CAD-MIKE

Rivera, J., Carxach, S., Ventura, F. et al. FAB-CAD-MIKES. Analysis of nonionic surfactant in raw sewage sludges, (ed J.F.F.Todd), Proceedings of the 10th International Mass Spectrometry Conference, Swansea September 9-13 1985, J.Wiley, Basingstoke, UK (1985). 

A number of methods have been described for determination of tetracycline (chlortetracycline, tetracycline, and oxytetracycline) residues in tissues of food-producing animals (53-62), fish (63), eggs (64), and honey (65,66). Most of these methods use reversed-phase HPLC for determination. However, one uses TLC with UV densitometry ( ) and one uses GLC ( ), and one uses a direct mass spectrometric method CAD MIKE spectrometry (collisionally activated decomposition mass-analyzed ion kinetic spectrometry) for oxytetracycline in milk and meat (62). Several use solid-phase extraction in the cleanup procedure using XAD-2 resin (56,58) or Cj g cartridges... 

TD-IT, Thermal desorption-ion trap CAD MIKE, collisionally activated decomposition mass-analyzed ion kinetic energy MID, multiple ion detection FID, flame ionization detector NPD, nitrogen/phosphorus detector SIM, selected ion monitoring El, electron impact TMS, trimethylsilane MTBSTFA, N-methyl-N-(tetr.-butyldimethylsilyl)trifluoroacetamide. 

The [ArS02] ions, produced by dissociative secondary electron capture from sulfonamides 103c and 103d, dissociated both by simple cleavage (equation 35a-d) and by rearrangement (equation 35e) processes, as shown by their CAD MIKE spectra83. 

The CAD MIKE spectra of [ArS02] ions deriving from methyl-deuteriated 127d and from unlabelled p-toluene-iV-butylsulfonamide (103d) displayed the same decomposition pattern and the expected mass shifts83, pointing to the same structure, or mixture of structures. 

The application of MS/MS offers the advantage of simplifying cleanup procedures. To this end, CAD MIKES was applied to the detection of sulfonamide drugs and decomposition spectra were reported from [M + H]+ ions produced under Cl (i-C4H10)119. Equation 45 summarizes the most significant pathways leading to fragment... 

The addition of NO, to CH2=CH2 has been studied in the gas phase by TF-ISR, MIKE and CAD mass spectrometry, complemented by ab initio calculations at the MP2/6-31+G level. The results are believed to provide a clear answer to the principal mechanistic question addressed, demonstrating that the reaction yields an O-nitroso product (presumably CH3CHONO+) rather than a C-product.51... 

MIKE/CAD spectra, in addition to their interest for structural determinations, are... 

Figure 27. Unimolecular decompositions (MIKE, B/E) and decompositions induced by collision gas (MIKE/CAD and B/E/CAD).

As an example, it is difficult to distinguish the structures of the protonated molecules MH produced from isomeric compounds with the elemental formula CgHioO (cyclohexanone, cyclohexane oxide and 1,4-cyclohexane ether) [152] on the basis of their respective unimolecular decomposition spectra. Indeed, only the loss of water was observed in the MIKE spectra of these products. Collision-induced decomposition spectra (MIKE/CAD), on the other hand, lead to an easy structural distinction (Fig. 28). 

Indeed, it is possible to obtain MIKE/CAD spectra of isobaric ions [154a,b]. For example, after elimination of 43 amu fragment, cyclohexanone leads within the... 

Figure 28. MIKE/CAD spectra of various protonated molecules of 1,4-cyclohexane ether (a), cyclohexanone (b) and cyclohexane oxide (c) produced under tC4,H9/CI [152].

The MIKE/CAD spectra of each ion are sufficiently different so that we may admit the separation of these ions, as shown by the non-existence of ions arising from the loss of 4,5 or 6 hydrogen atoms, as well as that of the m/z 39 ion in the MIKE/CAD spectrum of the isobaric ion CaHjO]". Inversely, the very low intensity of the m/z 41 peak in the MIKE/CAD spectrum of the C4H7] ion is proof of the good separation of these isobaric ions Fig. 29). 

The MIKE and MIKE/CAD) method is used on a ZAB 2F reversed geometry instrument, designed by VG Micromass Instruments. 

Figure 29. MIKE/CAD spectra of C3H3O and QH, isobaric ions [m/z 55) produced from cyclohexanone under El conditions [154a].

Figure 34. MIKE/CAD spectra showing positively and negatively charged products both arising from the [M-H] anion of p-chlorobenzoic acid [164].

This program contains all the possibilities of rapid and sensitive analysis of metastable spectra, regardless of the mode employed, with averages of MIKE (or MIKE/CAD) spectra. 

It is often necessary to separate ions produced in the cell (pure CAD spectrum) from those occurring outside the cell (by spontaneous decompositions or by collision resulting from gas leaks in the analyzer). The pure MIKE/CAD spectrum is shifted by applying a negative voltage on the cell. 

In these conditions, 50 pg can be detected with a precision of 20%. A complete MIKE/CAD spectrum can be recorded with about 500 pg of mixture. Here again, the results are comparable to HR/MS, but the measurements are rapid and more specific. 

