New analytical platforms have been developed in response to the need for attaining increased peak capacity for multicomponent complex analysis with higher sensitivity and characterization of the analytes, and high-throughput capabilities. This review outlines the fundamental principles of target and comprehensive 2D LC method development and encompasses applications of LC-LC and LC × LC coupled to MS in bioanalysis using a variety of online analytical procedures. It also provides a rationale for the usage of the most employed mass analyzers and ionization sources on these platforms.
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