Development and Validation of Novel and Highly Sensitive Stability-Indicating Reverse Phase Ultra Performance Liquid Chromatography Method for Quantification of Ibrutinib and its ten Degradation Products

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

doi:10.36468/pharmaceutical-sciences.727

Cited by 12 publications

(6 citation statements)

References 16 publications

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“…A literature survey revealed no stability-indicating method yet reported for quantifying Ibrutinib in the finished dosage form (tablets and capsules) with proper evidence. Found a few LC methods to determine Ibrutinib in the solid dosage form and human plasma [1][2][3], details are shown in (Table 1). And remaining articles can see in reference [4][5][6][7][8][9][10][11][12].…”

Section: Ibrutinibmentioning

confidence: 99%

Development and validation of liquid chromatography method for determination of Ibrutinib in finished dosage forms using quality by design approach

Konduru

Gundla

Dongala

et al. 2022

Separation Science Plus

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A simple, precise, linear, robust, accurate, and stability‐indicating liquid chromatography method was developed and validated to determine Ibrutinib in finished solid dosage forms by reversed‐phase high‐performance liquid chromatography/photodiode array detector. Separation was achieved using a Luna C18 150 mm × 4.6 mm × 3.0 μm with a suitable mobile phase. The mobile phase: A consists of a 10 mM phosphate buffer concentration and 1 mL triethylamine, adjusted to pH 5.6 with a diluted orthophosphoric acid solution and acetonitrile in the ratio of 95:5 v/v to enhance the results. Moreover, mobile phase ‐ B contains 85% of acetonitrile. The optimized chromatographic conditions such as flow rate 1.0 mL/min, injection volume 10 μL, column temperature 40°C, and wavelength 258 nm. The proposed method is significant because it was developed by the Quality by Design approach. All impurities were identified, such as degradation and placebo impurities without interference at principle peak retention time. After development, it has been validated as per current regulatory guidelines. Obtained recovery between 98 and 102% at 50–200% level; linearity found (r2) = 0.9999 from 20 to 200% level; precision results achieved <2.0% relative standard deviation; and the robustness study results are found satisfactory. It's beneficial.

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Section: Ibrutinibmentioning

confidence: 99%

Development and validation of liquid chromatography method for determination of Ibrutinib in finished dosage forms using quality by design approach

Konduru

Gundla

Dongala

et al. 2022

Separation Science Plus

View full text Add to dashboard Cite

show abstract

“…[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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“…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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Development and Validation of Novel and Highly Sensitive Stability-Indicating Reverse Phase Ultra Performance Liquid Chromatography Method for Quantification of Ibrutinib and its ten Degradation Products

Cited by 12 publications

References 16 publications

Development and validation of liquid chromatography method for determination of Ibrutinib in finished dosage forms using quality by design approach

Development and validation of liquid chromatography method for determination of Ibrutinib in finished dosage forms using quality by design approach

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

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

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