A novel UPLC-PDA isocratic method for the quantification fulvestrant in oil-based pre-filled syringe injection matrix formulations

Abstract

Abstract Background Fulvestrant is a new estrogen receptor antagonist available in the market globally for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women. Methods The chromatographic separation of fulvestrant was carried out by using ACQUITY UPLC and a BEH Shield RP18, 50 mm × 2.1 mm, i.d 1.7-μm column with a prepared mobile phase consisting of water, acetonitrile, and methanol in the ratio of 300:400:300 (v/v/v), respectively. 1.0 mL orthophosphoric acid was added to the prepared mobile phase. The wavelength for detection was made at 220.0 nm using a PDA-UV detector with a flow rate of 0.3 mL min− 1. Results The system suitability parameters were found within the limits. The coefficient of correlation was found not less than 0.999. The percent recoveries of fulvestrant from 80, 100, to 120% levels are 100.1, 100.4, and 99.7 respectively. The LOD (0.51 μg mL− 1) and LOQ (1.54 μg mL− 1) values from the study demonstrate that the method is sensitive. The samples were subjected to forced degradation conditions of acidic and alkaline hydrolysis, oxidation, photolysis, metallic and thermal degradation in all conditions; peak was found pure (purity angle less than that of threshold). Conclusion A rapid, simple, stability-indicating, and validated RP-UPLC method was developed with 6 min of run time for the quantification of fulvestrant in oil-based injection formulations. This is the first stability-indicating method with the capability of resolving all the fulvestrant degradation impurities in the drug products. The method was validated for system suitability, linearity, precision, accuracy, specificity, intermediate precision, ruggedness, robustness, and solution stability.

Keywords

• Fulvestrant
• Method development
• Validation
• UPLC method
• Stability indicating
• Injections