Troubleshooting LC-MS/MS: Identifying Method Problems and Building Robustness (Half Day)


Sunday, July 28, 2024
1:30 PM – 4:30 PM US Central Time
McCormick Place Chicago


This course is an introduction to the skill set needed for troubleshooting LC-MS/MS-based laboratory developed tests (LDTs) and production batches. The course incorporates lectures and case history discussion in break out groups. Details of sample preparation flaws, common LC method errors and MS/MS detection pitfalls will be presented and basics of LC and MS/MS theory as they apply to method development will be reviewed as needed. Further, the interpretation of chromatograms, LC pressure traces and system suitability tests will be discussed. Examples will be shown of maintenance calendar annotation, service reports, batch documentation and longitudinal chromatogram overlays (within batch and between day) as tools for pinpointing method and process weak points. In breakout sessions, attendees will discuss a case history of instrument or reporting failures sourced to suboptimal LC-MS/MS method design/implementation.

Target Audience

This activity is designed for lab supervisors, lab directors (and/or assistant directors),medical technologists, toxicologists, and in-training individuals.

Prerequisite Knowledge 

Previous exposure to clinical LC-MS/MS testing and an understanding of the principles of sample preparation, liquid chromatography and tandem mass spectrometry.

What to Bring


Learning Objectives

  • List and define alternatives for common design flaws of sample preparation, LC and MS/MS aspects of clinical laboratory developed LC-MS/MS methods.
  • Describe examples of how system suitability test results, review of maintenance calendar annotation, and LC-MS/MS longitudinal chromatogram review revealed a weakness of LC-MS/MS method design or implementation.


Deborah French, PhD, DABCC, FADLM | University of California, San Francisco

Grace van der Gugten, BS | Alberta Precision Labs

Course Outline

  1. Can the Design of an MS/MS Detection Method Add Robustness? (60 mins.)
    Lecture followed by case study review in breakout groups.

  2. Building Robustness Into LC Methods (60 mins.)
    Lecture followed by case study review in breakout groups.

  3. Building Robustness Into Sample Preparation (60 mins.) 
    Lecture followed by case study review in breakout groups.