Chiral LC method
development for stereo-selective separation and quantification of Ivosidenib and
its S,R and R,R isomeric impurities in drug substance and finished product
Tatavarti Bhagya Kumar, Usha Rani N., Tangeti Venkata Swamy and Tulasi Bhavani K.
Res. J. Chem. Environ.; Vol. 29(4); 79-85;
doi: https://doi.org/10.25303/294rjce079085; (2025)
Abstract
A robust and reliable chiral HPLC method was developed and validated for the separation
and quantification of ivosidenib and its stereoisomeric impurities (S,R and R,R
forms) in pharmaceutical formulations and bulk drug samples. The study optimized
various analytical parameters including the mobile phase composition, pH modifiers,
flow rate, detector wavelength and column temperature. A mobile phase comprising
of methanol and 0.1% formic acid in 65:35 (v/v) ratio, with a flow rate of 0.8 mL/min
and a detection wavelength of 248 nm, was identified as optimal. These conditions
provided high-resolution symmetrical peaks with retention times of 6.5, 5.7 and
4.8 minutes for ivosidenib, S,R and R,R impurities respectively, ensuring a total
analysis time of 10 minutes. System suitability parameters including peak resolution
and retention time reproducibility, were within acceptable limits. Linearity studies
demonstrated a strong correlation (R² > 0.999) for ivosidenib (25–250 μg/mL) and
its impurities (0.25–2.50 μg/mL). Sensitivity analysis revealed detection limits
as low as 0.075 μL/mL for the impurities.
Accuracy studies across multiple concentrations showed recovery rates within 98–102%,
with low relative standard deviations, indicating the method's high precision and
reproducibility. Robustness testing confirmed the method's reliability. Stability
studies validated that ivosidenib and its isomeric impurities remained stable for
at least 15 days under both room temperature (25°C) and refrigeration (2°C) conditions.
The results demonstrated compliance with pharmacopoeial standards, with ivosidenib
content at 99.15% and impurity levels below the detection limit, confirming the
stereoselective efficiency of the formulation. The method’s reliability, simplicity
and applicability to both bulk batch and formulation samples make it an essential
tool for pharmaceutical quality assurance.
