A CLN reader submitted the following liquid chromatography-tandem mass spectrometry (LC-MS/MS) troubleshooting case involving metadata: After an instrument preventative maintenance, the ion ratios for a cannabinoid metabolite assay began consistently failing the validated acceptance range. The service representative could not find anything wrong with the instrument. Close inspection of the chromatography identified a recent trend to an elevated and noisy baseline as a possible source of the ion ratio failures.

Although the LC column was well within its expected lifetime (for number of injections), a new column was installed, after which the baseline improved and ion ratios became acceptable. In addition to knowledgeable inspection of chromatographic changes over time, parameter/lot change tracking and graphing metadata such as ion ratios are useful troubleshooting tools (See figure below).

Graphing metadata such as ion ratios for troubleshooting

(This example of MRM (ion) ratio variance over time is courtesy of Heather Hochrein, CLS (ASCP), toxicology/mass spectrometry laboratory, Center for Advanced Laboratory Medicine, University of California San Diego Health System.)

The mundane recording of lot information, day after day, and the time-consuming review of multiple chromatograms may suddenly all seem worthwhile when it helps to solve the case.

We thank the CLN reader for sharing this troubleshooting example.

Related content: See articles from Kara Lynch, PhD and Adam Zabell, PhD, in the May issue of CLN’s Focus on Mass Spectrometry about LC-MS/MS quality assurance and metadata monitoring.