Figure 38. Analysis by MIKE/CAD mode of ion m/z 259 (MH ) produced from an authentic sample of biotin methyl ester (in CI/NH4) (a) and from the unknown mixture (b).

In order to obtain more intense molecular peaks, Levsen and co-workers [197] chose the field ionization (FI) method, much softer than electron impact ionization, and utilized collision-induced decompositions rather than unimolecular decompositions. They were thus able to identify estrone (m/z 270) and progesterone (m/z 314) in an artificial mixture (Table 13). The FI/MIKE/CAD spectra of the molecular ions are... 

Analysis of steroid mixtures using MIKE/CAD spectra under FI conditions (FI/CAD spectra) [197]... 

The development of MIKE/CAD or B/E/CAD linked scan methods will undoubtedly result in greater possibilities than those offered by methods of detecting metastable ions, especially at the level of sensitivity. 

Maquestiau et al. [209] identified fractions in complex mixtures of free marine sterols with MIKE/CAD of molecular ions formed in El. The method was tested on six samples from corals and sponges. For example, the El conventional mass spectrum of the fraction isolated from Emicella stricta is especially complex high-mass peaks are located... 

As stated above, the analysis of certain of these peaks in MIKE/CAD spectra is very useful for determining the structure of molecules [209], especially for demonstrating the presence of unsaturations, of cyclopropenes on side chains, etc. (Table 18). 

In practice, the situation is not as simple as that, since MIKE/CAD spectra have a low resolution, leading to a few difficulties when isomers (or fragment) ions are present (or compounds with new structures) and when performing certain identifications. Nevertheless, the objective can be achieved, as shown by this review [209]. 

When MIKE/CAD is applied to the study of molecular ions produced by El, it is possible to detect them specifically and with a very low detection threshold. The limitations of this methodology are greatly reduced when Cl is used, since molecular ions (protonated or not) which form may be very abundant. 

Cooks and co-workers [210] identified each individual protonated molecule MH from various steroids contained in biological matrices by studying their MIKE/CAD spectra. Collisions are necessary in this ionization mode in order to increase the number of characteristic daughter ions. In certain cases, however, spontaneous decompositions are sufficiently numerous, especially in the first FFR. 

The study of MIKE/CAD spectra of protonated molecules of various compounds characterized by a A -3-keto system (such as testosterone, corticosterone, norgesterel, etc.) leads to the demonstration of peaks with non-negligible intensities at m/z 147, 135, 123, 109 and 97, with ratios that are very close. Certain fragment ions, including the [MH-CH3OH] ion, produced from hydroxycortisone (with the same A -3-keto sequence) also generate the same characteristic ions, and thus a certain amount of caution is required. 

Protonated molecules from steroids with a phenolic A ring may be characterized similarly by the presence of intense peaks at m/z 157, 135 and 107, as well as [MH-H20] in their MIKE/CAD spectra. 

Protonated isomeric molecules, such as testosterone and dehydroepiandrosterone, are characterized in the MIKE/CAD spectra by peak widths, but also by intensities, which vary as a function of collision gas pressure. 

Thus, there is no difficulty in determining the sequence of the AcN-Gly-Ala-Leu-OCH3 peptide. In a more thorough report of this work [218], the authors presented all the aspects offered by the use of MIKE/CAD spectra, including the study of a mixture of oligopeptides with sufficient sensitivity the decreased possibility... 

The major disadvantage of MIKE/CAD spectra, however, is related to the widening of metastable peaks, which reduces energy resolution. 

All three include the C4H9 radical and can decompose spontaneously (or collision-ally) to eliminate either the primary (-CH2-CH(CH3)2) or secondary (-CH(CH3)-CH2-CH3) isobutyl radical. Consequently, several differences are observed in the MIKE/CAD spectra. However, the greatest differences appear in the decomposition spectra of m/z 103 ion (Table 22), which is consistently present when the polypeptide has an He or Leu residue in terminal position. 

MIKE and MIKE/CAD spectra of ion (CD3NH =CH(C4H,))m/z 103 produced from peptides where the Leu (or lieu) group is present in various positions [218]... 

The importance of these NICI (negative ion chemical ionization) spectra of modified polypeptides led Howe and co-workers [222] to study the spectra of the free compounds. Thus, with OH as reagent ion with a mixture of three tripeptides, in addition to fragment ions, [M-H] molecular ions are produced in sufficient abundance (Fig. 77) to be analyzed by collisions (MIKE/CAD spectrum). 

For example, the deprotonated molecule [M-H] of the Pro-Leu-Gly-OH tripeptide (m/z 284) decomposes collisionally with argon and provides the MIKE/CAD spectrum shown in Figure 78. 

Figure 79. Main Aj and Zj ions observed in the MIKE/CAD spectrum of [M-H] " deprotonated peptide.

Now, the Fast Atom Bombardment (FAB) desorption technique associated with the MIKE/CAD technique is preferred, since a constant ion current is obtained. 

It is to be borne in mind that it is not always necessary to perform MIKE/CAD spectra, since occasionally spontaneous decompositions are sufficient. 

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