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Photodegradation study of 3,5-diamino-6-chloro- N-(2-(methylamino)ethyl)pyrazine-2-carboxamide using preparative SFC and LC-MS
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2016 (English)Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

In this project the photodegradation of 3,5-diamino-6-chloro-N-(2-(methylamino)ethyl)pyrazine-2-carboxamide was studied. A hypothetical degradation pattern for the compound was proposed and the aim of the project was to study the formed secondary photodegradants and to, if possible, structure elucidate some of these compounds. In order to do this, the parent compound was photodegraded in two steps, where a primary photodegradant was isolated using semi-preparative supercritical fluid chromatography (SFC) and then further degraded into the secondary photodegradants.

The photodegradation was first carried out in aqueous solution, where the parent compound was irradiated in UV-A light of 300-400 nm. This resulted in a primary photodegradant with a molecular ion of m/z = 227, where the chloride in position 6 of the pyrazine group had been replaced by a hydroxyl group. During the large scale photodegradation, prior to the preparative purification, the yield of primary photodegradant was very low due to the photodegradation being dependent on both sample volume and concentration and due to the primary photodegradant also being unstable in aqueous solution at room temperature.

Due to the above mentioned difficulties the parent compound was photodegraded in methanol instead of water in order to avoid the freeze-drying process where a lot of the primary photodegradant was lost. This resulted in a primary photodegradant with a molecular ion of m/z = 241, where the chloride had been replaced by a methoxy group instead of a hydroxyl group. This compound was more stable which allowed workup by rotary evaporation, instead of freeze-drying, before the preparative purification. This primary photodegradant was isolated using semi-preparative SFC on a Viridis® BEH Prep OBD TM column (250 x 30 mm, 5 µm) and a Luna HILIC column (250 x 30 mm, 5 µm) with MeOH/NH3 100/1 v/v as organic modifier. About 1.2 mg material was isolated and further photodegradation tests in ordinary water and 18O-water were conducted.

Some secondary photodegradants were observed in LC-MS analyses, and their element compositions were proposed by accurate mass results. Fundamental structures for these compounds were proposed. Further structural investigational analyses are needed for confirmation in the future.

Place, publisher, year, edition, pages
2016. , 62 p.
UPTEC K, ISSN 1650-8297 ; 16005
Keyword [en]
photodegradation, UPLC, SFC, liquid chromatography, supercritical fluid chromatography, mass spectrometry, freeze drying, 18O-water, analytical chemistry, structure elucidation, photodegradants
National Category
Medical Laboratory and Measurements Technologies Analytical Chemistry
URN: urn:nbn:se:uu:diva-301500OAI: oai:DiVA.org:uu-301500DiVA: diva2:957864
External cooperation
Educational program
Master Programme in Chemical Engineering
2016-06-13, BMC B1:128b, Husargatan 3, 75123, Uppsala, 11:00 (Swedish)
Available from: 2016-09-06 Created: 2016-08-23 Last updated: 2016-09-06Bibliographically approved

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