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Background <p>Sovateltide (SOVA) is a peptide-based therapeutic whose quality and safety depend on the accurate detection of related substances (RS). During hydrolysis studies, eight degradants were identified, which compromised the method’s selectivity. The co-elution of these degradants with the active pharmaceutical ingredient (API) and established impurities indicated that the initial approach was not stability-indicating.</p> Purpose <p>The study aimed to develop a robust, stability-indicating analytical method for SOVA using an Analytical Quality by Design (AQbD) approach, enabling reliable detection of RS, including chiral isomeric impurities formed during degradation.</p> Methods <p>Critical method attributes (CMAs) and critical method variables (CMVs) were systematically evaluated through the design of experiments (DoE). Resolution was defined as the CMA, while mobile phase pH, column temperature, column selection, gradient slope, and flow rate were CMVs. Screening using DoE identified a mobile phase (MP) pH of 2.5 and selected the YMC Meteoric Core C18 BIO column. Global optimisation was performed using Response Surface Methodology (RSM), with trifluoroacetic acid (TFA) concentration and column oven temperature as key factors. Monte Carlo simulations and capability analysis further refined the design space.</p> Results <p>The optimised method included TFA at 0.07% v/v in both mobile phases, a column oven temperature of 53 °C, 47% MP B at 35 minutes, and a flow rate of 0.5 mL min⁻¹. Key resolutions between chiral isomeric impurities and the SOVA peak were achieved. Six chiral impurities formed during base hydrolysis were identified as a significant outcome. The method demonstrated robustness, reliability, and transferability for routine quality control applications.</p> Conclusion <p>The AQbD-based approach enabled the development of a stability-indicating HPLC method for SOVA, ensuring precise detection of related substances, including chiral isomeric impurities, and providing a robust analytical method for quality control laboratories and the greenness of the current method was evaluated using enhanced tools.</p>

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A Simple and Robust Stability Indicating RP HPLC Method for Sovateltide Related Substances-Developed Using AQbD Approach

  • 期刊论文

  • 发表日期：

    2026年1月8日

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  • Ajit Hanumant Chandgude,
  • Ravinder Reddy Patlolla,
  • Archana Damle,
  • Ravindar Rendla,
  • Jayvant Harlikar,
  • Linga Banoth

摘要

Background

Sovateltide (SOVA) is a peptide-based therapeutic whose quality and safety depend on the accurate detection of related substances (RS). During hydrolysis studies, eight degradants were identified, which compromised the method’s selectivity. The co-elution of these degradants with the active pharmaceutical ingredient (API) and established impurities indicated that the initial approach was not stability-indicating.

Purpose

The study aimed to develop a robust, stability-indicating analytical method for SOVA using an Analytical Quality by Design (AQbD) approach, enabling reliable detection of RS, including chiral isomeric impurities formed during degradation.

Methods

Critical method attributes (CMAs) and critical method variables (CMVs) were systematically evaluated through the design of experiments (DoE). Resolution was defined as the CMA, while mobile phase pH, column temperature, column selection, gradient slope, and flow rate were CMVs. Screening using DoE identified a mobile phase (MP) pH of 2.5 and selected the YMC Meteoric Core C18 BIO column. Global optimisation was performed using Response Surface Methodology (RSM), with trifluoroacetic acid (TFA) concentration and column oven temperature as key factors. Monte Carlo simulations and capability analysis further refined the design space.

Results

The optimised method included TFA at 0.07% v/v in both mobile phases, a column oven temperature of 53 °C, 47% MP B at 35 minutes, and a flow rate of 0.5 mL min⁻¹. Key resolutions between chiral isomeric impurities and the SOVA peak were achieved. Six chiral impurities formed during base hydrolysis were identified as a significant outcome. The method demonstrated robustness, reliability, and transferability for routine quality control applications.

Conclusion

The AQbD-based approach enabled the development of a stability-indicating HPLC method for SOVA, ensuring precise detection of related substances, including chiral isomeric impurities, and providing a robust analytical method for quality control laboratories and the greenness of the current method was evaluated using enhanced tools.