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Reverse-phase HPLC (revision 5)

Old revision·17:42, 6 Aug 2024·FormularyFrida

This is an old revision of this page, as it stood at 17:42, 6 Aug 2024, saved by FormularyFrida with the summary state the column chemistry and the gradient the figure was obtained on. It may differ substantially from the current revision, and any error it contains may since have been corrected.
Reverse-phase HPLC
AbbreviationRP-HPLC
Stationary phaseAlkyl chains bonded to silica, usually C18
Mobile phaseWater and acetonitrile with an acidic modifier
DetectionUV at 214 nm; sometimes 280 nm
Analytical method infobox · conventions

Reverse-phase HPLC is the mode of liquid chromatography in which the stationary phase is non-polar and the mobile phase is polar — the reverse of the normal-phase arrangement from which the name derives. It is the dominant analytical technique for peptides and the source of almost every purity figure on a peptide certificate.[1]

Separation follows hydrophobicity. A peptide adsorbs to the alkyl stationary phase from a largely aqueous mobile phase and desorbs as the organic proportion rises; the organic content at which it desorbs is characteristic and reproducible under fixed conditions.[2]

Conditions and what they control

[edit]
ParameterTypical valueWhat it changes
Column chemistryC18, sometimes C8 or C4Retention strength; C4 for large or very hydrophobic peptides
Particle size1.7–5 μmEfficiency and back-pressure
Modifier0.1% trifluoroacetic acidPeak shape; ion pairing
Gradient5–60% acetonitrileElution window and resolution
Gradient duration15–60 minResolution of close-eluting species
Temperature25–60 °CSelectivity, peak shape, viscosity
Detection214 nmSensitivity to the peptide bond

Gradient duration is the parameter with the largest effect on a reported purity figure. A shallow gradient run over an hour resolves species a fifteen-minute gradient merges, and the merged determination returns a higher number on identical material. Neither is wrong; they are different measurements. See Purity claim inflation.[2]

References

  1. ^ United States Pharmacopeia, General Chapter <621>, Chromatography.
  2. ^ a b Mant CT, Hodges RS. "Analysis of peptides by high-performance liquid chromatography." Methods in Enzymology 271:3–50 (1996). PMID 8782429.