LC and LC–MS/MS studies for identification and characterization of new degradation products of ibrutinib and elucidation of their degradation pathway

Mehta, Lovekesh; Naved, Tanveer; Grover, Parul; Bhardwaj, Monika; Mukherjee, Debaraj

doi:10.1016/j.jpba.2020.113768

Cited by 27 publications

(7 citation statements)

References 8 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: Lc-q/tof-ms Characterization Of Stress Degradation Productssupporting

confidence: 64%

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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Section: Lc-q/tof-ms Characterization Of Stress Degradation Productssupporting

confidence: 64%

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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“…In literature, there are several LC-MS/MS and HPLC methods available for analysis of degradation products of anticancer drugs. [12][13][14] The present work was designed to study in vitro metabolism of anticancer drug, belinostat using rat liver microsomes (RLM) and to characterize the formed metabolites using LC-MS/MS. The study also established the precise and rapid HPLC and LC-MS/ MS method to separate, identify and characterize the formed Phase-I metabolites of belinostat.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of in vitro Metabolites of Belinostat by Rat Liver Microsomes using Ultra Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry

Grover¹,

Mehta²,

Naved³

et al. 2022

IJPER

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Objectives:The objective of the present study is to study the in-vitro metabolites of FDA approved anticancer drug, belinostat which is a histone deacetylase inhibitor. Methods: The metabolites were formed by incubating the drug, belinostat with rat liver microsomes, at 37°C for 24 hr. The newly formed metabolites were identified and characterized with the help of ultra-high performance liquid chromatography which is interlinked with tandem quadrupole time-of-flight mass spectrometry. Results: Two Phase-I metabolites were formed which include a belinostat amide (reductive metabolite) and belinostat acid (deaminated belinostat). We then elucidated the structures of the formed metabolites based on LC-MS/MS data which included accurate masses, the fragmentation of ions and chromatographic retention times. Conclusion: This study describes the detailed in-vitro metabolite profiling of belinostat which will be further helpful to predict the in-vivo metabolism of belinostat in the human body. Enzyme kinetic parameters (K m and V max ) for both the metabolites were also established using different substrate concentrations. The study will be helpful in determining the safety and efficacy of the drug. This will further help in determining the elimination mechanism of belinostat which in turn will assist in predicting the effectiveness and toxicity of the drug.

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“…[16][17][18][19][20][21][22][23][24][25][26] Separation, identification and characterization of degradation products of few anticancer drugs using the UPLC-MSMS technique have been reported. [27][28][29][30] HPLC is now an outdated technology in terms of sensitivity and cost-effectiveness. Till date, no study is reported on the degradation and stability of drugs under varied conditions such as hydrolytic, oxidative, thermal and photolytic.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of Novel and Highly Sensitive Stability-Indicating Reverse Phase UPLC Method for Quantification of Dabrafenib and its ten Degradation Products

Bhardwaj¹,

Mehta²,

Naved³

et al. 2022

IJPER

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Objectives: Dabrafenib is used as an active pharmaceutical ingredient acts as an inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth. In the current study, we focused on developing a robust, highly sensitive and stabilityindicating RP-UPLC method for estimation of DBR and its degradation products for the very first time. A stress study has been performed to demonstrate the stability-indicating capability of the method. Materials and Methods: Chromatographic separation was achieved using advanced UPLC technology with high resolution on Acquity BEH C-18 (100 mm × 2.1 mm, 1.8 μm) column using a mobile phase composed of orthophosphoric acid and methanol with very less consumption of solvents results in an eco-friendly method. Analysis was performed at 225 nm detector wavelength with 5 μL of injection volume and 0.3 mL min -1 of flow rate. Results: Forced degradation study was performed under hydrolytic (acid, alkali and neutral), oxidative, photolytic and thermal degradation as per ICH Q1 (R2) guidelines. The optimized method was observed to be linear in the concentration range of 12.5 to 125ng mL -1 with R 2 value of 1.0000. Conclusion: This is the first very sensitive stability-indicating UPLC method capable of separating dabrafenib and its ten degradation products at the nanogram (ng) level. The method was validated as stated by ICH guidelines.

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LC and LC–MS/MS studies for identification and characterization of new degradation products of ibrutinib and elucidation of their degradation pathway

Cited by 27 publications

References 8 publications

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

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

Identification and Characterization of in vitro Metabolites of Belinostat by Rat Liver Microsomes using Ultra Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry

Development and Validation of Novel and Highly Sensitive Stability-Indicating Reverse Phase UPLC Method for Quantification of Dabrafenib and its ten Degradation Products

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