Solubility determination of osimertinib mesylate in various solvents by validated, rapid, highly sensitive, water rich reverse phase high-performance liquid chromatography

This paper reports a simple, economical, rapid, highly sensitive, accurate, and precise water rich HPLC method for the determination of osimertinib mesylate. This method has been validated as per ICH norms. Separation of osimertinib mesylate was performed on commonly used reverse phase column (C-18, 5 μm, 150 × 4.6 mm) set at 25 °C and quantified by UV detection at 220 nm after isocratic elution from a water rich mobile phase (95:05 v/v of 0.1% aqueous phosphoric acid, pH 2.5:acetonitrile) flowing at a rate of 0.6 mL/min. A sharp and symmetrical peak of osimertinib mesylate was observed at 3.47 ± 0.01 min. The system suitability studies resulted in highly reproducible peaks with very low variation in peak areas and retention times (0.78 % and 0.30%, respectively) with excellent column efficiency (number of theoretical plates > 5000). The least square linear regression analysis (y = 21094 x + 35824) showed excellent correlation (r² = 0.999 ± 0.0006) between concentration and peak area of osimertinib mesylate through a wide concentration range of 0.58-150 ng/mL. The method was found to be very sensitive as evident from very low limits of detection and quantification values of 0.12 and 0.42 ng/mL, respectively. The assay or determinations were accurate, precise and reproducible with mean accuracy and mean relative standard deviation of precision of 102.16 ± 0.69 % and 0.63 ± 0.10%, respectively. The proposed method was used to determine solubility of osimertinib mesylate in various solvents such as polysorbates (Tweens), polyethylene glycol (PEG), propylene glycol monolaurate, propylene glycol monocaprylate, diethylene glycol monoethyl ether, ethanol and butenol, etc.