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

Abstract

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.

Chromatographic, Polarographic and Ion-Selective Electrodes Methods for Chemical Analysis of Groundwater Samples in Hydrogeological Studies

“…The GC-MS, LC-DAD-MS and LC-MS/MS techniques are important techniques used for most of organic compounds and their metabolite or reaction products identification and quantification [21,22]. Due to their selectivity and sensitivity, they are particular important and powerful methods for metabolite or by-product identification of many reactions in the environment (such as biodegradation, photo-oxidation, chemical oxidation and others).…”

“…They may be used to estimate the polarity and volatility of the degradation products and can be compared, if available, with the standards. For a more accurate identification, degradation product spectral data have to be collected by use of dedicated detection instruments such as UV spectroscopy or mass spectrometry (MS) [22]. When standard compounds are available, LC-UV or GC-MS spectral data of the unknown degradation products are compared with those of standard compounds.…”

“…The mass spectrometry (MS) is considered a principal tool for identifying new products of oxidation of organic compounds, especially since it enables an efficient analysis of trace amounts of analytes in complex organic mixtures [22]. Such complicated environmental or biological samples require separation of components prior to mass spectrometric analysis, which justifies the use of hyphenated techniques such as GC-MS or LC-MS.…”

“…The single-stage quadrupole (Q) and an ion trap (IT) both hyphenated to a GC, and a quadrupole-time-offlight (QTOF) MS coupled to an LC can also be used. In the Q mass analyzer, the ions generated in the source undergo electron impact (EI) fragmentation, which results in complex, ambiguous spectral data and hence in non-selectivity that is its main disadvantage [22]. In contrast, the IT mass detector has the unique ability to isolate and to accumulate ions.…”

“…In contrast, the IT mass detector has the unique ability to isolate and to accumulate ions. By iterating ion trapping and scanning, it allows the generation of collision-induced dissociation (CID) spectra of the parent and fragment ions (and their fragment ions), thus increasing the level of confidence in assigning a particular structure [22]. Alternatively, the hybrid QTOF, in which the final resolving mass filter of a triple Q is replaced by a TOF analyzer, not only allows MS 2 operation but also has the necessary accuracy and resolution to give exact-mass measurements [22,28].…”