Bogdan Kralj

The use of quadrupole-time-of-flight mass spectrometer for the elucidation of diclofenac biotransformation products in wastewater

The work presented herein discusses the potential of liquid chromatography-quadrupole-time-of-flight mass spectrometry (QqToF-MS) for the chemical structure elucidation of pharmaceutical degradation products (DPs). The model compound, the nonsteroidal anti-inflammatory drug diclofenac was subjected to microbiological transformation in a laboratory scale pilot wastewater treatment plant (WWTP) and its transformation products were detected in the outlet samples. Their chemical structures were elucidated using the principal features of the instrument, i.e. high resolution, accurate mass and MS/MS capability. A hydroxy-diclofenac, a benzoquinone imine derivative and a nitro analogue of diclofenac were successfully identified. The final structural elucidation of the fourth transformation product was not successful. Overall, the study emphasises the capabilities and potential of quadrupole-time-of-flight mass spectrometer showing it to be a powerful tool in both structure elucidation and confirming the identity of environmental contaminants.

Application of complementary mass spectrometric techniques to the identification of ketoprofen phototransformation products.

Ketoprofen (KP) is a nonsteroidal anti-inflammatory drug, which during UV irradiation rapidly transforms into benzophenone derivatives. Such transformation products may occur after topical application of KP, which is then exposed to sunlight resulting in a photo-allergic reaction. These reactions are mediated by the benzophenone moiety independently of the amount of allergen. The same reactions will also occur during wastewater or drinking water treatment albeit their effect in the aqueous environment is yet to be ascertained. In addition, only a few such transformation products have been recognised. To enable the detection and structural elucidation of the widest range of KP transformation products, this study applies complementary chromatographic and mass spectrometric techniques including gas chromatography coupled to single quadrupole or ion trap mass spectrometry and liquid chromatography hyphenated with quadrupole-time-of-flight mass spectrometry. Based on structural information gained in tandem and multiple MS experiments, and on highly accurate molecular mass measurements, chemical structures of 22 transformation products are proposed and used to construct an overall breakdown pathway. Among the identified transformation products all but two compounds retained the benzophenone moiety--a result, which raises important issues concerning the possible toxic synergistic effects of KP and its transformation products. These findings trigger further research into water treatment technologies that would limit their entrance into environmental or drinking waters.

An investigation into the reactivity of ions arising from different regions of a translational, energy release distribution: a need for angular collimation

Abstract A new method which enables ion from various portions of a metastable peak to be isolated for study is presented. Reactions have been found in which ions, m 2 + formed as products of fragmentation of metastable ions, m 1 + , will themselves undergo unimolecular fragmentation to form ions m 3 + . By selecting ions m 2 2 from various parts of the metastable peak for the reaction step m 1 + → m 2 + , their reactivity can be studied as a function of their position within the metastable peak. Such studies have enabled ions m 2 + containing different amounts of internal energy to be identified. The work has also demonstrated that the ability to obtain accurate translational energy release distributions from the shapes of metastable peaks is dependent upon good angular collimation of the reactant ions.

Mass spectrometric investigations of α‐ and β‐cyclodextrin complexes with ortho‐, meta‐ and para‐coumaric acids by negative mode electrospray ionization

The mass spectrometric characterization of aqueous solutions of alpha- and beta-cyclodextrins (CDs) and o-, m- and p-coumaric acids (CAs) by negative ion electrospray ionization (ESI) indicates that the [CD+CA](-) ions were sourced from the inclusion complex present in solution and from the anion attached to CD molecules formed in the spray processes. The anion adducts formed in the spray process contribute significantly to the signal intensity of an ionized inclusion complex thus overestimating the calculated stability constant (K) of solution-phase complexes by one to two orders of magnitude. The relative intensities of anion adducts in mass spectra depend on the concentration ratio of the anion and the CD in spray droplets, while the relative intensity of the ionized inclusion complex depends on CD and CA concentrations in solutions and the value of K. Ion Mobility Spectrometry Mass Spectrometry [IMS-MS] measurements show that the collision cross-section (Omega) values of the [CD+CA](-) or [(CD)(2+)CA](2-) and [CD+CA](2) (2-) complex ions are 5-6% larger than or equal to CD(-) or [CD](2) (2-), respectively. Therefore, in the gas phase the anion adducts [CD+CA(-)] on cyclodextrin molecules possess the same conformations as the ionized inclusion complexes [CD+CA](-).

