Degradation studies of Ibrutinib under stress conditions: Characterisation and structural elucidation of novel degradants

• Published in: Journal of pharmaceutical and biomedical analysis 2019-08, Vol.172, p.9-17
• Main Authors: Vajjha, Soujanya, Bommuluri, Vijay, Mohan P, K.V.K., Rumalla, Chidananda Swamy, Doddipalla, Raju, Kaliyaperumal, Muralidharan, Korupolu, Raghu Babu
• Format: Article
• Language: English
• Subjects: Chromatography, High Pressure Liquid; Drug Stability; Drug Storage; HR-MS/MS; Ibrutinib; ICH guidelines; LCMS; NMR; Oxidation-Reduction; PREP-HPLC; Pyrazoles - chemistry; Pyrimidines - chemistry; Spectrometry, Mass, Electrospray Ionization
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2019.04.010

[Display omitted] •Ibrutinib was subjected to various stress conditions like acid, base, oxidative thermal and photolytic conditions.•Ibrutinib is labile to acid and basic conditions.•Two degradation products are formed in basic condition and one degradation product formed in acidic condition which is same as DP-1 in basic condition.•DP-1 & DP-2 were isolated by Preparative-HPLC and structurally characterised by expansive analysis of HRMS and NMR spectral studies. The aim of the research work is to study the degradation behaviour of Ibrutinib (IBN) which is performed under different stress conditions according to International Conference on Harmonization guidelines (ICH). The study included monitoring degradation of the Ibrutinib drug under acidic, base, oxidation, thermal and photolytic conditions followed by isolation and characterisation of degradation products (DP) by Liquid Chromatography Mass Spectrometry (LCMS), High resolution Mass Spectrometry (HR-MS/MS) and Nuclear Magnetic Resonance (NMR) studies. The IBN drug is stable under oxidation, thermal and photolytic conditions. The degradation of drug is observed under acidic and basic conditions. Two novel degradation products are formed which are not reported in the literature. The LCMS method has been developed for chromatographic separation of drug and its degradation products which were attained on C18 BEH UPLC column (50 mm X 2.1 mm, 1.7 μm). The combination of 0.05% Acetonitrile in water and 0.05% Formic acid in water are used as a mobile phase. The flow rate is 0.6 ml/min and UV wavelength monitored at 215 nm. Acetonitrile and water are used as diluents.