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

Abstract

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.

Electrochemical Determination of Anti‐Cancer Drug Dabrafenib with High Sensitivity Using Multi‐Walled Carbon Nano Tubes Modified Glassy Carbon Electrode

“…[7] In the literature survey, numerous analytical methods have been developed for the quantitative analysis of Dabrafenib (DAB), including high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), fluorescence technique, and electrophoresis. [8][9][10][11][12][13][14][15][16][17][18][19][20] While these methods are effective and sensitive in detecting and quantifying DAB, they are often associated with drawbacks such as high costs and environmental concerns arising from the extensive use of organic solvents. Additionally, these methods may require lengthy analysis times and the expertise of trained professionals to operate analytical instruments effectively.…”

Identification and structural characterization of potential degradation products of baricitinib using liquid chromatography combined with quadrupole time-of-flight mass spectrometry

“…Advanced analytical techniques like reverse phase high performance liquid chromatography (RP-HPLC) coupled with tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR) spectroscopy are applied vastly for the detection and structure elucidation of all kinds of organic impurities [8,[10][11][12][13][14][15][16].…”

Development and Validation of a Stability-indicating Method for Neostigmine Bromide: Separation, Identification and Characterization of Degradation Product using LC-MS and ESI-Q-TOF-MS/MS

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Separation, identification and characterization of DPs of few anticancer drugs using the UPLC-MSMS technique have been reported. [25][26][27][28][29][30][31][32][33][34] Based on the recommendations of ICH guidelines Q3A (R2) and Q3B (R2), identification and characterization of all the DPs or process-related impurities of dabrafenib have been carried out. [35][36] But to date, no study is reported on the degradation and stability of drugs under varied conditions such as hydrolytic, oxidative, thermal and photolytic.…”