Quality

Net peptide content vs. purity

A peptide can test 99 percent pure by HPLC and still be only 80 percent peptide by weight. Purity and net peptide content measure different things, and an accurate research concentration depends on both.

Two numbers, two questions

HPLC purity asks how much of the peptide material is the right peptide. The sample runs through a reversed-phase column, the detector reads UV absorbance (usually at 214 to 220 nm, where the peptide bond absorbs), and purity is the main peak's share of the peptide signal. Truncated, deleted or oxidized sequences show up as the other peaks.

Net peptide content asks how much of the powder in the vial is peptide at all. A lyophilized peptide also contains counter-ions and bound water, and neither appears as a peptide peak, so purity cannot see them. Net peptide content is the peptide's share of the total weight, and it commonly falls somewhere between 60 and 90 percent.

Neither number replaces the other. The guide to reading a peptide COA covers where each appears on a certificate.

Where the rest of the weight comes from

Most synthetic peptides are purified by reversed-phase HPLC with trifluoroacetic acid (TFA) in the mobile phase. When the purified fractions are freeze-dried, each positively charged site on the peptide keeps a trifluoroacetate counter-ion, so the product is a TFA salt. The charged sites are the free N-terminal amine and the side chains of lysine (K), arginine (R) and histidine (H).

A TFA salt can be exchanged for acetate or hydrochloride (HCl). The counter-ion is lighter, but it is still there. On top of the salt, lyophilized peptides are hygroscopic and hold some water even when they look perfectly dry.

The result: the more basic residues a sequence has, and the shorter it is, the larger the share of the powder that is not peptide.

Theoretical peptide share by salt form

The table assumes one counter-ion on each basic site and no water at all, so it is an upper bound. Real net peptide content is lower once bound water is counted. The formula is peptide share = M / (M + n × m), where M is the peptide's average mass, n the number of basic sites and m the counter-ion's mass: 114.02 for TFA, 60.05 for acetic acid and 36.46 for HCl.

PeptideBasic sitesMass (Da)TFA saltAcetate saltHCl salt
BPC-15721,419.586.2%92.2%95.1%
Epitalon1390.377.4%86.7%91.5%
KPV2342.460.0%74.0%82.4%
Selank3751.968.7%80.7%87.3%
Semax2813.978.1%87.1%91.8%
DSIP1848.888.2%93.4%95.9%
Cartalax1333.374.5%84.7%90.1%
Thymosin Alpha-143,108.387.2%92.8%95.5%
Oxytocin11,007.289.8%94.4%96.5%
Kisspeptin-1021,302.485.1%91.6%94.7%
Sermorelin63,357.983.1%90.3%93.9%
AOD-960431,815.184.1%91.0%94.3%
MOTS-c52,174.679.2%87.9%92.3%
VIP73,325.880.6%88.8%92.9%
LL-37124,493.376.7%86.2%91.1%

BPC-157 shows how it works: mass 1,419.5, two basic sites (the N-terminus and one lysine), so as a TFA salt the peptide can be at most 1,419.5 / (1,419.5 + 2 × 114.02) = 86.2 percent of the powder. Short, basic sequences such as KPV lose far more of their weight to the salt.

How net peptide content is measured

  • Amino acid analysis (AAA): the peptide is hydrolyzed into its amino acids, which are quantified and compared with the weighed sample. It is the reference method.
  • Elemental (CHN) nitrogen analysis: measured nitrogen is compared with the nitrogen the sequence should contain.
  • UV absorbance at 280 nm: for sequences containing tryptophan or tyrosine, with the extinction coefficient converting absorbance to concentration.
  • Counter-ion assays: ion chromatography or fluorine-19 NMR measure TFA directly, which shows how much of the weight is salt.

TFA, acetate or HCl: does the salt form matter?

For most analytical work a TFA salt is fine, and it is the default because it comes straight out of purification. Residual TFA has been reported to affect some cell-based assays, and it lowers the pH of unbuffered solutions. Where that matters, labs specify acetate or HCl salt, which costs an extra exchange step and some yield.

Whatever the form, record it. Two lots of the same sequence in different salt forms are not interchangeable by weight.

Correcting a concentration for net content

Peptide mass = powder mass × net peptide content. Ten milligrams of powder at 80 percent net content holds 8 mg of peptide. To reach a target molar concentration, work out the peptide mass needed, then divide by the net content to get the powder to weigh.

Example: 100 µM of BPC-157 in 10 mL needs 1.4195 mg of peptide. At 80 percent net content, weigh 1.7744 mg of powder. The peptide molarity calculator takes the net content as an input and does this step for you.

What to ask a supplier

  • Is the labeled vial weight the powder weight or the peptide weight?
  • Which salt form is the lot: TFA, acetate or HCl?
  • Is net peptide content reported, and by which method?
  • Does the COA show HPLC purity and mass-spec identity for the lot you receive?

B2B Kits tests every lot for HPLC purity and mass-spec identity at an independent laboratory, and the lot COA is packed in every kit. See Testing & COAs.

Questions

What is net peptide content?

The peptide's share of the total powder weight in a vial. The rest is counter-ions left from purification, such as TFA or acetate, and bound water. It commonly falls between 60 and 90 percent.

Is net peptide content the same as purity?

No. HPLC purity is the main peak's share of the peptide signal, so it measures how much of the peptide material is the correct sequence. Net peptide content measures how much of the powder is peptide at all.

What is a TFA salt peptide?

A peptide whose positively charged sites (the free N-terminus, lysine, arginine and histidine) carry trifluoroacetate counter-ions, left over from HPLC purification with trifluoroacetic acid. TFA salts can be exchanged for acetate or HCl.

How do I calculate concentration with net peptide content?

Multiply the powder weight by the net peptide content to get the peptide weight, then calculate the concentration from the peptide weight. To hit a target concentration, divide the peptide mass you need by the net content to get the powder mass to weigh.

Why do short peptides have lower net peptide content?

Each basic site carries a counter-ion of fixed mass. In a short sequence those counter-ions are a larger share of the total weight, so less of the powder is peptide.