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'']
The present work encompasses identification and characterization of major degradation product (DP) of OSM observed in base hydrolytic stress study. The separation of DP was carried out on a non-polar stationary phase by using high-performance liquid chromatography system (HPLC). Using waters X-bridge (250 mm × 4.6 mm, 5 µm) C18 column with gradient elution program. For the characterization study, stress samples were subjected to HPLC and UPLC-QTOF-MS/MS and based on mass fragmentation pattern, plausible structure was deduced. Further, the DP was isolated using semi-preparative liquid chromatography and concentrated the fractions using lyophilization. The isolated DP was subjected to extensive 1D (1H, 13C, and DEPT-135) and 2D (COSY, HSQC and HMBC) nuclear magnetic resonance (NMR) studies to authenticate the structure. The impurity was unambiguously named as N-( 2-((2-(dimethylamino)ethyl)(methyl)amino)-4-metho-xy-5-((4-(1-methyl -1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-3-methoxypropanamide. Additionally, the In-Silico structure activity relation (QSAR) assessed through statistical based software's DEREK Nexus TM , and MultiCASE, Case Ultra TM widely accepted and respected software's for DP and OSM.
Arformoterol (R, R) is an enantiomer of racemic formoterol, was the first long-acting beta agonist (LABA), approved by U.S. food and Drug Administration (FDA). The Arformoterol which is used for the treatment of Chronic obstructive pulmonary disease (COPD) are inhaled bronchodilator drugs which are delivered directly to the patient's airways through a different mechanism. The formulated drug product is kept for stability study as per ICH guideline [1] and during its stability interval analysis by HPLC (High performance liquid chromatography), an unknown peak observed at level around 0.1% which is well below the identification threshold of 0.5% but after heating it crossed the identification threshold. The approach to identify anonymous species of Arformoterol aqueous formulation was adopted as first to generate the impurity in sample, isolate, enrich and Characterize through LC-MS/MS and NMR Spectroscopy. Based on the spectral data the anonymous species was identified as an "Imine impurity", it is secondary degradant of Amine impurity of Arformoterol formed due to reaction with leachable observed in LDPE respules.
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