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YIN Lining, ZHANG Yu, HU Yiqiao, ZHAN Xin'an. GC-MS method for the determination of the genotoxic impurity chlorocyclohexane in trihexyphenidyl hydrochloride bulk drug[J]. Journal of China Pharmaceutical University, 2022, 53(1): 79-85. DOI: 10.11665/j.issn.1000-5048.20220112
Citation: YIN Lining, ZHANG Yu, HU Yiqiao, ZHAN Xin'an. GC-MS method for the determination of the genotoxic impurity chlorocyclohexane in trihexyphenidyl hydrochloride bulk drug[J]. Journal of China Pharmaceutical University, 2022, 53(1): 79-85. DOI: 10.11665/j.issn.1000-5048.20220112

GC-MS method for the determination of the genotoxic impurity chlorocyclohexane in trihexyphenidyl hydrochloride bulk drug

Funds: This study was supported by the National Natural Science Foundation of China (No.31872755,No.81872811), Jiangsu Outstanding Youth Fund (No.BK20190007) and the Central Fundamental Research Funds for the Central Universities (No.02141438473)
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  • Received Date: May 26, 2021
  • Revised Date: January 05, 2022
  • Gas chromatography-mass spectrometry (GC-MS) method was established for trace analysis of the potential genotoxic impurity chlorocyclohexane in trihexyphenidyl hydrochloride bulk drug, utilizing an RXI-5SIL MS column at isothermal temperature of 60 °C for the entire 6-minute run time.The inlet temperature was 180 °C and a split ratio of 10∶1 was used with the injection volume of 1.0 μL.The selective ion monitoring mode was set at m/z 82 for chlorocyclohexane with a detector voltage of 0.3 kV and an ion source temperature of 240 °C.The method was verified with respect to specificity, limit of detection (LOD), limit of quantitation (LOQ), accuracy, precision and robustness.Good linear correlation was achieved with coefficient r of 0.999 9 in the concentration range of 59.72-493 ng/mL.The intra- and inter-day precision was satisfactory (RSD ≤ 5.0%) and robust (RSD ≤ 1.65%).The proposed method in this study can be adequately adopted as a tool for quality assurance of trihexyphenidyl hydrochloride in routine test of potential genotoxic impurity.
  • [1]
    ?Expert Rev Clin Pharmacol,2008,1(2):241-250.
    [2]
    Bolt HM,Foth H,Hengstler JG,et al. Carcinogenicity categorization of chemicals-new aspects to be considered in a European perspective[J]. Toxicol Lett,2004,151(1):29-41.
    [3]
    Chinese Pharmacopoeia Commission. Chinese Pharmacopoeia:part 4 (中华人民共和国药典:四部)[S]. Beijing:China Medical Science Press,2020:527-530.
    [4]
    Katzenschlager R,Sampaio C,Costa J,et al. Anticholinergics for symptomatic management of Parkinson''s disease[J]. Cochrane Database Syst Rev,2003(2):CD003735.
    [5]
    Zhu ZY,Huang D. Process improvement on the synthesis of trihexyphenidyl hydrochloride[J]. China Med Pharm (中国医药科学),2016,6(9):53-55.
    [6]
    International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonized Guideline:assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk M7(R1)[S/OL].2017[2021-05-27].https://database.ich.org/sites/default/files/M7_R1_Guideline.pdf.
    [7]
    Liu DQ,Sun MJ,Kord AS. Recent advances in trace analysis of pharmaceutical genotoxic impurities[J]. J Pharm Biomed Anal,2010,51(5):999-1014.
    [8]
    Skett PW. Low-level Measurement of Potent Toxins[M/OL]//Analysis of Drug Impurities. Oxford,UK:Blackwell Publishing Ltd.,2007:82-123[2021-05-27]. https://doi.org/10.1002/9780470988749.ch4.
    [9]
    Tyner T,Francis J. ACS Reagent Chemicals (Specifications and Procedures for Reagents and Standard-Grade Reference Materials)[M/OL]. Washington,DC:American Chemical Society,2017[2021-05-27].https://doi.org/10.1021/acsreagents.2007.20160601.
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