Table 3 Overview of liquid-based separation technologies for NTS: substance domains, advantages and potential disadvantages

RPLC

Polar to non-polar

Straightforward, rather easy to understand separation

(very) hydrophilic compounds not retained

Injection solvent mismatch

MM–RPLC

Polar ionic to non-polar compounds

Expanding the RP compound domain towards ions

Neutral hydrophilic compounds not be well-retained

More complex optimisation

MM–HILIC

Very polar/hydrophilic and ionic

Complementary to RPLC

Hydrophobic compounds not retained

More complex optimisation

Solvent exchange required for aqueous samples

HILIC

Very polar/hydrophilic

Complementary to RPLC

Solvent exchange required for aqueous samples

Hydrophobic compounds not retained

IC

Large range of ions, incl. inorganics

Broad domain of ionic compounds

Only for ionic compounds

Removal of high salt load from eluents or samples necessary

Capillary electrophoresis

Large range of ions, incl. inorganics

Broad domain of ionic compounds

Only for ionic compounds

Low flow rates/injection volumes

Often lower sensitivity as compared to LC

SFC

Very hydrophilic to non-polar compounds

Green: less organic solvent consumption

Likely rather versatile tuning of method possible

Additional hardware required

Solvent exchange required for aqueous samples

Elution not yet very predictable

LCxLC

Depending on combination of columns

Combination of different separation strategies

Very high peak capacity and selectivity

Additional hardware required

Data size and high complexity for evaluation