In the pharmaceutical industry, a higher attrition rate during the drug discovery process means a lower drug failure rate in the later stages. This translates into shorter drug development time and reduced cost for bringing a drug to market. Over the past few years, analytical strategies based on liquid chromatography/mass spectrometry (LC/MS) have gone through revolutionary changes and presently accommodate most of the needs of the pharmaceutical industry. Among these LC/MS techniques, collision induced dissociation (CID) or tandem mass spectrometry (MS/MS and MS(n)) techniques have been widely used to identify unknown compounds and characterize metabolites. MS/MS methods are generally ineffective for distinguishing isomeric compounds such as metabolites involving oxygenation of carbon or nitrogen atoms. Most recently, atmospheric pressure ionization (API) source decomposition methods have been shown to aid in the mass spectral distinction of isomeric oxygenated (N-oxide vs hydroxyl) products/metabolites. In previous studies, experiments were conducted using mass spectrometers equipped with a heated capillary interface between the mass analyzer and the ionization source. In the present study, we investigated the impact of the length of a heated capillary or heated ion transfer tube (a newer version of the heated capillary designed for accommodating orthogonal API source design) in inducing for-API source deoxygenation that allows the distinction of N-oxide from hydroxyl compounds. 8-Hydroxyquinoline (HO-Q), quinoline-N-oxide (Q-NO) and 8-hydroxyquinoline-N-oxide (HO-Q-NO) were used as model compounds on three different mass spectrometers (LCQ Deca, LCQ Advantage and TSQ Quantum). Irrespective of heated capillary or ion transfer tube length, N-oxides from this class of compounds underwent predominantly deoxygenation decomposition under atmospheric pressure chemical ionization conditions and the abundance of the diagnostic [M + H - O](+) ions increased with increasing vaporizer temperature. Furthermore, the results suggest that in API source decompostion methods described in this paper can be conducted using mass spectrometers with non-heated capillary or ion transfer tube API interfaces. Because N-oxides can undergo in-source decomposition and interfere with quantitation experiments, particular attention should be paid when developing API based bioanalytical methods.

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This paper presents a comprehensive collision-induced dissociation and ab initio study of small boron oxide cations, B n O m +, motivated by a need for more accurate and reliable structural and thermodynamic information on both neutral and ionic boron oxides. Absolute fragmentation cross sections were measured for all observable B n O m + (n < 4, m < 5) parent ions at center-of-mass collision energies ranging from 0.08 to 10 eV. Quantitative dissociation thresholds, generated from the experimental data by correcting for the collision energy spread resulting from the beam energy distribution and the thermal motion of the target gas, are compared to ab initio dissociation energies determined from Gaussian-2 calculations.

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Reactions of B n O m + and B n O m H+ clusters (n ≤ 3, m ≤ 4) with D2O have been studied over a collision energy range from 0.1 to 10 eV (center of mass). The reactivity and product branching are found to be highly dependent on the structure of the reactant ion. When available, the preferred site of attack is on a terminal B atom, and the chemistry is dominated by O and OD addition. Even for the most reactive clusters the peak reaction efficiency is only 5−7%, indicating the presence of a bottleneck to reaction. When the reactant has no terminal B atoms, reaction is 1 order of magnitude less efficient and appears to be dominated by attack at nonterminal B atoms. The B n O m H+ react similarly, suggesting that the added H atom does not block the reactive sites. This is in contrast to the isoelectronic reaction with HF, where H addition decreased reactivity dramatically. The results are compared with those for related reactions, and with recent ab initio results. In general, theory is consistent with experiment; however, there remain a few problem species.

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