditions used for analysis, such as LC-MS/MS precursor-product ion transitions, were reported. 

For the detection, a tandem mass spectrometer Quattro Micro API ESCI (Waters Corp., Milford, MA) with a triple quadrupole was employed. The instrument was operated in electrospray in the positive ionization mode (ESI+) with the following optimized parameters capillary voltage, 0.5 kV source block temperature, 130 °C nebulization and desolvation gas (nitrogen) heated at 400 °C and delivered at 800 L/h, and as cone gas at 50 L/h collision cell pressure, 3 x 1(F6 bar (argon). Data was recorded in the multiple reaction monitoring (MRM) mode by selection of the two most intense precursor-to-product ion transitions for each analyte, except for the ISs, for which only one transition was monitored. The most intense transition for each analyte was used for quantitative purposes. Table 2 shows MRM transitions, cone voltages and collision energies used for the analysis of the antidepressants included in the LC-MS/MS method. 

In addition, due to lack of MS/MS capability, SIM has been more commonly performed on single quadrupole MS, while SRM has been broadly adapted on triple quadrupole (Figure 13-4) and ion-trap mass spectrometers. The increase in sensitivity and selectivity of SRM stem from the ion-chromatogram (i.e., LC-MS/MS) obtained by specific precursor-to-product ion transition for an analyte of interest (Figure 13-4). Conversely, in an SIM mode, the relative background noise due to the presence of other isobaric species (i.e., ions with a same m/z as the analyte of interest) can result in a lower signal-to-noise ratio for the analyte. Due to the widespread acceptance of SRM in quantitative analysis, the remaining part of this section focuses on a description of tandem-mass spectrometry (MS/MS), which is utilized in SRM (or MRM) experiments. 

TABLE 2. MS-MS precursor/product-ion transitions for the compounds analyzed. 

Since PFCs generally present many transitions, the most intense can be used for quantitative analysis (quantifier transition) and the second one (qualifier transition) to confirm the identification. Taking into account the performance criteria of the EU Commission, the MRM ratio between the abundances of the two selected precursor and product ion transitions (qualifier transition to quantifier transition) was used by many authors to confirm analyte identification [11,17,31]. However, it has been reported that the use of only two transitions could result in false-positive or falsenegative results when an interfering matrix compound coelutes with the analyte of interest [57-59], The alternative would be to monitor more than two transitions, but this is not always possible, since it depends on the analyte and on the generation of stable and characteristic MS-MS spectra [59],... 

Acquiring tandem MS data for a specific parent ion across the tissue section can provide more specific images because a specific parent ion/product ion transition can be mapped. The image thus generated would be a tandem MS image. As has been shown previously (6), performing tandem MS on a ion trap provides the... 

Retention times and MRMs (precursor/product ion transitions) for the internal standards, anabolic agents and metabolites, beta-blockers, (32-agonists, and glucocorticoids are shown in Tables 2 and 3. Depending on the compound, 1-3 product ions are monitored in MRM mode for the screening procedure. 

Generally, in LC-MS analysis, a particular pair or pairs of precursor-/product-ion transitions are monitored at a specified elution time. Of course, these transitions at such an elution time should be predetermined utilizing authentic compounds or close analogs. Alternatively, a data-dependent acquisition approach could be set up with a certain type of instruments [60]. In either case, some degree of preknowledge about the individual lipid species present in the samples is required since currently available instruments are still unable to perform an infinite number of transitions at an elusion time due to the limitation of instmmental duty cycle and/or sensitivity. Moreover, similar to the SIM method, the linear dynamic range, limit of detection, and calibration curves of the species of interest should generally be predetermined for quantitative analysis of lipid species. Thus, the constmcted ion peak area of each species can be compared to a standard curve of the species under identical experimental conditions. 

Fig. 7-2. Potential energy E as a function of the reaction coordinate for reactions of the P-nitrogen of arenediazonium ions with nucleophiles yielding (Z)- and (is)-azo compounds, a) Reactant-like transition states (e. g., reaction with OH) b) product-like transition states (e. g., diazo coupling reaction with phenoxide ions product = cyclohexadienone-type o-complex (see Sec. 12.8).

