Implementation of a single quad MS detector in routine QC analysis of peptide drugs

• Published in: Journal of pharmaceutical analysis 2016-02, Vol.6 (1), p.24-31
• Main Authors: D'Hondt, Matthias, Gevaert, Bert, Wynendaele, Evelien, De Spiegeleer, Bart
• Format: Article
• Language: English
• Subjects: HPLC-UV; Impurity profiling; Original; Peptide; Quality control; Single quad MS detector; 四极质谱; 多肽类药物; 检测器; 药物分析; 超高效液相色谱; 高效液相色谱柱; 高效液相色谱法
• ISSN: 2095-1779; 2214-0883
• DOI: 10.1016/j.jpha.2015.09.002

A newly developed single quad mass spectrometry （MS） detector was coupled to a ultra-high perfor- mance liquid chromatography （UPLC） system and implemented in the routine quality control （QC） and impurity analysis of four therapeutic peptides, namely bleomycin sulfate, tyrothricin, vancomycin HCl and bacitracin, which were selected given their multi-component drug nature and their closely struc- turally related impurity profiles. The QC and impurity profiling results obtained using the ultra-high performance liquid chromatography ultraviolet/mass spectrometry （UPLC-UV/MS） detection system were analyzed against the results obtained using traditional high performance liquid chromatography- ultraviolet detection （HPLC-UV） methods derived from pharmacopoeial methods. In general, the used stationary phases of sub-2 μm particle （UPLC） technology resulted in lower limits of detection and higher resolution separations, which resulted in more detected impurities and shorter overall run times con- trasting the traditional HPLC columns. Moreover, online coupling with a single quad MS detector allowed direct peak identification of the main compounds as well as small impurities, hereby increasing the information content without the need of reference standards.