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.
| Peptide | Basic sites | Mass (Da) | TFA salt | Acetate salt | HCl salt |
|---|---|---|---|---|---|
| BPC-157 | 2 | 1,419.5 | 86.2% | 92.2% | 95.1% |
| Epitalon | 1 | 390.3 | 77.4% | 86.7% | 91.5% |
| KPV | 2 | 342.4 | 60.0% | 74.0% | 82.4% |
| Selank | 3 | 751.9 | 68.7% | 80.7% | 87.3% |
| Semax | 2 | 813.9 | 78.1% | 87.1% | 91.8% |
| DSIP | 1 | 848.8 | 88.2% | 93.4% | 95.9% |
| Cartalax | 1 | 333.3 | 74.5% | 84.7% | 90.1% |
| Thymosin Alpha-1 | 4 | 3,108.3 | 87.2% | 92.8% | 95.5% |
| Oxytocin | 1 | 1,007.2 | 89.8% | 94.4% | 96.5% |
| Kisspeptin-10 | 2 | 1,302.4 | 85.1% | 91.6% | 94.7% |
| Sermorelin | 6 | 3,357.9 | 83.1% | 90.3% | 93.9% |
| AOD-9604 | 3 | 1,815.1 | 84.1% | 91.0% | 94.3% |
| MOTS-c | 5 | 2,174.6 | 79.2% | 87.9% | 92.3% |
| VIP | 7 | 3,325.8 | 80.6% | 88.8% | 92.9% |
| LL-37 | 12 | 4,493.3 | 76.7% | 86.2% | 91.1% |