Method for Heterogeneous Sample Analysis on LCMS Without Sample Manipulation

27 August 2019, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


We describe a simple, effective, and automated method that tolerates heterogeneous sample analysis on liquid chromatography mass spectrometer (LCMS) systems without any sample manipulation. This was developed to mitigate the inconsistent sample preparations that often arise when LCMS systems are operated in a self-service mode (walkup or open access), such as in a pharmaceutical research environment. We demonstrated the robustness of our method through 144 sequential injections of a heterogeneous sample on the LCMS without observing clogging or an increase in the system pressure, whereas with a conventional set-up, the same sample resulted in an almost instantaneous clog. Analysis of carefully tracked metrics for six walkup LCMS over 3 years since the rollout of this method at our facility has shown > 95% sustained reduction in clogging rate, accompanied by over a 30-fold increase in operational robustness, all with no impact on the quality of the chromatography. Implementation has further lead to savings in time and resources for both the system administrators and users, hence making walk-up LCMS easier to use yet harder to break, with the additional benefit of providing data for heterogeneous samples available to the user, and reducing sample carry-over. The method is inexpensive to implement and requires neither expensive hardware such as pumps or valves, nor any changes to existing LCMS methods.


heterogeneous sampling
reversed phase high performance liquid chromatography
Open Access Method
reaction monitoring experiment
sample analysis


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