Only One of These Three Words Is a Specification

Of the three terms “crude”, “desalted” and “>95%”, exactly one states a purity. The other two report what was done, or left undone, to a batch of material. Treating all three as marks on one continuous scale is the misconception that causes more confusion about peptide supply than anything else.

Two process words and one number

The mixture that leaves the support

Synthesis ends with a cleavage that simultaneously frees the peptide from its support and removes the protecting groups. What lands in the flask is a population, not a compound: target sequence, deletion and truncation sequences from every coupling that came up short, species still partly protected, oxidation products, scavengers together with their adducts, and the acid used for cleavage.

What proportion of that population is target depends overwhelmingly on chain length. Assemble something short and well behaved and it can arrive at 70–90%. Something long or awkward may arrive under 50%. The underlying arithmetic appears in the solid-phase synthesis cycle.

Why the final few percent costs so much

Grades on offer are usually >95% and >98%, sometimes >99%, and each step upward costs out of proportion to the gain. The reason is structural. Whatever is hardest to remove is whatever sits nearest the target in the separation, a lone deletion, an oxidation, an isomer, so reaching the last stretch demands a far shallower gradient, a second purification on an orthogonal basis, or simply tolerating much less product at the end.

Which points at the real economics. Purification discards material. Fractions taken from the flanks of a peak carry target mingled with whatever elutes closest, so collecting them buys yield at the expense of purity, and tightening the collection window trades the other way. A >98% preparation is consequently not a >95% preparation with one more operation bolted on; more often it is a preparation in which a considerably greater share of everything synthesized went into the waste. Instrument time is not the dominant difference between the grades. Discarded material is.

A percentage with no method attached

Any grade of >95% means 95% according to some measurement, and every such measurement has a column, a gradient, a wavelength and a run length behind it. One material can therefore carry different numbers under different methods without anybody being mistaken, for reasons developed in what “98% by HPLC” is a percentage of and why certificates disagree on purity. Quote a grade with no method behind it and you have made a claim about a number rather than reported a measurement.

Blind spots shared by all three

Every one of these terms concerns chromatographic purity, meaning the share of eluting, absorbing material that happens to be the target. Several things fall outside that entirely. Net peptide content does: how much of the weighed solid is actually peptide rather than counter-ion and water is a separate question, and something 98% pure can be 75% peptide by mass. Stereochemistry does too, since swapping a D residue for an L one escapes both the separation and the mass. Anything concealed beneath the main peak is counted as main peak, co-elution being invisible by definition. Elemental impurities, residual solvents and endotoxin sit outside the measurement altogether.

Picking a grade without overpaying

Match the grade to what the planned measurement actually demands, since higher is not reliably better value. Compare a material structurally or analytically against a reference standard and high purity earns its price, because impurities interfere with the comparison directly. Develop a method, or use the peptide as a reagent rather than as the object of study, and crude or desalted material frequently does the job for a fraction of the outlay.

Whichever you choose, the documentation should say plainly which of the three it describes, and where it describes the third, it should report the measured value together with the method that produced it.