Critical strategies to pinpoint carryover problems in liquid chromatography-mass spectrometry: A systematic direction for their origin identification and mitigation

[Display omitted] •Carryover unduly affects qualitative and quantitative analysis of organic compounds.•It can limit the dynamic range of LC-MS based quantitation method.•Highly sensitive mass detector needs substantially low carryover from LC system.•Finding source of carryover is the first and most critical step in its minimization.•Instrument design based strategy fasten the process of carryover mitigation. Carryover has always been an issue in trace level quantification of compounds. It can limit the dynamic range of the quantitation method required to get it fit into the regulatory acceptance criteria. Carryover adversely affects the liquid chromatography-mass spectrometry (LC-MS) based accurate quantification of incurred samples. Furthermore, today’s highly sensitive mass detector is driving a need for substantially low carryover from LC system. Finding the source of carryover is the first and most critical step in the elimination of carryover. In this review, we have proposed a systematic approach to track the origin of carryover in LC-MS and suggested logical approaches to eliminate it. We have included an extensive discussion related to the impact of instrument designs on carryover. The article will be useful to the researchers working in trace level quantification of small as well as large molecules using LC-MS. The approaches and logical paths demonstrated in this manuscript will be helpful to fasten the process of carryover mitigation in LC-MS. It will reduce the time and resources required in the minimization or elimination of carryover problem.