Fast atom bombardment of molecules in the gaseous state

Abstract Involatile molecules usually exhibit a protonated molecular ion MH + in positive and an (M- H) − species in negative ion fast atom bombardment mass spectra. If a compound evaporates it may be ionized by fast atom impact in the gaseous state. Fast atom bombardment mass spectra of some volatile compounds are compared to those obtained by electron impact ionization.

Modification of a mattauch—herzog mass spectrometer for ion kinetic energy measurements

Abstract Two major modifications have been made to a type CEC 21-110 C Mattauch—Herzog double focussing mass spectrometer. In the first of these, provision has been made for independent scanning of the electric sector and ion kinetic energy (IKE) spectra can be plotted at high sensitivity on a channeltron multiplier placed between the sectors. In the second modification an extra electric sector has been fitted, following the magnetic sector, so that mass-analyzed ion kinetic energy (MIKE) spectra can also be obtained. Examples of the performance achieved in both the modes of operation are given.

Application of tandem mass spectrometry to the analysis of chlorinated compounds

The application of high-resolution gas chromatography–mass spectrometry and tandem mass spectrometry (MS–MS) in environmental analysis is demonstrated with three typical compound types, i.e., polychlorinated biphenyls (PCBs), polychlorinated alkanes (PCAs) and polychlorinated naphthalenes (PCNs), found in/or during the preparation of some environmental samples from a contaminated area. With ‘multiple reaction monitoring’ of some selected reaction products from a collision cell (i.e., loss of one or two chlorine radicals from a molecular ion) by the Q-analyser of a VG-AutospecQ mass spectrometer, unambiguous qualitative and quantitative data for various isomeric PCBs and PCNs could be obtained. By using this approach, time consuming and extremely demanding sample preparation could be reduced or avoided. In addition, the determination of trace amounts of higher chlorinated PCBs in paraffin oil illustrates the unique capability of MS–MS.

How a modification (8-aza-3-deaza-2'-deoxyguanosine) influences the quadruplex structure of Hotoda's 6-mer TGGGAG with 5'- and 3'-end modifications.

We have synthesized a modified 6‐mer using Hotodas 6‐mer TGGGAG with 5′‐ and 3′‐end modifications as a template. We have replaced from one to all four 2′‐deoxyguanosines by 8‐aza‐3‐deaza‐2′‐deoxyguanosine (c3z8dG, 1) in order to investigate the anti‐HIV structure activity relationship (SAR). ODN 4 (TGGG*AG) is the only one that exhibits a moderate anti‐HIV‐1 activity. †In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.

METASTABLE AND COLLISION-ACTIVATED DECOMPOSITION OF PROTONATED MOLECULES OF ISOMERIC N7- AND N9-SUBSTITUTED PURINES IN THE GAS PHASE

The structures and reactivities of protonated metastable and collision-activated molecules of isomeric N7- and N9-substituted purines were investigated using fast atom/ion bombardment ionization and mass analysed ion kinetic energy spectrometry methods. Calculated proton affinities (PAs) of isomeric purine derivatives and the intensities of the observed metastable-ion peaks revealed a direct correlation of PA with the reactivity of protonated molecules. The reactivity of the N9-substituted purines possessing N3-site specific proton affinities, i.e. N3–H+, relates to the strength of hydrogen bonding of N3–H+ to oxygen atoms(s) of the N9-substituent, e.g. CH2—O—CH2CH2—O—C(CH3) = O or CH2—OCH2CH2—O—H. Various intramolecular (‘intra-ion’) hydrogen-bond(s) in the protonated molecules of isomeric purine derivates were revealed using proton affinities and metastable-ion peak intensities.

A study of doubly charged ions in aluminum and iron acetylacetonates

Abstract Aluminum and iron acetylacetonates give a series of doubly charged ions in their electron impact mass spectra, some of which exhibit unusually large abundances. Of particular interest is the (M-30)2+ ion in Al(acac)3, which is the most abundant doubly charged ion in its spectrum, while no presence of its singly charged counterpart could be detected. The formation of doubly charged ions was discussed on the basis of the odd—even electron rule and the tendency of iron to change its valency state. Charge separation reactions have been studied for all doubly charged ions in an attempt to gain some insight into their structures. For two reactions of the (M-30)2+ ion in Al(acac)3 an intercharge distance of ∼ 20 A was obtained, which is by far the largest value reported so far.