Several liquid chromatography (LC) troubleshooting topics never get old because there are some problems that persist in the practice of LC, even as instrument technology improves over time. There are many ways for things to go wrong in an LC system that ultimately manifest as deviations from expected retention times. Developing a short list of the likely causes of these deviations can help streamline our troubleshooting experience when retention-related problems occur.

Writing this “LC Troubleshooting” column and thinking about topics each month is interesting in the sense that there are some topics that never get old. Although certain topics or ideas become obsolete once they are displaced by newer and better ideas in the chromatography research world, there are certain topics in the troubleshooting world that have remained relevant since the first troubleshooting article appeared in this magazine (LC Magazine at that time) in 1983 (1). Over the last few years, I’ve focused several “LC Troubleshooting” installments on contemporary trends (the relatively recent advances in our understanding of the effects of pressure on retention [2]) in liquid chromatography (LC) that are affecting the way we approach our interpretation of LC results and approach troubleshooting with modern LC instruments. In this installment, I am continuing a series I started in December of 2021 (3) that focuses on some of the “bread and butter” topics of LC troubleshooting—those elements that are essential for any troubleshooter, no matter the vintage of the system we are working with. The topics at the heart of this series are highly related to the well-known “LC Troubleshooting” wall chart (4) that hangs in many laboratories. For the second installment in this series, I focus on problems related to retention (too low, too high, and changing unexpectedly) in reversed-phase (RP) LC separations. I hope LC users young and old will find some useful tips and reminders related to this important topic.

Pressure Problems

Essentials of LC Troubleshooting, Part I: Pressure Problems
December 1, 2021
Dwight R. Stoll
LCGC North America, December 2021, Volume 39, Issue 12
Pages: 572–574

Misbehaving Retention Times

Essentials of LC Troubleshooting, Part II: Misbehaving Retention Times
April 1, 2022
Dwight R. Stoll
LCGC North America, April 2022, Volume 40, Issue 4
Pages: 151–155

Those Peaks Don’t Look Right

Essentials of LC Troubleshooting, Part 3: Those Peaks Don’t Look Right
September 1, 2022
Dwight R. Stoll
LCGC Europe, September 2022, Volume 35, Issue 08
Pages: 325 – 329

What Is Going On with the Baseline?

Essentials of LC Troubleshooting, Part IV: What Is Going On with the Baseline?
August 1, 2022
Dwight R. Stoll
LCGC North America, August 2022, Volume 40, Issue 8
Pages: 338–342
https://doi.org/10.56530/lcgc.na.tk9778b8

What Happened to My Sensitivity?

Essentials of LC Troubleshooting, Part V: What Happened to My Sensitivity?
October 1, 2022
Dwight R. Stoll
LCGC North America, October 2022, Volume 40, Issue 10
Pages: 471–475,483
https://doi.org/10.56530/lcgc.na.uk2876b9

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Sources #

1: Essentials of LC Troubleshooting, Part I: Pressure Problems
2: Essentials of LC Troubleshooting, Part II: Misbehaving Retention Times
3: Essentials of LC Troubleshooting, Part III: Those Peaks Don’t Look Right
4: Essentials of LC Troubleshooting, Part IV: What Is Going On with the Baseline?
5: Essentials of LC Troubleshooting, Part V: What Happened to My Sensitivity?