In the case of aldicarb, oxamyl, and 3-hydroxycatbofuran, the ion transitions go from [M + NH4]+ —> product ions. 

For APCI (if matrix effects become a problem in ESI), the mobile phase consisted of (A) 9 1 methanol-water containing 50 mM ammonium acetate and (B) water containing 50 mM ammonium acetate-methanol (9 1). The gradient was held at 50% A-50% B for 10 min and was then changed to 90% A-10% B in 22 min (held for 3 min). The HPLC column was a Zorbax RX-C8, 4.6-mm i.d. x 250 mm, 5 pm particle size, with a flow rate of l.OmLmin and a 50-pL injection. Table 8 shows the ion transitions (parent to product ions) that were monitored for HPLC/ESI-MS/MS. For single-stage HPLC/ESI-MS, Table 9 shows the ions that were monitored. 

Figure 1 SRM chromatograms of (a) fenamiphos and metabolites and (b) imidacloprid and metabolites. IS refers to the stable labeled isotopes. The values below the names refer to the mass transitions, i.e., M -b 1 -> product ion for the metabolite...

Exothermic Reactions of Transition Metal Ions with Hydrocarbons. Cross sections for the formation of product ions resulting from the interaction of Ni+ with n-butane are shown in Figure 6 for a range of relative kinetic energies between 0.2 and 4 eV. In contrast to the results shown in Figure 3, several products (reactions 6-8) are formed with large cross section at low energies. These cross sections decrease with... 

Chovan et al.30 described a system that integrates different components of bioanalysis including automatic in vitro incubation, automatic method development (mainly SRM transitions for LC/MS/ MS analysis), and a generic LC method for sample analysis to minimize human intervention and streamline information flow. Automaton software (Applied Biosystems) was used for automatic MS method development. Flow injection was used instead of a HPLC column to decrease run time to 0.8 min per injection. Two injections were performed. The first was performed to locate the precursor ion and optimal declustering potential (DP). The second injection was performed to locate the product ion and optimal collision energy (CE). 

The Cr+ and Mn+ ions have ground-state electronic configurations 3<754.v° and 3d54s1, respectively, and both react slowly (relative to other transition metal ions) with S8 but do not react with P4 (whereas other transition metal ions react readily). The Ca+ (3d°4s1) ion reacts rapidly with S8 (98) (more rapidly than most bare transition metal ions) but reacts very slowly with P4 producing the [CaP]+ ion. The Ba+ ion also reacts readily with S8 but is unreactive to P4 (99). These observations indicate that the electronic configuration of the metal ion and the properties of the reacting molecule are important in determining reactivity. The formation of stable product ions is also important. Whereas most transition metals react with S8 to produce [MS4]+ ions, the product ion for Ca+ and Ba+ is the [MS3]+ ion. 

The Ti+ ions, produced by using a laser vaporization source (cooled by collisions with He) have been reacted with NH3 to produce the dehydrogenated product ions, [TiNH]+ (100). Many early transition metal ions and Os+ produce the [MNH]+ ion (9,106). The ion [TiNH]+ was reactive toward NH3 and increasing the concentration of NH3 in the drift tube (100) allowed up to four NH3 molecules to add to the [TiNH]+ ion, thus producing five-coordinate Ti in the gas phase. 

The reactions of some transition metal cluster ions have been described in a review by Parent and Anderson (201). The review covered reactions reported up to 1992 and so the reactions reported here are generally later than 1992. A recent review by Knickelbein (202) discusses the reactions of cation clusters of iron, cobalt, nickel, copper, silver, niobium, and tungsten with small molecules such as H2 and D2. Some of the reactions in Knickelbein s review are included in the following tables of reactions (Tables IV and V). Table IV gives examples of the reactions of transition metal cluster ions and includes the vaporization source, experimental apparatus, the reactants, and the observed product ions. A few examples from these tables will be selected for further discussion. 

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