Reference standards
A measured value is only as good as what it is measured against. A new compound has nothing to be measured against, so we establish its structure and content with independent methods first.
Purity is relative, content needs a reference
Purity needs no standard: it is the main peak against all peaks. Content does: the sample is compared against a reference standard of known content. For a novel compound, no characterised standard exists.
When the reference is missing, or wrong
| Situation | What goes wrong | What we do instead |
|---|---|---|
| No reference standard exists | The laboratory can only report relative purity. How much compound is in the powder stays unknown. | Measure content directly by qNMR, against a certified calibrant that is a different compound. |
| A reference of unknown quality, often another vendor’s batch | Every result inherits its error. The market ends up checking itself against itself. | Ask what the standard is and how it was characterised. Do not accept a content value measured against an uncharacterised standard. |
| The wrong reference: a different compound, isomer or salt form | A match confirms the wrong molecule. A wrong compound can still be 99% pure. | Confirm structure from first principles with accurate mass and NMR, and verify the building block before synthesis. |
| A market HPLC result of 99% or more | Water, counter-ions and residual solvents do not appear in the UV trace, so the figure says nothing about content. | Measure each one: water by Karl Fischer, counter-ions by ion chromatography, solvents by gas chromatography. Cross-check the total against qNMR. |
Two methods must agree
The rule we work to: two independent methods must agree, qNMR on one side and the sum of the measured impurities on the other. When they do, that batch becomes our own characterised reference for the compound, and later batches can be checked against it by routine HPLC.
For a novel compound, building that first reference is the real work.
Sources
- Bruker: Validation and implementation of qNMR for oligonucleotides and peptides: qNMR for content, compared with nitrogen, elemental and amino acid analysis
- Bachem: Quality control of amino acids and peptides: water, counter-ions and residual solvents
Questions about a compound?
Whether you need a niche compound sourced or a private synthesis organised, or want to work with us as a supplier or laboratory, tell us what you are working on.
Talk to us