Safety Monitoring

Determination of genotoxic impurities methyl isoquinoline-5-sulfonate and ethyl isoquinoline-5-sulfonate in fasudil hydrochloride by Q-Orbitrap high resolution mass spectrometry*

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  • 1. KPC Pharmaceuticals,Inc,Kunming 650100,China;
    2. Dali University,Dali 671000,China;
    3. Yunnan University of Traditional Chinese Medicine,Kunming 650500,China

Revised date: 2020-11-19

  Online published: 2024-05-31

Abstract

Objective: To establish an HPLC-Q-Orbitrap method to determine the contents of genotoxic impurities methyl isoquinoline-5-sulfonate and ethyl isoquinoline-5-sulfonate in fasudil hydrochloride. Methods: The separation was performed on a Thermo Scientific Hypersil GOLD C8 column(4.6 mm×150 mm,3 μm)using the mobile phase consisting of acetonitrile(mobile phase A)and 0.1% formic acid aqueous solution(mobile phase B)by gradient elution at a flow rate of 0.9 mL·min-1.The column temperature was set at 30 ℃.The analytes were detected by Q-Orbitrap high resolution mass spectrometry with ESI source in positive mode.The detection was achieved in Full MS-SIM mode,and the scan range was set at m/z 223-239.The extracted ion chromatograms were used for the quantitation,selecting m/z 224.037 59(mass tolerance<5×10-6)and m/z 238.053 24(mass tolerance<5×10-6)as the quantitative ions of methyl isoquinoline-5-sulfonate and ethyl isoquinoline-5-sulfonate, respectively. Results: Methyl isoquinoline-5-sulfonate and ethyl isoquinoline-5-sulfonate showed good linear relationships within the range of 1.0-30 ng·mL-1(r=0.998 3 and 0.999 0,respectively).The limit of detection and limit of quantification for methyl isoquinoline-5-sulfonate was 0.66 μg·g-1 and 2.0 μg·g-1,respectively.The limit of detection and limit of quantification for ethyl isoquinoline-5-sulfonate was 0.30 μg·g-1 and 1.0 μg·g-1,respectively. The spike recoveries(n=6)of the two compounds were 95.4% and 97.1%,with RSD of 2.1% and 1.9%, respectively.The two genotoxic impurities were not detected in 6 batches of samples. Conclusion: The established method is simple,rapid,accurate and sensitive,and can be used for the quality control of fasudil hydrochloride.

Cite this article

LIU Yang, LI Jian-feng, LI Ning, CHEN Yun-jian, LIU Shi-cheng, YANG Zhao-xiang . Determination of genotoxic impurities methyl isoquinoline-5-sulfonate and ethyl isoquinoline-5-sulfonate in fasudil hydrochloride by Q-Orbitrap high resolution mass spectrometry*[J]. Chinese Journal of Pharmaceutical Analysis, 2021 , 41(1) : 154 -159 . DOI: 10.16155/j.0254-1793.2021.01.19

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