A novel two-dimensional liquid chromatography - Mass spectrometry method for direct drug impurity identification from HPLC eluent containing ion-pairing reagent in mobile phases

作者：Long, Zhen; Zhan, Zhaoqi; Guo, Zhimou^*; Li, Yueqi^*; Yao, Jinting; Ji, Feng; Li, Changkun; Zheng, Xin; Ren, Biao; Huang, Taohong

来源：Analytica Chimica Acta, 2019, 1049: 105-114.

DOI：10.1016/j.aca.2018.10.031

• Two dimensional liquid chromatography
• Ion-pairing reagent
• Non-volatile
• Mass spectrometry
• Generic drug
• Impurity

In this study, a novel two dimensional liquid chromatography - mass spectrometry (2D-LC-MS) method with use of a weak anion exchange column between the 1st DLC RP column and the 2nd DLC RP column (RP1-WAX-RP2) was developed and applied to identify drug impurities from MS incompatible mobile phases containing sodium 1-octanesulfonate and non-volatile buffer. The 1st DLC conditions follow exactly the original standard HPLC method recorded in Chinese Pharmacopeia (ChP), European Pharmacopeia (EP) or US Pharmacopeia (USP). An impurity fraction was collected with a built-in sample loop (100 mu L) and transferred to the WAX column where 1-octanesulfonate and phosphate were trapped and removed. While, the impurity and other cations were eluted to the 2nd D column (RP2) for separation and identification by connected IT-TOF MS. Methods were programmed and applied to identify impurities in two generic drugs, sulpiride (hydrophilic drug with logP 0.57) and dobutamine (hydrophobic drug with logP 3.6). The results indicate that the methods based on RP1-WAX-RP2 column configuration offer a feasible solution for direct impurity identification in generic drug product or API without needs of off-line desalting from the MS incompatible mobile phases containing ion-pairing reagent and nonvolatile buffer.

• 出版日期2019-2-21
• 单位中国科学院; 中国科学院大连化学物理研究所