TiO{sub 2} Photocatalyzed Oxidation of Drugs Studied by Laser Ablation Electrospray Ionization Mass Spectrometry

Journal Article · Fri Apr 19 04:00:00 EDT 2019 · Journal of the American Society for Mass Spectrometry

DOI:https://doi.org/10.1007/S13361-018-2120-X· OSTI ID:22923042

Franssen, Maurice C. R. ^[1]; Miikkulainen, Ville; Ritala, Mikko ^[2]; Zuilhof, Han ^[1]; Kostiainen, Risto ^[3]; Nielen, Michel W. F., ^[1]

---

1. Wageningen University, Laboratory of Organic Chemistry (Netherlands)
2. University of Helsinki, Department of Chemistry (Finland)
3. University of Helsinki, Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy (Finland)

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 TiO{sub 2} 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) TiO{sub 2}-photocatalysis laser ablation electrospray ionization (LAESI) MS method for the analysis of drug candidates. This method was proven to be compatible with both TiO{sub 2}-coated glass slides as well as solutions containing suspended TiO{sub 2} 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. .

• OSTI ID: 22923042
• Journal Information: Journal of the American Society for Mass Spectrometry, Journal Name: Journal of the American Society for Mass Spectrometry Journal Issue: 4 Vol. 30; ISSN 1044-0305; ISSN JAMSEF
• Country of Publication: United States
• Language: English

Related Subjects

77 NANOSCIENCE AND NANOTECHNOLOGY
ABLATION
CHROMATOGRAPHY
GLASS
IONIZATION
LASER RADIATION
MASS SPECTROSCOPY
NANOPARTICLES
PHOTOCATALYSIS
TESTOSTERONE
TIME RESOLUTION
TITANIUM OXIDES