Best of the Week: Slalom Chromatography, LC–MS Strategies for Oligonucleotide Analysis

ChromatographyOnline.com articles this week highlighted advances in analytical science, including slalom chromatography (SC) as a fast, high-resolution, and highly sensitive alternative to traditional DNA/RNA separation methods, along with its growing role in cell and gene therapy workflows. It also covered broader topics such as evolving analytical procedure lifecycle standards, liquid chromatography-mass spectrometry (LC–MS) strategies for oligonucleotide analysis, machine learning selection in analytical chemistry, and improved detection of toxic compounds using advanced ion mobility–MS techniques.

This is the Best of the Week.

Slalom Chromatography (Part 1): From Gels to Modern UHPLC Slalom Chromatography

Slalom Chromatography (Part 2): A Novel Technique to Separate Large Nucleic Acids

Part 1 of this series¹ reviews the history, renewed interest, and updated mechanism of slalom chromatography (SC), showing that it separates DNA/RNA via an out-of-equilibrium process driven by entropic elasticity and flow-induced forces, enabling faster and higher-resolution analysis than traditional methods like GPC, HDC, or agarose gel electrophoresis (AGE). Part 2² demonstrates SC’s practical advantages in cell and gene therapy workflows, highlighting its rapid, sensitive, and high-throughput performance—up to ~40× more sensitive than AGE—as a robust alternative for nucleic acid characterization in research, quality control, and therapeutic development.

Analytical Procedure Lifecycle Approaches in Accordance with ICH Q14 and ICH Q2(R2): Opportunity Knocks, or Just Another Challenge and Headache? Part 1

The first³ in a series of articles exploring the current analytical procedure lifecycle practices with multiple industrial and regulatory experts and consultants in the field, and addresses if this is a great opportunity to develop a greater understanding of method performance to ensure continuous improvement and regulatory flexibility, or if it is just additional challenges, complexity, and headaches.

Challenges and Solutions in Oligonucleotide Analysis, Part 3: LC–MS Methods

Dwight Stoll and Martin Gilar describe the utility of liquid chromatography coupled with mass spectrometric detection (LC–MS) for analysis of oligonucleotides (ONs), discuss recommended LC modes and mobile phases, and highlight challenges encountered in these applications, along with potential solutions.⁴

Choosing the Right ML Approach in Analytical Chemistry

Kevin Schug outlines the criteria used to select machine learning methods for analytical problems and how success is defined and evaluated.⁵

Determination of Pyrrolizidine Alkaloids in Food via LC-cIM-HRMS

A recent study shows that integrating multipass cyclic ion mobility spectrometry into liquid chromatography-high-resolution mass spectrometry improves detection and separation of toxic plant-derived pyrrolizidine alkaloids, including previously indistinguishable epimers, in complex food samples. LCGC International spoke to Laura Carbonell-Rozas, lead author of that paper, about the study.⁶

References

1. Gritti, F.; Valshnav, J.; Adepaali, B. et al. Slalom Chromatography (Part 1): From Gels to Modern UHPLC Slalom Chromatography. Chromatography Online website. https://www.chromatographyonline.com/view/slalom-chromatography-part-i-from-gels-to-modern-uhplc-slalom-chromatography (accessed 2026-04-10)
2. Gritti, F.; Valshnav, J.; Adepaali, B.; Gritti, F. et al. Slalom Chromatography (Part 2): A Novel Technique to Separate Large Nucleic Acids.Chromatography Online website. https://www.chromatographyonline.com/view/slalom-chromatography-part-2-a-novel-technique-to-separate-large-nucleic-acids (accessed 2026-04-10)
3. Mahr. A. G.; Roussel, J.-M.; Flores Ortiz, L. et al. Analytical Procedure Lifecycle Approaches in Accordance with ICH Q14 and ICH Q2(R2): Opportunity Knocks, or Just Another Challenge and Headache? Part 1. Chromatography Online website. https://www.chromatographyonline.com/view/analytical-procedure-lifecycle-approaches-in-accordance-with-ich-q14-and-ich-q2-r2-opportunity-knocks-or-just-another-challenge-and-headache-part-1 (accessed 2026-04-10)
4. Stoll, D. R.; Gilar, M. Challenges and Solutions in Oligonucleotide Analysis, Part 3: LC–MS Methods. Chromatography Online website.https://www.chromatographyonline.com/view/challenges-and-solutions-in-oligonucleotide-analysis-part-3-lc-ms-methods (accessed 2026-04-10)
5. Schug, K. A.; Jones, K. Choosing the Right ML Approach in Analytical Chemistry. Chromatography Online website. https://www.chromatographyonline.com/view/choosing-the-right-ml-approach-in-analytical-chemistry

(accessed 2026-04-10)
6. Carbonell-Rozas, L.; Chasse, J. Determination of Pyrrolizidine Alkaloids in Food via LC-cIM-HRMS. Chromatography Online website. https://www.chromatographyonline.com/view/determination-of-pyrrolizidine-alkaloids-in-food-via-lc-cim-hrms (accessed 2026-04-10)