HPLC法测定盐酸右美托咪定有关物质

目的:建立反相高效液相色谱法分离测定盐酸右美托咪定及其有关物质。方法:采用Welch Ultimate AQ C₁₈(250 mm×4.6 mm,3 μm)为色谱柱,柱温35 ℃;以乙腈-磷酸盐缓冲液为流动相,进行梯度洗脱;流速为1.0 mL·min^-1;检测波长为220 nm。结果:盐酸右美托咪定与各已知杂质及强制破坏产生的降解产物均分离良好;杂质A、B、C、D、E、F和G在各自的线性范围内质量浓度与峰面积呈良好的线性关系(r ≥ 0.999 5,n=6),且校正因子(相对于盐酸右美托咪定)分别为1.73、1.55、0.98、1.45、0.92、0.98、1.04;上述杂质的平均回收率(n=9)分别为116.7%、100.4%、102.6%、92.0%、108.1%、109.0%、84.2%,RSD分别为2.0%、1.3%、1.8%、7.2%、1.4%、2.3%、2.1%;精密度试验RSD(n=6)分别为1.7%、0.55%、0.41%、1.8%、0.46%、0.76%、0.50%。经检测表明,3批终产品均未检出杂质,粗品中主要杂质为杂质C(同分异构体)和杂质F(C4,C5-二烷基化物)。结论:本法经方法学验证,可用于盐酸右美托咪定有关物质的检测。

Objective:To develop an HPLC method for the separation of dexmedetomidine hydrochloride and determination of its known related substances.Methods:The analysis was conducted on a Welch Ultimate AQ C₁₈ column (250 mm×4.6 mm,3 μm) with a mobile phase of acetonitrile - phosphate buffer by gradient elution at the flow of 1.0 mL·min^-1.The column temperature was 35 ℃ and the detection wavelength was 220 nm.Results:The known impurities and degraded products by forced destruction were completely separated from dexmedetomidine.The calibration curves of seven known impurities (A,B,C,D,E,F and G) were linear in the self-concentration range(r ≥ 0.999 5,n=6)and the correction factors were 1.73,1.55,0.98,1.45,0.92,0.98 and 1.04(with reference to dexmedetomidine hydrochloride),respectively;the average recovery rates(n=9)were 116.7%,100.4%,102.6%,92.0%,108.1%,109.0%,84.2%,respectively;RSDs were 2.0%,1.3%,1.8%,7.2%,1.4%,2.3%,2.1%,respectively.The RSDs of precision(n=6)of the above compounds were 1.7%,0.55%,0.41%,1.8%,0.46%,0.76%,and 0.50%,respectively.Our results showed that no impurity was detected in three batches APIs,and the impurity profile of crude product showed that the main impurities were impurity C(isomer) and impurity F (C4,C5-dialkylated compound).Conclusion:The established method is specific,accurate and sensitive,which is suitable for the determination of related substances in dexmedetomidine hydrochloride.