Determination of related substances in the Intermediate M-Ⅰof relugolix by HPLC

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Author: WANG Fan ¹ LIU Min ¹ YANG Haixia ¹ ZHANG Zonglei ² LIU Yanxin ³ LIAN Zhenxia ¹ WANG Jing ¹  LI Xia ¹

Affiliation: 1.Analysis and Test Center, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, China 2.Institute of Chemical Drugs, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, China 3.Institute of Biological Drugs, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, China

Keywords: HPLC Related substances Intermediate M-Ⅰ of relugolix

DOI: 10.12173/j.issn.2097-4922.202605019

Abstract
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Abstract

Objective To establish a method for the determination of related substances in the Intermediate M-Ⅰof relugolix by HPLC.

Methods The HPLC method was performed on a Waters XBridge C₁₈ (250 mm×4.6 mm, 5 µm) column. Gradient elution was carried out using acetonitrile and phosphate buffer as the mobile phase at a flow rate of 1.5 mL/min. The column temperature was 30 ℃, the detection wavelength was 225 nm, and the injection volume was 20 μL.

Results The impurities in intermediate M-Ⅰof relugolix can be effectively detected. The detection limits of M-Ⅰ, 2,6-difluorobenzyl chloride, M-Ⅰ-SM, M-Ⅰ-intermediateⅠ, Impurity ZY1, Impurity 36, Impurity 45, and Impurity 46 were 0.059, 0.020, 0.035, 0.041, 0.055, 0.077, 0.062, and 0.054 µg/mL, and the quantification limits were 0.197, 0.099, 0.117, 0.136, 0.183, 0.257, 0.207, and 0.182 µg/mL. The main compound and the impurities were well separated, meeting the system suitability requirements. In the quantitative analysis, the main compound and the seven impurities all exhibited good linearity within their respective concentration ranges (r ≥ 0.999 0). The mean recoveries of the seven impurities ranged from 97.77% to 108.42%, with RSDs ≤ 2.11% (n=9).

Conclusion The established method demonstrates good specificity, high sensitivity and satisfactory accuracy, and is suitable for the determination of related substances in the Intermediate M-Ⅰ of relugolix.

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