Academy · Intermediate

Understanding HPLC Testing

How HPLC quantifies peptide purity: column chemistry, gradient methods, detection wavelengths, and how to read the resulting chromatogram.

Principle of separation

HPLC pushes a mobile phase through a packed column. Compounds in the sample interact differently with the stationary phase and so elute at different times. UV-Vis detection (usually 214 nm for peptide bonds) records each compound as a peak.

Method choices that matter

Reverse-phase C18 with a water/acetonitrile gradient is standard for peptide purity. Method validation parameters — column temperature, flow rate, injection volume — should be documented on the COA.

Reading a chromatogram

One dominant peak with minor shoulders is normal. Purity is the main peak area as a percentage of total area. Watch for unresolved shoulders that could indicate a deletion sequence or oxidation product.

Frequently asked questions

What wavelength do you trust?+

214 nm for general peptide bond detection; 280 nm if the sequence contains tryptophan or tyrosine.

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