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目的:建立测定盐酸倍他司汀片中乙烯吡啶、2-羟乙基吡啶、N-甲基-2吡啶乙胺等有关物质的检查方法。方法:采用高效液相色谱法,以十八烷基硅烷键合硅胶为填充剂,以缓冲液(称取醋酸铵0.69 g,用1 000 m L水溶解,以冰醋酸调节p H至4.7后,再加4.43 g十二烷基硫酸钠溶解,脱气)-乙腈(60∶40)为流动相,流速1.0 m L·min-1,检测波长259 nm,柱温40℃。结果:各杂质与主成分能完全分离,乙烯吡啶、2-羟乙基吡啶、N-甲基-2吡啶乙胺最低检测限(S/N=3)分别为0.4、0.4、4 ng,回收率分别为97.9%、98.1%、101.7%,浓度与峰面积均呈线性(r>0.999)。4个生产企业119批样品检验,共检出已知杂质2个(2-羟乙基吡啶、N-甲基-2吡啶乙胺)及未知杂质6个,各批次间检查的杂质个数及杂质量不同:2-羟乙基吡啶、N-甲基-2吡啶乙胺含量分别为0.005%~0.47%、0.040%~1.26%,总杂质量在0.2%~5.3%范围内。结论:本文建立的方法符合方法学验证要求,可用于盐酸倍他司汀有关物质检查。根据样品检测结果,建议将总杂质量定为2%。
OBJECTIVE: To establish a method for the determination of related substances such as vinylpyridine, 2-hydroxyethyl pyridine and N-methyl-2-pyridylethylamine hydrochloride in betahistine hydrochloride tablets. Methods: High performance liquid chromatography with octadecylsilane bonded silica as a filler, with buffer (weighed 0.69 g of ammonium acetate, dissolved with 1 000 m L of water, with acetic acid to adjust p H to 4.7 , Followed by 4.43 g sodium dodecyl sulfate dissolved, degassed) -acetonitrile (60:40) as mobile phase at a flow rate of 1.0 mL · min-1. The detection wavelength was 259 nm and the column temperature was 40 ℃. Results: The impurities could be completely separated from the main components. The minimum detectable limits (S / N = 3) of vinylpyridine, 2-hydroxyethyl pyridine and N-methyl-2-pyridylethylamine were 0.4, 0.4 and 4 ng respectively The rates were 97.9%, 98.1% and 101.7%, respectively. The concentrations and peak areas were linear (r> 0.999). Four batches of 119 batches of samples were tested and two known impurities (2-hydroxyethyl pyridine, N-methyl-2-pyridylethylamine) and 6 unknown impurities were detected. The number of impurities The results showed that the content of 2-hydroxyethyl pyridine and N-methyl-2-pyridylethylamine were 0.005% -0.47%, 0.040% -1.26% and 0.2% -5.3% respectively. Conclusion: The method established in this paper meets the validation requirements of methodology and can be used for the related substances examination of betahistine hydrochloride. According to the sample test results, it is recommended that the total amount of impurities set at 2%.