How to Read a Chemical Reagent Certificate of Analysis (CoA)

A certificate of analysis is not a guarantee of quality. It is a record of the measurements someone chose to perform, and what it leaves out says as much as the numbers it reports. In practice, knowing how to read such a document comes down to one habit: checking which questions were answered before looking at the answers.

Below, we take such a document apart. We cover what it must contain to mean anything, which fields are most often left blank and why those ones in particular, how an ordinary certificate differs from a certified reference material, and where the limit lies on what the document can attest to at all.

Four things without which the document is decoration

Batch identification. A certificate describes a specific batch of material, not the substance in general. Without a batch number, there is no way to link the document to the container on the shelf, and that link is the only thing that gives it meaning. A document without a batch number describes something that cannot be identified.

The method name next to every result. “Purity: 99.2%” with no method stated is a number without a conceptual unit. A chromatographic assay, a mass balance, and quantitative nuclear magnetic resonance answer different questions and regularly give different values for the same sample. This is why combining several independent techniques is standard practice in the certification of reference materials.¹²

The date the analyses were performed. This means the measurement date, not the date the document was printed. For materials sensitive to moisture, light, or oxygen, the difference between a measurement taken a month ago and one taken three years ago can be larger than the difference between two batches.

Who performed the analysis. A manufacturer’s certificate, a certificate from an external laboratory, and a printout from an instrument are three different levels of credibility. None of them is disqualifying in itself, but it is worth knowing which one you are holding.

Fields that are most often blank

A missing field does not mean the analysis was not performed. It means the result was not reported, and for the recipient the effect is the same. Three items disappear from certificates most often, and all three can change how the purity result should be interpreted.

• Water content. A hygroscopic material can take up a percent of its mass from the air within hours. Chromatographic purity will not detect this, because water does not produce a peak under typical assay conditions. A mass balance will detect it, provided water was determined at all.
• Residual solvents. Leftovers from crystallization or drying. They are usually easy to detect by headspace gas chromatography, but only if someone looked for them.
• Metals and sulfated ash. These matter wherever the material is intended for assays sensitive to metal ions. The methodology for preparing and using reference materials in inorganic analysis has, in fact, an extensive literature of its own.³

Note the asymmetry: the absence of these fields almost always works in the material’s favor. Undetermined water raises the apparent purity, undetermined residual solvents do not lower it, and undetermined metals do not spoil the picture. A document that omits precisely these items is not neutrally incomplete.

Certificate of analysis vs. certified reference material

These are two different things, and confusing them can be costly.

A certificate of analysis says: “we measured this and that, and here is what we got.” It is a record.

A certified reference material is a material whose assigned value was established by a metrological procedure, with a stated uncertainty and traceability to higher-order standards. Producing such a material is a separate undertaking, described step by step in the literature, from reference materials for potency assays,⁴ through plant-substance standards,⁵ to materials for volatile organic compounds⁶ and construction materials used in quality assurance.⁷ The general requirements for this class of materials, and the demand for them, have been discussed separately.⁸

The practical consequence: a certified reference material has its uncertainty stated numerically. An ordinary certificate of analysis usually does not, which means the result is given without any information on how much it could differ on repetition. For comparative measurements this is a fundamental difference: without an uncertainty, you cannot say whether two values actually differ.

How to read the result itself

A few habits that catch most problems without reaching for any instrument.

Compare the declared number with the specification. If the specification reads “≥98%” and the result is “98.1%”, the material meets the requirement with a margin of one tenth of a percentage point. That is useful information of a different kind than “99.8%”, even though both pass.

Check consistency between items. A chromatographic purity of 99.5% alongside a water content of 1.2% is an internally strained combination. Both numbers may be correct, but together they say that the analyses measured different quantities and do not add up to one hundred.

See whether identity was confirmed. An infrared spectrum, a mass spectrum, a melting point, or an NMR spectrum are items that answer a different question than purity: the question of what the main substance is. A certificate of purity alone takes identity as a given.

Pay attention to the precision of the reported value. A result given as “99%” and one given as “99.17%” are claims of different weight. A number carrying more significant figures than the method can support is often a sign that the result was copied from the instrument without thought.

