琥珀酸曲格列汀及其有关物质的UPLC Orbitrap HRMS法测定

Determination of Trelagliptin Succinate and Related Substances by UPLC Orbitrap HRMS

建立了超高效液相色谱-静电场轨道阱高分辨质谱(UPLC Orbitrap HRMS)法测定琥珀酸曲格列汀(1)原料药及其中间体2以及位置异构体3。采用Eclipse Plus-C_(18)色谱柱,以0.05 mol/L的乙酸铵缓冲液∶乙腈(45∶55)为流动相。质谱采用加热电喷雾离子源,正离子扫描模式,扫描范围m/z 200~500,监测离子分别为[M+H]^+m/z 358.167±0.003(1)、[M+H]^+m/z 294.044±0.003(2)、[M+H]^+m/z 358.167±0.003(3)。1琥珀酸盐在100~5 000 ng/ml范围内线性关系良好,有关物质2和3在1~50 ng/ml范围内线性关系良好,平均回收率分别为99.48%、97.51%和97.22%,RSD分别为1.63%、1.94%和2.17%;检测限均为0.01 ng/ml。本法定性可靠,定量准确,灵敏度高。

An ultra-high performance liquid chromatography Orbitrap high resolution mass spectrometry （UPLC Orbitrap HRMS） method was established for the determination of trelagliptin （1） succinate and its related substances （2 and 3）. A Eclipse Plus-Cl8 column was used, with the mobile phase of 0.05 mol/L ammonium acetate buffer ; acetonitrile （45：55）. The HESI was employed, as the sample was analyzed in the positive mode, with the scan mode of m/z 200 to m/z 500 and the monitoring ions of [M＋H] m/z 358.167＋0.003 （1）, [M＋H]m/z 294.044±0.003 （2）, [M＋H]m/z 358.167±0.003 （3）, respectively. It was linear for trelagliptin succinate in the range of 100±5 000 ng/ml, and for the related substances 2 and 3 in the range of 1-50 ng/ml. Their average recoveries were 99.48%, 97.51% and 97.22%, with RSDs of 1.63%, 1.94% and 2.17%, respectively. Their limits of detection was 0.01 ng/ml. The proposed method was simple, accurate and sensitive.