Comparison of collision‐ versus electron‐induced dissociation of sodium chloride cluster cations

The collision‐induced dissociation (CID) and electron‐induced dissociation (EID) spectra of the [(NaCl)_m(Na)_n]ⁿ⁺ clusters of sodium chloride have been examined in a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer. For singly charged cluster ions (n = 1), mass spectra for CID and EID of the precursor exhibit clear differences, which become more pronounced for the larger cluster ions. Whereas CID yields fewer product ions, EID produces all possible [(NaCl)_xNa]⁺ product ions. In the case of doubly charged cluster ions, EID again leads to a larger variety of product ions. In addition, doubly charged product ions have been observed due to loss of neutral NaCl unit(s). For example, EID of [(NaCl)₁₁(Na)₂]²⁺ leads to formation of [(NaCl)₁₀(Na)₂]²⁺, which appears to be the smallest doubly charged cluster of sodium chloride observed experimentally to date. The most abundant product ions in EID spectra are predominantly magic number cluster ions. Finally, [(NaCl)_m(Na)₂]^{+ .} radical cations, formed via capture of low‐energy electrons, fragment via the loss of [(NaCl)_n(Na)] ^. radical neutrals. Copyright © 2008 John Wiley & Sons, Ltd.     

Diastereochemical differentiation of bicyclic diols using metal complexation and collision‐induced dissociation mass spectrometry

Metal complex formation was investigated for di‐exo‐, di‐endo‐ and trans‐2,3‐ and 2,5‐disubstituted trinorbornanediols, and di‐exo‐ and di‐endo‐ 2,3‐disubstituted camphanediols using different divalent transition metals (Co²⁺, Ni²⁺, Cu²⁺) and electrospray ionization quadrupole ion trap mass spectrometry. Many metal‐coordinated complex ions were formed for cobalt and nickel: [2M+Met]²⁺, [3M+Met]²⁺, [M–H+Met]⁺, [2M–H+Met]⁺, [M+MetX]⁺, [2M+MetX]⁺ and [3M–H+Co]⁺, where M is the diol, Met is the metal used and X is the counter ion (acetate, chloride, nitrate). Copper showed the weakest formation of metal complexes with di‐exo‐2,3‐disubstituted trinorbornanediol yielding only the minor singly charged ions [M–H+Cu]⁺, [2M–H+Cu]⁺ and [2M+CuX]⁺. No clear differences were noted for cobalt complex formation, especially for cis‐2,3‐disubstituted isomers. However, 2,5‐disubstituted trinorbornanediols showed moderate diastereomeric differentiation because of the unidentate nature of the sterically more hindered exo‐isomer. trans‐Isomers gave rise to abundant [3M–H+Co]⁺ ion products, which may be considered a characteristic ion for bicyclo[221]heptane trans‐2,3‐ and trans‐2,5‐diols. To differentiate cis‐2,3‐isomers, the collision‐induced dissociation (CID) products for [3M+Co]²⁺, [M+CoOAc]⁺, [2M–H+Co]⁺ and [2M+CoOAc]⁺ cobalt complexes were investigated. The results of the CID of the monomeric and dimeric metal adduct complexes [M+CoOAc]⁺ and [2M–H+Co]⁺ were stereochemically controlled and could be used for stereochemical differentiation of the compounds investigated. In addition, the structures and relative energies of some complex ions were studied using hybrid density functional theory calculations. Copyright © 2009 John Wiley & Sons, Ltd.     

Differentiation of lisinopril and its RSS diastereomer by liquid chromatography combined with collision‐induced dissociation mass spectrometry

A simple and sensitive liquid chromatography tandem multiple‐stage mass spectrometry (HPLC/MS/MS) method suitable for bulk lisinopril analysis was developed, by which lisinopril and its RSS isomer were separated and differentiated. In the collision‐induced dissociation (CID) mass spectra of the [M + H]⁺ ions, the abundance of the fragment ion of m/z 246 for lisinopril was about two times higher than the ion of m/z 245; however, the former fragment ion was noted to be a little lower than the latter for RSS isomer at all collision energies. In the CID mass spectra of the [M + Li]⁺ ion, the abundance of the rearrangement ion of m/z 315 for the RSS isomer was about three times higher than that for lisinopril. Furthermore, the difference was supported by the results of energy‐resolved mass spectrometry (ERMS) in the test range of collision energies. Similar differences were also observed between the CID mass spectra of lisinopril and RSS isomer methylester, which indicated that the RSS isomer could be rapidly characterized by the CID mass spectra of both the protonated and lithium adduct ion. Elemental compositions of all the ions were confirmed by Fourier Transform ion cyclotron resonance ESI mass spectrometry (FT‐ICR‐ESI/MS). In addition, theoretical computations were carried out to support the experimental results. Copyright © 2009 John Wiley & Sons, Ltd.     

Molecular formula analysis of fragment ions by isotope‐selective collision‐induced dissociation tandem mass spectrometry of pharmacologically active compounds

The purpose of this work is to explore the mass fragment characterization of commonly used drugs through a novel approach, which involves isotope‐selective tandem mass spectrometry (MS/MS). Collision‐induced dissociation (CID) was performed with a low‐resolution linear ion trap mass spectrometer in positive electrospray ionization. Three pharmacologically active ingredients, i.e. omeprazole, meloxicam and brinzolamide, selected as model compounds in their own formulation, were investigated as a sodiated adduct [C₁₇H₁₉N₃O₃S + Na]⁺ (omeprazole) and as protonated adducts, [C₁₄H₁₃N₃O₄S₂ + H]⁺ and [C₁₂H₂₁N₃O₅S₃ + H]⁺, meloxicam and brinzolamide, respectively. Selecting a narrow window of ±0.5 m/z units, precursor ion fragmentation by CID‐MS/MS of isotopologues A + 0, A + 1 and A + 2 was found very useful to confirm the chemical formula of product ions, thus aiding the establishment of characteristic fragmentation pathways of all three examined compounds. The correctness of putative molecular formula of product ions was easily demonstrated by exploiting the isotope peak abundance ratios (i.e. I_F+0/I_F+1 and I_F+0/I_F+2) as simple constraints in low‐resolution MS instrumentations. Copyright © 2014 John Wiley & Sons, Ltd.     

