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

YIN Lining; ZHANG Yu; HU Yiqiao; ZHAN Xin'an

doi:10.11665/j.issn.1000-5048.20220112

Journal of China Pharmaceutical University > 2022 > 53(1): 79-85. > DOI: 10.11665/j.issn.1000-5048.20220112

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

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

1.
School of Life Sciences, Nanjing University, Nanjing 210093
2.
Hisun Pharmaceutical (Hangzhou) Co., Ltd., Hangzhou 311404, China

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

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Abstract

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.
- trihexyphenidyl hydrochloride,
- chlorocyclohexane,
- genotoxic impurity,
- GC-MS,
- trace analysis

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

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