The Novel Quality by Design Concept in the Development and Validation of a Stability-Indicating RP-HPLC PDA Method for Estimating Terlipressin in an Injectable Dosage Form

The research presents a novel application of the QbD technique to develop and validate a stability-indicating method for terlipressin quantification in injection form, aligning with ICH Q2 (R2) guidelines using the HPLC method. Terlipressin, a synthetic drug recently approved by the FDA for treating hepatorenal syndrome, lacks an official monograph in any pharmacopeia, and the existing stability indicating methods for its quantification were limited. The primary objective is to establish a method using the QbD approach and ICH Q8 (R2) guidelines, emphasizing accuracy, simplicity, rapidity, and robustness. The method is optimized through the design of experiments, including response surface plots, contour plots, and overlay plots. Successful development of this method results in a shorter retention time (less than 4 min) using a SunFire C₁₈ column with dimensions 250 mm × 4.6 mm and particle size of 5µm, mobile phase consisting of acetonitrile and 0.1% orthophosphoric acid (11:89 v/v), flow rate of 1 ml/min, and the PDA detection at 216 nm, with an injection volume of 8 µl and a column heater temperature of 30 °C. This method’s total run time was 6 min, using water as a diluent. Forced degradation experiments have verified that the approach is stability-indicating for the terlipressin injection dosage form assay. The analytical method has demonstrated a linear response over the 0.25–1.5 µg/ml concentration range, exhibiting an R² of 0.9994 and recovery percentage was 99.09–100.43%.