Reading a Certificate of Analysis: A Patient's Guide to Third-Party Testing

A certificate of analysis — usually called a CoA — is a document that reports the results of laboratory testing on a pharmaceutical ingredient or finished product. If you've ever asked a compounding pharmacy for proof that your semaglutide is what the label says it is, this is the document they should hand you.

The problem is that CoAs are written for pharmacists and chemists, not patients. They're dense with abbreviations, reference standards, and acceptance criteria that assume you already know pharmaceutical testing terminology. This guide translates the key sections into plain language so you can evaluate what you're reading.

Who Issues the CoA

A CoA can come from two sources, and the distinction matters:

• Supplier CoA: Issued by the API manufacturer or distributor. This tells the pharmacy what the manufacturer claims about the raw material. It arrives with the shipment.
• Independent CoA: Issued by a third-party laboratory that tested the material or finished product independently. This is verification — someone other than the seller confirming the product's identity and quality.

Both have value, but an independent CoA from an accredited testing laboratory (look for ISO 17025 accreditation) provides a layer of verification that a supplier's self-reported results cannot. Some compounding pharmacies commission both supplier and independent testing. Others rely solely on the supplier's CoA. Asking which approach your pharmacy uses is a reasonable quality question.

The Key Sections of a CoA

Product Identification

This section should clearly state what was tested: the chemical name (semaglutide or semaglutide sodium), the lot number, the date of manufacture, and the quantity represented. The lot number should match the lot number on your vial label. If these don't match, the CoA may not apply to your specific prescription.

Appearance

A basic physical description — typically "white to off-white powder" for lyophilized semaglutide API, or "clear, colorless to slightly yellow solution" for pre-mixed formulations. This section confirms the material looked the way pharmaceutical-grade semaglutide should look. Discoloration, turbidity, or particulate matter would be flagged here.

Identity Test

This section confirms that the material is actually semaglutide, not something else. Common identity testing methods include:

• HPLC (High-Performance Liquid Chromatography): Compares the retention time of the sample against a semaglutide reference standard. If the peaks match, the material is confirmed as semaglutide.
• Mass Spectrometry: Measures the molecular weight of the peptide. Semaglutide has a precise molecular weight; the test confirms it matches.
• Infrared Spectroscopy: Produces a molecular "fingerprint" that's compared against a reference spectrum.

The result should say "Conforms" or "Passes" — anything else is a red flag.

Purity / Assay

This is arguably the most important number on the CoA. It tells you what percentage of the material is actually the active drug. For pharmaceutical-grade semaglutide API, expect purity above 95% — many high-quality suppliers report 97-99%.

Purity is typically measured by HPLC and reported as "area percent" — the fraction of the chromatogram's total area represented by the main semaglutide peak. The remainder consists of related impurities (see below).

Related Substances / Impurities

No synthetic peptide is 100% pure. The manufacturing process inevitably produces small amounts of related peptides — deletion sequences (where an amino acid was skipped), truncation products (where the chain was cut short), or racemized amino acids (where the stereochemistry flipped). These are reported individually and as a total.

Typical specifications require each individual impurity to be below 1-2% and total impurities below 3-5%. Impurity levels well above these thresholds suggest manufacturing problems.

Peptide Content / Net Peptide

This number accounts for non-peptide components of the powder — primarily moisture and counterions (like sodium, if the salt form is used). If the CoA reports a purity of 98% but a net peptide content of 85%, it means 15% of the powder's weight is water and salts, not active drug. This number is critical for accurate dosing calculations.

Residual Solvents

The synthesis process uses organic solvents that must be removed from the final product. Common residual solvents include DMF, acetonitrile, and TFA. The CoA should report levels below ICH Q3C guideline limits — typically measured in parts per million (ppm).

Bacterial Endotoxins

For API intended for injectable preparations, endotoxin testing (using the LAL test) confirms the material is free of pyrogen-inducing bacterial fragments. The result is reported in Endotoxin Units per milligram (EU/mg), and should fall below the specification limit — typically less than 5 EU/mg for peptide API.

Sterility (Finished Product CoAs Only)

If the CoA covers a finished compounded product (not just the raw API), it should include sterility testing results confirming no microbial growth was detected. This is tested per USP <71> methodology, using a specified incubation period (typically 14 days).

Red Flags on a CoA

• Missing lot number or lot number that doesn't match your product
• No testing laboratory identified, or testing performed by the manufacturer only
• Purity below 95% without explanation
• Missing identity test (HPLC or MS confirmation)
• No endotoxin testing on injectable API
• "Not tested" appearing in multiple sections
• Specifications listed but no actual results reported
• Date of testing significantly older than the product's manufacture date

Providers With Documented Quality Programs

The Bottom Line

A CoA is not a guarantee of quality — it's a document that can be read, verified, and questioned. But a pharmacy that routinely provides CoAs for its compounded products, sources API from identifiable FDA-registered manufacturers, and can walk you through what the results mean is operating at a level of transparency that protects you. One that cannot or will not provide this documentation is asking you to trust without evidence — and that's a different proposition entirely.