What a certificate will not tell you

The document describes a sample taken from the batch at the time of analysis. It does not describe the container now sitting on the shelf, and it says nothing about what happened to the material after the measurement: transport, storage conditions, or how many times the container was opened in a humid room.

Nor will it tell you whether the sample was representative of the whole batch. For homogeneous materials this is usually not a problem; for mixtures, materials of varying particle size, or materials that may have segregated during transport, it very much can be. Metrology knows this problem as material homogeneity, and in the production of reference materials it is studied separately, precisely because it does not follow from anything else.⁹

And most importantly: a certificate does not replace your own verification of the material’s identity when the outcome of your work depends on that identity. The document is a statement by the party supplying the material. That does not make it unreliable; it makes it a statement rather than a measurement performed in-house.

Checklist

• batch number matching the container label,
• date the analyses were performed, not just the date of issue,
• method stated for every result,
• water content determined or explicitly declared as not tested,
• a separate item confirming the identity of the substance,
• uncertainty of the result, if the material is to be used for comparative measurements,
• precision of the reported values consistent with the capabilities of the method.

Where the purity figure itself comes from, and why two correct analyses can give different values, is covered in our article on what the number on a certificate actually means. We describe every reagent in our catalog with its CAS number and declared purity, and how to read that declaration is exactly the subject of both articles.

References

Each entry below was retrieved from the PubMed database via the E-utilities interface and is not reproduced from memory. The PMID numbers link to the source records.

1. Liu H, Cheow PS, Yong S et al. Determination of purity values of amino acid reference materials by mass balance method: an approach to the quantification of related structure impurities. Anal Bioanal Chem. 2020;412:8023-8037. PMID: 32914399. DOI: 10.1007/s00216-020-02936-7.
2. Shehata AB, Rizk MS, Rend EA. Certification of caffeine reference material purity by ultraviolet/visible spectrophotometry and high-performance liquid chromatography with diode-array detection as two independent analytical methods. J Food Drug Anal. 2016;24:703-715. PMID: 28911607. DOI: 10.1016/j.jfda.2016.06.009.
3. Dybczyński R. Preparation and use of reference materials for quality assurance in inorganic trace analysis. Food Addit Contam. 2002;19:928-38. PMID: 12443554. DOI: 10.1080/0265203021000011791.
4. Ajorio ACFB, Rhodes VP, Rodrigues AP et al. Establishment of certified reference material for the potency assay in yellow fever vaccine quality control, in accordance with International Standards Organization guidance. J Pharm Biomed Anal. 2023;230:115395. PMID: 37079931. DOI: 10.1016/j.jpba.2023.115395.
5. Gong N, Zhang B, Yang D et al. Development of new reference material neohesperidin for quality control of dietary supplements. J Sci Food Agric. 2015;95:1885-91. PMID: 25170574. DOI: 10.1002/jsfa.6893.
6. Neves LA, Almeida RR, Rego EP et al. Certified reference material of volatile organic compounds for environmental analysis: BTEX in methanol. Anal Bioanal Chem. 2015;407:3225-9. PMID: 25450051. DOI: 10.1007/s00216-014-8314-6.
7. Lee MJ, Lee SH, Jung Y. Development of concrete reference material for quality assurance/quality control of gamma radioactivity measurement for nuclear power plant decommissioning waste. J Environ Radioact. 2022;255:107031. PMID: 36191508. DOI: 10.1016/j.jenvrad.2022.107031.
8. Kiełbasa A, Gadzała-Kopciuch R, Buszewski B. Reference Materials: Significance, General Requirements, and Demand. Crit Rev Anal Chem. 2016;46:224-35. PMID: 26042643. DOI: 10.1080/10408347.2015.1045120.
9. Ricci M, de Boer J, Johansen JE et al. Stepping-up accurate quantification of chlorinated paraffins: Successful certification of the first matrix reference material. Anal Chim Acta. 2024;1315:342757. PMID: 38879205. DOI: 10.1016/j.aca.2024.342757.