目的:一种简单而可靠的顶空/气相色谱-火焰电离传感器(HS/GC/FIS)方法,用于痕量评估致癌杂质,氯甲烷,描述了盐酸曲美他嗪(TRD)的药物成分及其配方。
方法:此HS/GC/FIS方法基于对DB-624[75.0m-长度,0.53mm-内径,3.0μm-膜厚]柱使用氮气作为载气以3mL/min的流速流过该柱。在260℃的设定温度下用火焰离子化传感器检测洗脱的CH3Cl。
结果:优化的HS/GC/FIS方法学方法得到了彻底验证,证明它在5.0ppm至1508.4ppm的范围内呈线性关系,灵敏度高,检测限为1.65ppm,定量限为5.01ppm,重现性,RSD值为2.10-2.35%,准确,回收率为81.9-99.0%,相对于烤箱温度的变化,其百分比变化为7.5-12.22%,喷油器温度,检测器温度和实用的定期TRD质量控制。
结论:研究结果表明,通过这种优化的HS/GC/FIS方法学方法,可以成功测量TRD药物成分和制剂中的痕量致癌杂质(氯甲烷)。
OBJECTIVE: A simple and robust head space/gas chromatography with flame ionisation sensor (HS/GC/FIS) approach for the trace evaluation of carcinogenic impurity, methyl chloride, in trimetazidine dihydrochloride (TRD) drug ingredient and its formulation is described.
METHODS: This HS/GC/FIS approach was based on separation and analysis of CH3Cl content on DB-624 [75.0m - length, 0.53mm - internal diameter, 3.0μm - film thickness] column using nitrogen as carrier gas flowing through the column at 3mL/min stream rate. Detection of eluted CH3Cl was accomplished with flame ionization sensor at a set temperature of 260̊C.
RESULTS: The optimised HS/GC/FIS methodological approach was thoroughly validated, demonstrating that it was linear with range of 5.0ppm to 1508.4ppm, sensitive with detection limit of 1.65ppm and quantification limit of 5.01ppm, reproducible with RSD values of 2.10-2.35%, accurate with recoveries of 81.9-99.0%, robust with percent variation of 7.5-12.22% with respect to changes in oven temperature, injector temperature, detector temperature and practical for regular TRD quality control.
CONCLUSIONS: The findings revealed that with this optimised HS/GC/FIS methodological approach, the trace amounts of carcinogenic impurity (methyl chloride) in TRD drug ingredient and formulation could be successfully measured.