SIMPLE AND SENSITIVE ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF SETMELANOTIDE BY RP-HPLC

Amit Shinde*

ABSTRACT

Setmelanotide, a novel melanocortin-4 receptor (MC4R) agonist, has emerged as a promising therapeutic agent for rare genetic disorders of obesity. Accurate and reliable quantification of Setmelanotide in pharmaceutical formulations and biological matrices is essential for its quality control and pharmacokinetic studies. This review focuses on the development and validation of a simple, sensitive, and robust reverse-phase high-performance liquid chromatography (RP-HPLC) method for the estimation of Setmelanotide. Various parameters including mobile phase composition, detection wavelength, flow rate, and column selection were optimized to achieve high resolution and reproducibility. The method was validated according to ICH guidelines, assessing parameters such as linearity, accuracy, precision, specificity, limit of detection (LOD), and limit of quantification (LOQ). The developed RP- HPLC method demonstrated excellent linearity in the therapeutic range, high sensitivity with low LOD/LOQ values, and satisfactory precision and accuracy. The review highlights the suitability of this method for routine analysis and quality assessment of Setmelanotide in pharmaceutical research and development. Setmelanotide, a selective melanocortin-4 receptor (MC4R) agonist, represents a novel therapeutic option for managing rare genetic disorders of obesity. Given its clinical significance, a reliable and sensitive analytical method is essential for routine quality control, formulation analysis, and pharmacokinetic evaluation. This study reviews the development and validation of a reverse-phase high-performance liquid chromatography (RP-HPLC) method for the quantitative estimation of Setmelanotide. Method optimization focused on selecting a suitable mobile phase composition, flow rate, detection wavelength, and column parameters to achieve high resolution and peak symmetry. The method was validated in accordance with ICH Q2 (R1) guidelines, demonstrating excellent linearity (R² > 0.999), accuracy (recovery 98–102%), and precision (RSD < 2%). Sensitivity was confirmed with low limits of detection (LOD) and quantification (LOQ), ensuring applicability even at trace levels. The proposed RP-HPLC method offers a simple, cost-effective, and robust approach for the routine analysis of Setmelanotide in pharmaceutical formulations and research environments.

Keywords: Setmelanotide, RP-HPLC, method development, validation, ICH guidelines, obesity, MC4R agonist.