Photostability testing using online reactor HPLC hyphenation and mass spectrometric compund identification illustrated by ketoprofen as model compund

Abstract:

Investigations on the photochemical stability of pharmaceutical substances are mandatory in drug devel-opment and licensing as photo-induced degradation of an active pharmaceutical ingredient (API) maynot only lead to decreased API concentrations but also to toxic or reactive products. Thus, the US Food andDrug Administration (FDA) and the International Council for Harmonisation of Technical Requirementsfor Pharmaceuticals for Human Use (ICH) issued Guidance for Industry Q1B “Photostability Testing ofNew Drug Substances and Products” for testing of pure but also packed drugs. However, photoproductsare also known to be generated in vivo under sunlight exposure of the skin and lead to considerableamounts of adverse drug effects.Herein we present an alternative system that may be used for photostability testing mimicking both sit-uations. It combines a tailored photoreactor with an exchangeable pen light source and a modified HPLCsystem with online-SPE. Identification of photoproducts may be performed using mass spectrometry. Thepotential of accurate mass spectrometry as a tool for identification of photoproducts was demonstratedas well. A comparison of the online photoreactor system and the traditional photochamber irradiationwas performed using ketoprofen for proof of concept. In both designs acetylbenzophenone and ethylben-zophenone were detected as main photoproducts. The new device allows for fast and easy photostabilitystudies that may help to reduce time consuming in vitro experiments and animal trials. Using state ofthe art instruments kinetic studies could also easily be performed with qualitative and quantitative per-spectives combined into one experimental design with only very low amounts of API needed. This maybe useful in early drug development, where only small amounts of API are available. Scale-up may alsobe easily realized for the generation of reference material for quantification and quality control (QC)processes as well as for toxicity



Reference:
ASSAF, Jaber; GOMES, Diego Zulkiewicz; WUEST, Bernhard; PARR, Maria Kristina. Photostability testing using online reactor HPLC hyphenation and mass spectrometric compund identification illustrated by ketoprofen as model compund. Journal of Pharmaceutical and Biomedical Analysis, v.145, p.414-422, 2017.


Access to the article in the newspaper site:
https://doi.org/10.1016/j.jpba.2017.07.006

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