Determination of ethylene oxide genotoxic impurity in metoprolol succinate

doi:10.19803/j.1672-8629.20230071

Abstract

Abstract: Objective To establish an HPLC method for the determination of ethylene oxide genotoxic impurity XI in metoprolol succinate. Methods The Wondasil C18-WR (4.6 mm×250 mm, 5.0 μm) column was used. The mobile phase consisted of methanol and buffer (potassium dihydrogen phosphate 2.72 g, sodium perchlorate monohydrate 6.13 g, dissolved in 1 000 mL water, with pH adjusted to 6.0 with 1. 0 mol·L-1 sodium hydroxide solution) under gradient elution. The flow rate was 1.0 mL·min-1, the injection volume was 40 μL, the column temperature was 30℃ and the detection wavelength was 226 nm. Results The linear range of impurity XI was 0.853 2 to 6.818 3 μg·mL-1(r=0.999 9). The detection limit was 0.426 1 μg·mL-1, with a quantitative limit of 0.852 3 μg·mL-1. The average recovery was 94.21%. Conclusion This method is highly specific, sensitive and user-friendly, which can be used for the determination of genotoxic impurity of ethylene oxide in metoprolol succinate.

Key words: metoprolol succinate, ethylene oxide derived glycol ethers, genotoxic, impurity, gradient elution, content determination, high performance liquid chromatography( HPLC), highly specific

CLC Number:

R917

LIU Chunliang, LIU Xiaoqiong, ZHANG Lei, ZHU Kexu, CAO Jieyong, WANG Chen, XU Mingzhe, ZHANG Xianhua. Determination of ethylene oxide genotoxic impurity in metoprolol succinate[J]. Chinese Journal of Pharmacovigilance, 2023, 20(4): 370-373.

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