Separate quantification of anastrozole and letrozole by a novel stability‐indicating ultra‐fast LC method

Abstract

A unified stability‐indicating method has been proposed using standardized ultra‐fast liquid chromatography conditions applicable to quantification of both anastrozole and letrozole in low dose pharmaceutical tablets. The drugs were subjected to chromatography one at a time following forced degradation at accelerated stress conditions. Separation of the main analyte from the possible degradation products was achieved on a Waters Aquity BEH C18 (50 × 2.1 mm; 1.7 µm) column maintained at 40°C with gradient elution of mobile phase comprising solvent A (0.1% orthophosphoric acid and acetonitrile [70:30 v/v]) and solvent‐B (0.1% orthophosphoric acid and acetonitrile [30:70 v/v]) at a flow rate of 0.35 mL/min. Photo diode array detection of anastrozole and letrozole was made at 215 and 236 nm, respectively. The stress testing demonstrated that both the drugs are susceptible to degrade by base hydrolysis and oxidation. The method was also applied for cleaning validation (residue analysis) at 0.5 µg with a limit of quantification > 10 S/N for 0.1 µg of both drugs. The recovery assessed on two different surfaces of cGMP area (Stainless steel and Class‐A Glass) was satisfactory.