Abstract
Budesonide is a corticosteroid used for the treatment of asthma via various matrices and inhalation mechanisms. An unknown peak of Budesonide aqueous formulation has been investigated during stability study wherein the impurity level observed around 0.1% well below the threshold 0.5%. The approach to identify anonymous species was adopted as first to generate the impurity in sample, isolate, enrich and was subjected to LC-MS/MS and NMR for spectral studies. Based on the spectral data the anonymous species were identified as a “Lumibudesonide’’ ((5aR,5bS,5cS,6S,7aS,7bS,10aR,11aS,11bS)-6-hydroxy-7b-(2-hydroxyacetyl)-5b,7a-dimethyl-9-propyl 1,5a,5b,5c,6,7,7a,7b,10a,11,11a,11b dodecahydrocyclopenta[2'',3'']cyclopropa [1'',2'':3', 4']benzo [1',2':4,5]indeno [1,2-d][1,3]dioxol-5(2H)-one), which is observed in photolysis of Budesonide.
Highlights
Impurity profiling of pharmaceutical active ingredients is an essential part of the research and developmental cycle
The anonymous species at retention time ~48.3 (RRT 1.9) (Figure 1(a)) was observed in Budesonide drug product ~0.1% well below the threshold of 0.5%
The impurity was observed ~4% after photo-irradiation in presence of organic solvent such as Acetonitrile/Methanol when analysed by a compendial method. It was clear from the LC-MS/MS spectral observation the RRT about 1.9 peak is an rearranged isomer of Budesonide
Summary
Impurity profiling of pharmaceutical active ingredients is an essential part of the research and developmental cycle. The very fact that a degradant can be generated from a stress study would verify the degradation mechanism, from which the structure of the unknown degradant may be inferred with high confidence level In such cases the NMR spectroscopy is used to confirm the structure deduced from the outcome of the LC-MS/MS analysis and forced degradation study. The Morrison established through a series of elegant papers [6] [7] [8] [9] that intramolecular energy transfer (both singlet-singlet and triplet-triplet) occurred from the phenyl “antenna” to C17 keto group by the way of throughbond mechanism This has led to a different photochemistry observed by the direct excitation of ketone chromophore. Since many steroidal drugs are commonly used and several reports on their phototoxic effects have been reported [12] [13] [14] [15], it was expected that such photochemical mechanisms might have relevance for the mechanism of phototoxicity
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