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

Vajjha, Soujanya; Bommuluri, Vijay; Rumalla, Chidananda Swamy; Doddipalla, Raju; Kaliyaperumal, Muralidharan; Korupolu, Raghu Babu

doi:10.1016/j.jpba.2019.04.010

Cited by 8 publications

(3 citation statements)

References 3 publications

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“…Several documented drug examples are there in literature including acetaminophen (which on hydrolysis yields p-aminophenol and acetic acid), 27 chloramphenicol. 28 Formation of this product has also been previously reported 24,25 and very recently, as a common degradation product generated under both acidic and basic hydrolytic conditions.…”

Section: Discussionsupporting

confidence: 63%

“…One degradation product ( I ) was formed under acid hydrolytic conditions and this has been previously reported as hydrolytic degradation product of ibrutinib. 24 Two degradation products I and II were formed under base hydrolytic conditions. Two products ( III and IV ) were generated under oxidative conditions.…”

Section: Resultsmentioning

confidence: 97%

“…22 As per ICH drug stability test guideline Q1A (R2), inherent stability characteristics of a drug should be studied under prescribed stress conditions. 23 Literature study revealed one recent study relating to the characterization of forced degradation products of this drug, 24 in which, two novel degradants were reported. Hence, the present study was designed to conduct a forced degradation study on ibrutinib under ICH-recommended conditions of hydrolytic, photolytic, oxidative and thermal stress and to attempt the identification of various degradation products generated, utilizing hyphenated LC-UV/PDA and LC-Q/TOF-MS techniques.…”

Section: Introductionmentioning

confidence: 99%

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Identification and characterization of stress degradation products of ibrutinib by LC-UV/PDA and LC-Q/TOF-MS studies

Mondal,

Bali,

Sharma

2023

Eur J Mass Spectrom (Chichester)

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The anticancer drug ibrutinib was subjected to stress degradation studies under the ICH-prescribed hydrolytic, photolytic, oxidative and thermal stress conditions, and its degradation behavior was studied. A significant degradation was noted for the drug under acidic/alkaline hydrolytic, acid/alkaline photolytic, and oxidative conditions. The UPLC-UV/PDA studies revealed the generation of six degradation products (I–VI), and these were adequately resolved from the drug under the developed chromatographic conditions over a Kinetex® C18 (100 mm×4.6 mm; 2.6 μm) column employing isocratic elution method. Detection wavelength was selected as 289 nm. The UPLC-UV/PDA method conditions were extrapolated to UPLC-MS/TOF studies. All the six degradation products were found to be ionized in the total ion chromatogram, and the products could be identified and characterized from their mass spectral data. The possible degradation route of ibrutinib leading to generation of various products was also postulated.

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