Stress testing of linaclotide: Development of a validated stability-indicating RP-HPLC method

Acta Chromatographicae

Sree Rama Murthy Pyla¹  Prafulla Kumar Sahu¹  K. Srinivas² 

[1] 1Department of Pharmaceutical Analysis and Quality Assurance, Raghu College of Pharmacy, Dakamarri, Bheemunipatnam, Visakhapatnam-531 162, Andhra Pradesh, India;2Department of Pharmaceutical Analysis and Quality Assurance, Sri Vasavi Institute of Pharmaceutical Sciences, Tadepalligudem, West Godavari-534 101, Andhra Pradesh, India

关键词: degradation behavior;    linaclotide;    RP-HPLC;    stability-indicating;   

DOI  :  10.1556/1326.2017.29.2.05

学科分类：化学（综合）

来源: Akademiai Kiado Rt.

【 摘 要 】

Linaclotide, a first-in-class guanylate cyclase-C agonist, was recently approved by US Food and Drug Administration (FDA) as a promising pharmacotherapy for the management of constipation-predominant irritable bowel syndrome (IBS). In this communication, we present a novel stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method for the quantitative determination of linaclotide along with its degradation products. During the International Conference on Harmonization (ICH) prescribed stress study, linaclotide was found susceptible to degrade under hydrolytic (acid and base) and oxidative (peroxide) conditions. The separation of the degradants from the analyte was achieved on a Zorbax Eclipse XDB C8 Column (250 mm × 4.6 mm, 5 μm) using 0.01 N potassium dihydrogen orthophosphate buffer and acetonitrile (80:20 v/v) as mobile phase at a flow rate of 1.00 mL min−1 at column temperature of 40 °C. The detection of the column effluents was realized on a photodiode array detector set at 220 nm. Under the above optimal condition, the method was validated with respect to specificity, linearity, range, precision, robustness, and sensitivity in compliance to the regulatory requirements.

【 授权许可】

Unknown