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The application of sub‐2‐μm particle liquid chromatography‐operated high mobile linear velocities coupled to orthogonal accelerated time‐of‐flight mass spectrometry for the analysis of ranitidine and its impurities
Author(s) -
Jones Michael D.,
Plumb Robert S.
Publication year - 2006
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.200600118
Subject(s) - chromatography , mass spectrometry , impurity , chemistry , active ingredient , time of flight mass spectrometry , high performance liquid chromatography , resolution (logic) , analytical chemistry (journal) , computer science , bioinformatics , organic chemistry , ion , artificial intelligence , biology , ionization
Impurity profiling of pharmaceutical drug substances or dosage formulations require methods involving high sensitivity and resolution from LC and MS alike as well as an acceptable analysis time. While throughput can be increased, it is usually at the expense of chromatographic resolution. The application of sub‐2‐μm stationary phases and high mobile linear velocities has been combined with orthogonal acceleration (oa)‐TOF MS for the impurity structural characterization analysis of small‐molecule pharmaceutics. A pharmaceutical drug substance was forcefully degraded and used to test the proof of concept of developing an impurity profile method by ultra performance liquid chromatography (UPLC). Optimum conditions were identified by use of method development simulation software as well as traditional approaches of method scouting with columns and a varied range of pH. Further analysis illustrated the effectiveness of applying oa‐TOF MS techniques to assist in achieving exact mass coupled with MS/MS to define the structural characterization of the related substances relative to the pharmaceutical active ingredient and identification of any unknown impurity substances. The barriers with trade‐offs between resolution and speed are overcome by the application of UPLC, whereas the increased sensitivity provides for superior exact mass oa‐TOF MS.