GC-MS法测定盐酸苯海索原料药中遗传毒性杂质氯代环己烷
GC-MS method for the determination of the genotoxic impurity chlorocyclohexane in trihexyphenidyl hydrochloride bulk drug
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摘要: 建立一种GC-MS分析方法用于盐酸苯海索原料药中遗传毒性杂质氯代环己烷的含量测定。采用SH-RXI-5SIL MS毛细管柱（0.25 mm × 30 m，0.25 μm），以60 ℃恒温程序运行6 min；进样口温度180 ℃，进样分流比为10∶1，进样量为1.0 μL；质谱检测器采用SIM检测模式，检测器电压为0.3 kV，接口温度240 ℃，选择性监测m/z 82离子。氯代环己烷在59.72 ~1 493 ng/mL范围内与峰面积呈现良好的线性关系（r = 0.999 9）；检测限和定量限浓度分别为17.92和59.72 ng/mL；该方法日内和日间精密度良好（RSD ≤ 5.0%）且耐用性良好（RSD ≤ 1.65%）。本法适用于盐酸苯海索中遗传毒性杂质氯代环己烷的痕量检测，可为盐酸苯海索原料药的质量控制提供理论依据。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.
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Keywords:
- trihexyphenidyl hydrochloride /
- chlorocyclohexane /
- genotoxic impurity /
- GC-MS /
- trace analysis
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