Quality by Design-Based Development of a Robust LC Method for Simultaneous Estimation of Process- and Degradation-Related Impurities in Rifapentine Drug Product for the Treatment of Active and Latent Tuberculosis

基于质量源于设计的稳健液相色谱法开发,用于同时测定利福喷汀药物制剂中工艺相关杂质和降解相关杂质,该药物制剂用于治疗活动性和潜伏性结核病

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Abstract

A precise, robust, and stability-indicating liquid chromatographic (LC) method coupled with a photodiode array (PDA) detector was developed and validated for the quantitative estimation of rifapentine, an essential therapeutic agent for both active and latent tuberculosis (TB). The chromatographic separation was achieved on a YMC Pack C18 column (250 × 4.6 mm, 5 μm) using a gradient elution with Solvent A composed of phosphate buffer (pH 6.3) and acetonitrile (90:10, v/v), and Solvent B consisting of 100% acetonitrile. The optimized parameters included a flow rate of 1.0 mL min(-1), a column temperature of 30 °C, an injection volume of 25 μL, and UV detection at 330 nm. Method validation, conducted as per ICH Q2(R2) guidelines, confirmed excellent accuracy with recovery results between 97.0% and 103.0%. The method demonstrated linearity over a broad concentration range, from the limit of quantification (LOQ) to 200% of the target concentration, with correlation coefficients (R(2)) exceeding 0.998 for all impurities. Precision, expressed as relative standard deviation (RSD), was consistently below 5.0%. Forced degradation studies indicated that rifapentine undergoes degradation under acidic, basic, oxidative, thermal, and photolytic conditions, thus confirming the stability-indicating nature of the developed LC method.

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