Quantification of Drospirenone- and Ethinyl Estradiol-Related Impurities in a Combined Pharmaceutical Dosage Form by a Chromatography Method With a QbD Robustness Study.

BACKGROUND: The estimation of drugs containing drospirenone (DRSP) and ethinyl estradiol (EE), and their related impurities, in low-dose oral contraceptive drug products is an extremely challenging target. The proposed research sought to develop and validate a stability-indicating method for quantifying drug substances and their related impurities in tablet formulation. OBJECTIVE: To develop and validate a simple, specific, accurate, precise, and stability-indicating reverse-phase (RP)-HPLC method for quantification of DRSP, EE, and their impurities in accordance with International Conference on Harmonisation (ICH) guidelines. METHOD: The separation was achieved using an Agilent Zorbax SB C18 column (4.6 mm × 250 mm, 5 µm) with a detection wavelength of 215 nm and mobile phases A (100% acetonitrile) and B (acetonitrile-water, 1 + 3, v/v) at a flow rate of 1.3 mL/min and a column temperature of 40°C. RESULTS: The recovery study of each impurity was conducted in the range of 24 to 72 µg/mL for DRSP-related impurities and 0.2 to 0.6 µg/mL for EE-related impurities with respect to the specification limit. A linearity study was conducted over a range of 1.5 to 90 µg/mL for DRSP and DRSP-related impurities, and 0.125 to 0.75 µg/mL for EE-related impurities. A Quality by Design (QbD) study demonstrated the method's robustness. CONCLUSIONS: As per current guidelines, a stability-indicating method has been developed for the determination of impurities in DRSP/EE film-coated tablets. A QbD-based robustness test was performed and the method was found to be robust. HIGHLIGHTS: An accurate, precise, stability-indicating, gradient RP-HPLC method has been developed and validated to determine DRSP, EE, and nine related impurities in tablet formulation. A QbD technique was used to establish a robustness study.

Novel reversed-phase HPLC method for simultaneous determination of ethynodiol diacetate (EDA)/ethinyl estradiol (EE) in pharmaceutical dosage form.

Ethynodiol diacetate (EDA) and ethinyl estradiol (EE) tablets are indicated to prevent pregnancy in women who use oral contraceptives as a contraception method. EDA and EE were separated by reversed-phase HPLC using Agilent ZORBAX SB-Phenyl column, 4.6 mm × 15 cm, 5 µm, using a gradient mixture of acetonitrile and Milli-Q water as mobile phase. The linearity and recovery were found in the range of 0.025-0.25 mg/mL and 0.05-0.18 mg/mL for EDA and 0.001-0.01 mg/mL and 0.002-0.007 mg/mL for EE, respectively. The method is validated according to the regulatory guidelines concerning system suitability, specificity, repeatability, recovery, linearity, robustness, and stability of the sample solution.