Structural determination of sildenafil and its analogues in dietary supplements by fast‐atom bombardment collision‐induced dissociation tandem mass spectrometry

Sildenafil and its analogues, which are used as illegal additives in several dietary supplements, were isolated by liquid‐liquid extraction and column chromatography and analyzed by fast‐atom bombardment mass spectrometry (FAB‐MS). Structures of sildenafil and its derivatives were elucidated by FAB‐tandem mass spectrometry (MS/MS) with exact mass measurement in the positive‐ion mode. To find structurally diagnostic ions for the sildenafil analogues, authentic sildenafil was preferentially analyzed by high‐energy collision‐induced dissociation (CID)‐MS/MS. The CID‐MS/MS spectra of [M+H]⁺ precursor ions resulted in the formation of numerous characteristic ions via a series of dissociative processes. The product ions formed by CID provided important information on the modification of the piperazine ring, the phenylsulfonyl group and the pyrazolopyrimidine moiety of sildenafil. By interpreting their MS/MS spectra, the chemical structures of sildenafil analogues isolated from dietary supplements could be elucidated and fragmentation patterns were proposed. To clearly identify the sidenafil derivatives in dietary supplements, some of the derivatives such as acetildenafil, homosildenafil and hydroxyhomosildenafil which are not commercially available were synthesized and compared with their MS/MS spectra. In addition, high‐resolution mass measurements were conducted to obtain the elemental compositions of sildenafil and its analogues. Copyright © 2009 John Wiley & Sons, Ltd.     

Fatty acid neutral losses observed in tandem mass spectrometry with collision‐induced dissociation allows regiochemical assignment of sulfoquinovosyl‐diacylglycerols

A full characterization of sulfoquinovosyldiacylglycerols (SQDGs) in the lipid extract of spinach leaves has been achieved using liquid chromatography/electrospray ionization‐linear quadrupole ion trap mass spectrometry (MS). Low‐energy collision‐induced dissociation tandem MS (MS/MS) of the deprotonated species [M ? H]^? was exploited for a detailed study of sulfolipid fragmentation. Losses of neutral fatty acids from the acyl side chains (i.e. [M ? H ? RCOOH]^?) were found to prevail over ketene losses ([M ? H ? R'CHCO]^?) or carboxylates of long‐chain fatty acids ([RCOO]^?), as expected for gas‐phase acidity of SQDG ions. A new concerted mechanism for RCOOH elimination, based on a charge‐remote fragmentation, is proposed. The preferential loss of a fatty acids molecule from the sn‐1 position (i.e. [M ? H ? R₁COOH]^?) of the glycerol backbone, most likely due to kinetic control of the gas‐phase fragmentation process, was exploited for the regiochemical assignment of the investigated sulfolipids. As a result, 24 SQDGs were detected and identified in the lipid extract of spinach leaves, their number and variety being unprecedented in the field of plant sulfolipids. Moreover, the prevailing presence of a palmitic acyl chain (16:0) on the glycerol sn‐2 position of spinach SQDGs suggests a prokaryotic or chloroplastic path as the main route for their biosynthesis. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparison of in‐source collision‐induced dissociation and beam‐type collision‐induced dissociation of emerging synthetic drugs using a high‐resolution quadrupole time‐of‐flight mass spectrometer

In‐source collision‐induced dissociation (CID) is commonly used with single‐stage high‐resolution mass spectrometers to gather both a molecular formula and structural information through the collisional activation of analytes with residual background gas in the source region of the mass spectrometer. However, unlike tandem mass spectrometry, in‐source CID does not involve an isolation step prior to collisional activation leading to a product ion spectrum composed of fragment ions from any analyte present during the activation event. This work provides the first comparison of in‐source CID and beam‐type CID spectra of emerging synthetic drugs on the same instrument to understand the fragmentation differences between the two techniques and to contribute to the scientific foundations of in‐source CID. Electrospray ionization–quadrupole time‐of‐flight (ESI‐Q‐TOF) mass spectrometry was used to generate product ion spectra from in‐source CID and beam‐type CID for a series of well‐characterized fentanyl analogs and synthetic cathinones. A comparison between the fragmentation patterns and relative ion abundances for each technique was performed over a range of fragmentor offset voltages for in‐source CID and a range of collision energies for beam‐type CID. The results indicate that large fragmentor potentials for in‐source CID tend to favor higher energy fragmentation pathways that result in both kinetically favored pathways and consecutive neutral losses, both of which produce more abundant lower mass product ions relative to beam‐type CID. Although conditions can be found in which in‐source CID and beam‐type CID provide similar overall spectra, the in‐source CID spectra tend to contain elevated noise and additional chemical background peaks relative to beam‐type CID.     

Increasing specificity of tandem mass spectrometry by laser‐induced dissociation

Mass spectrometry offers an arsenal of tools for diverse proteomic investigations. This perspective article reviews some of the recent developments in the field of coupling laser‐induced dissociation with mass spectrometry (LID‐MS). Strategies involving labelling with a chromophore to induce specific photo‐absorption properties are considered, with a focus on specific amino acid derivatization. Some of the opportunities and challenges of LID‐MS after targeted labelling for increasing specificity in complex sample analysis are discussed.