Two ways to work: Find equivalents & orthogonals — pick a reference column and instantly rank its swap-ready backups (Fs ≤ 3) and its most orthogonal columns (Fs ≥ 10) across all 817 columns; or Compare selected columns — put your column head-to-head against a shortlist you choose, with the Factor of Similarity and the per-term differences that explain why they diverge. Powered by the Hydrophobic-Subtraction Model across 817 real, published columns.
Two reversed-phase columns with the same nominal chemistry (say, "C18") can give very different separations. The published Hydrophobic-Subtraction Model (HSM) explains why by describing each column with five interaction terms, so columns can be compared objectively rather than by trade name.
Retention on a column, relative to a reference, is modelled as the sum of five contributions:
log(k / kref) = η'H − σ'S* + β'A + α'B + κ'C| Term | Column property |
|---|---|
| H | Hydrophobicity |
| S* | Steric resistance to bulky solutes |
| A | Hydrogen-bond acidity (silanol activity) |
| B | Hydrogen-bond basicity |
| C | Cation-exchange / ionic interaction (pH-dependent) |
Two columns are considered near-equivalent when the differences in these terms are small — expressed as a single column-comparison distance (often written Fs), where a low value means the columns should give similar selectivity.
Two C18 phases have nearly identical H (hydrophobicity) but very different C (ionic) terms. For neutral analytes they behave alike, but for a basic, ionisable analyte the difference in C produces a large selectivity gap — so they are not interchangeable in a method that separates ionisable compounds.
Reference: Snyder, Dolan & Carr, J. Chromatogr. A 1060 (2004) 77; USP <621> column-equivalence principles.
Small differences across all five HSM terms — a low overall comparison distance. Equivalence is also analyte-dependent: columns that match for neutrals may diverge sharply for acids or bases because of the C (ionic) term.
A close HSM match is a strong starting point and is widely used to shortlist alternatives, but any substitution in a validated method still requires experimental verification and appropriate change control.
The C (ionic) interaction depends on whether analyte and silanols are charged, which pH controls. Two columns can look equivalent at one pH and very different at another.