Suppression of the ionization

The pH value also affects the ionization of acidic and basic analytes and their electromigration. Since this migration can be opposite to that of the electroos-motic flow, it may both improve and impair the separation. This effect is particularly important in the separation of peptides and proteins that bear a number of ionizable functionalities. Hjerten and Ericson used monolithic columns with two different levels of sulfonic acid functionalities to control the proportion of EOF and electromigration. Under each specific set of conditions, the injection and detection points had to be adjusted to achieve and monitor the separation [117]. Another option consists of total suppression of the ionization. For example, an excellent separation of acidic drugs has been achieved in the ion-suppressed mode at a pH value of 1.5 [150]. 

Gradients of aqueous and organic mobile phases are typically used for LC-MS/MS analysis of drug compounds and metabolites. The most common aqueous solvents are water with 0.1 % formic acid or 0.1 % acetic acid (v/v) or volatile buffers like 5 mM ammonium-acetate or ammonium-formate. Often adjusted to a certain pH value with the corresponding acid or base (the pH of the eluents will have to be optimized with respect to the polarity of the analytes, since ionic species will have very low or no retention on the reversed pahse LC-columns). Other volatile buffers can be used as well. Phosphate buffers should be avoided, since they will cause suppression of the ionization and thus lead to very bad analytical performance (Venn 2000). Reagents like triethyl-amine should also be avoided as mobile phase or as part of mobile phases. They induce ion suppression as well. In terms of the organic solvents, methanol and acetonitrile are very widely used and they are very well suitable for LC-MS. Other solvents can be used as well, as long as they are compatible with the materials used in the LC-MS system. 

In a similar way as for the aromatic amino acids, the change of the rate-determining step is a consequence of the suppression of the ionization of the COOH group of HX+ which causes the concentration of X to become too small to maintain a decomposition rate faster than the rate of C deprotonation. 

Levothyroxine is another example of an active pharmaceutical ingredient with relatively poor stability that is available as a USP analytical reference standard in the free acid form, while the drug is formulated as the sodium salt in most commercial preparations.84 Levothyroxine is prone to extensive photochemical decomposition85 that is thought to be exacerbated by the facile ionization of the phenolic hydroxyl group.86 Supply of the USP analytical reference standard as the free acid provides a more stable form through suppression of the ionization of the phenolic hydroxyl. 

Szepesi et al. reported an ion-pair separation of eburnane alkaloids on a chemically bonded cyanopropyl stationary phase. As counter-ion, di-(2-ethyl hexyl)phosphoric acid or (+)-10-camphorsulfonic acid were used in a mobile phase consisting of hexane - chloroform -acetonitrile mixtures (Table 8.8, 8.9). Because of the poor solubility of the latter pairing ion, diethylamine (Table 8.9) was added to the mobile phase. Addition of diethylamine considerably reduced the k1 of the alkaloids, due to suppression of the ionization of the alkaloids. However, due to the strong acidic character of the pairing ion, ion-pairs were still formed under these conditions. The camphorsulfonic acid containing mobile phases were found to be very useful for the separation of optical isomers (Table 8.10, 8.11, Fig.8.8) 6. It was also found that the selectivity of the system could be altered by choosing different medium-polarity solvents (moderator solvents) as dioxane, chloroform or tetrahydrofuran. The polar component of the solvent system affected peak shape. Based on these observations, a method was developed to analyze the optical purity of vincamine and vinpocetine. For the ana-... 

At energies above the ionization threshold of the H2O molecules, a number of remarkable phenomena were observed as illustrated in the emission spectra shown in Fig. 7.12. Under gas phase conditions and excitation at 67.1 nm (18.5 eV) channels (2) and (3) are accessible and contribute the /5,7, S and e Balmer lines of H and a broad structureless emission from H2O+ (cf. Fig. 7.12a), respectively. In the gas phase at 57.5 nm (21.6eV) only channel (3) is excited as identified from the broad structureless emission from H2O+ (cf. Fig. 7.12c). As a great surprise, for both wavelengths the emission spectra in helium droplets showed exclusively the Balmer lines of H (cf. Figs. 7.12b and 7.12d) which was interpreted as a suppression of the ionization channel (3) in favor of the predissociation channel (2). In addition the 57.5 nm excitation was in resonance with the pure helium droplets resulting in a rich emission in the... 

The common-ion effect of a salt of a weak base is similar to the weak add-anion situation just described. The suppression of the ionization of NH3 by the common cation, NH4, is pictured in Figure 17-3 and represented as follows. 

Ionization changes can be efficiently corrected with the use of an isotopically labeled IS, which possesses identical ionization response and fragmentation pattem. Therefore, deuterated IS can be used to correct both the overall method variability (e.g., sample preparation, injection, electrophoretic process, etc.) as well as matrix effects since the amount of suppression from interferents is expected to be similar. However, the total concentration of analyte and IS should be below the saturation of the ionization process. Guidelines to obtain a reproducible CE—MS method were published by Ohnesorge et al. and took into account the use of an isotopically labeled IS. 

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has contributed remarkably to unravelling the termination and initiation steps of the styrene/CO copolymerisation catalysed by the highly active bis-chelated complex [Pd(bipy)2](Pp5)2 in TFE [40]. Chain-end group analysis of the material produced in the absence of BQ showed that the termination by P-H elimination is accompanied by three different initiators two palladium alkyls from Pd-H formed by reaction of the precursor with CO and water (a and b) and a palladium carboalkoxy species formed by reaction of the precursor with the fluorinated alcohol and CO (c) (Chart 7.4). The suppression of the chain-transfer by alcoholysis was proposed to be responsible for the enhanced stability of the palladium acyl intermediates and hence for the high molecular weight of the copolymers produced. 

The direct mode is employed with eluents with significantly lower equivalent conductance than the analyte ion. Increase in sensitivity is obtained as the degree of the ionization of the eluent decreases, that is, with more weakly dissociated eluents, and non suppressed conductivity methods have been extensively developed using benzoate, phthalate [246], oxalate [53] or other partially ionized species as mobile phases. A key factor in the success of this technique is the use of an ion exchanger of low-exchange capacity, which in turn permits the use of a very dilute eluent. 

The effect of progressive annelation in the helicene series is a suppression of the intensities of all it-bonds relative to the o-bond system. Furthermore, the n-bonds become more symmetrical and the vibrational structure is blurred out. This indicates a substantial geometry change upon ionization. 

In the classical case, when the field intensity exceeds a threshold value, the electron s motion becomes chaotic and strong excitation and ionization takes place. In the quantum case instead, interference effects may lead to the suppression of the classical chaotic diffusion, the so-called quantum dynamical localization, and in order to ionize the atom, a larger field intensity is required (see Fig. 1). 

Bluhme, H., Knudsen, H., Merrison, J.P. and Poulsen, M.R. (1998). Strong suppression of the positronium channel in double ionization of noble gases by positron impact. Phys. Rev. Lett. 81 73-76. 

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