TiO2 Photocatalyzed Oxidation of Drugs Studied by Laser Ablation Electrospray Ionization Mass Spectrometry

Fred A M G Van Geenen,Michel W F Nielen,Han Zuilhof,Mikko Ritala,Risto Kostiainen,Maurice C R Franssen,Ville Miikkulainen

doi:10.1007/s13361-018-2120-x

Abstract

In drug discovery, it is important to identify phase I metabolic modifications as early as possible to screen for inactivation of drugs and/or activation of prodrugs. As the major class of reactions in phase I metabolism is oxidation reactions, oxidation of drugs with TiO2 photocatalysis can be used as a simple non-biological method to initially eliminate (pro)drug candidates with an undesired phase I oxidation metabolism. Analysis of reaction products is commonly achieved with mass spectrometry coupled to chromatography. However, sample throughput can be substantially increased by eliminating pretreatment steps and exploiting the potential of ambient ionization mass spectrometry (MS). Furthermore, online monitoring of reactions in a time-resolved way would identify sequential modification steps. Here, we introduce a novel (time-resolved) TiO2-photocatalysis laser ablation electrospray ionization (LAESI) MS method for the analysis of drug candidates. This method was proven to be compatible with both TiO2-coated glass slides as well as solutions containing suspended TiO2 nanoparticles, and the results were in excellent agreement with studies on biological oxidation of verapamil, buspirone, testosterone, andarine, and ostarine. Finally, a time-resolved LAESI MS setup was developed and initial results for verapamil showed excellent analytical stability for online photocatalyzed oxidation reactions within the set-up up to at least 1 h.Graphical

Highlights

M etabolism of drugs is an important aspect of their efficacy after administration to the body
laser ablation electrospray ionization (LAESI)-mass spectrometry (MS) was examined as a direct analysis tool in TiO2 photocatalysis; the generated oxidation products were critically compared with data of previously reported oxidation products of the model compounds verapamil, buspirone, and testosterone [7, 10, 11, 13, 20]
A first notable practical aspect was that LAESI, like desorption electrospray ionization (DESI), was able to analyze samples on surfaces without any sample pretreatment or lengthy chromatographic separation

Summary

Introduction

M etabolism of drugs is an important aspect of their efficacy after administration to the body. Apart from electrochemistry approaches [4, 5], titanium dioxide (TiO2) photocatalysis is a simple non-enzymatic method to generate oxidation reaction products similar to those obtained by phase I biochemical transformations [6,7,8,9,10,11,12,13]. LC-MS has been used as analytical method of choice for identification of the drug reaction products in most TiO2 photocatalyzed oxidation studies [6,7,8,9,10,11,12].

Results

Conclusion