A new non-targeted screening strategy was developed for the detection and relative quantification of known and potentially unknown drug-related impurities in the active pharmaceutical ingredient daptomycin using ultra-high performance liquid chromatography, coupled with hybrid triple quadrupole-linear ion trap electrospray ionization mass spectrometry in three different modes. The precursor ion scan mode was first applied using the m/z transitions of 159.2, 313.2, and 341.2 for rapid screening of all daptomycin-related impurities. Precursor ions detected at specific retention times were selected, fragmented, and focused in enhanced product ion scan mode to obtain secondary ion mass spectra and identify drug-related impurities. Finally, each potential compound was relatively quantified in multiple reaction monitoring mode. Repeatability experiments suggest that this impurity profiling method is a reliable strategy for identifying unknown impurities in daptomycin and other drugs.

开发了一种新的非靶向筛选策略，使用超高效液相色谱结合三重四极杆线性离子阱电喷雾电离质量对活性药物成分达托霉素中已知和可能未知的药物相关杂质进行检测和相对定量三种不同模式的光谱测量。首先使用m/z应用母离子扫描模式159.2、313.2 和 341.2 的跃迁用于快速筛选所有达托霉素相关杂质。在特定保留时间检测到的前体离子被选择、碎裂并在增强型子离子扫描模式下聚焦，以获得二次离子质谱图并识别与药物相关的杂质。最后，在多反应监测模式下对每种潜在化合物进行了相对定量。重复性实验表明，这种杂质分析方法是鉴定达托霉素和其他药物中未知杂质的可靠策略。