UDCA Specification Guide: EP vs USP Limits & COA Checks
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Ursodeoxycholic acid specification is not one document — it is two different pharmacopoeial standards that differ in assay range, impurity limits, optical rotation, and test method. If you are quoted "Ursodiol, USP" and you release against Ph. Eur., three parameters will fail. This guide sets the two monographs side by side, explains the nine European related substances by name and letter, and gives a 20-minute checklist for reading a certificate of analysis.
It is published by JAN Bio, a customised supply-chain partner for bile-acid raw materials. We do not hold pharmacopoeial registrations, and we say so at the outset rather than let you discover it after a sample order. What we commit to instead is a complete and traceable document set, a 1 kg minimum order, a four-week turnaround, and batch-level traceability. Sections 7 and 8 explain what that means in practice.
1. Why "specification" means three different things in a purchase order
When a formulator asks for a specification, they usually mean one of three documents, and confusing them is the most common source of a rejected batch.
- Pharmacopoeial compliance — the substance meets the general monograph and the individual monograph for that pharmacopoeia. This is the baseline qualification.
- Batch release specification — the manufacturer's internal limits, which must be at least as tight as the monograph but are often tighter. This is what actually appears on a certificate of analysis.
- Regulatory dossier — the drug master file or certificate of suitability that supports a marketing authorisation. This is a filing commitment, not a test result.
A supplier can be fully compliant with the pharmacopoeia and still fail your internal specification, because your formulation may require tighter optical rotation or a lower lithocholic acid limit than the monograph demands. Always ask which document your quotation is based on.
The three layers come from different parties, and that is the practical point. A batch release specification is issued by whoever releases the batch. A regulatory dossier is a filing commitment held by whoever files it. When you are sourcing in small quantities, the useful question is not who holds a dossier, but who will hand you a complete and traceable document set for the quantity you actually need.
2. The two pharmacopoeias you will actually be quoted against
Ph. Eur. — Acidum ursodeoxycholicum
The European monograph defines ursodeoxycholic acid as a white or almost white powder, practically insoluble in water and freely soluble in ethanol (96 per cent). Identification is by infrared absorption, thin-layer chromatography, and a colour reaction. Assay is by titration and must fall between 99.0 and 101.0 per cent, calculated on the dried substance.
Related substances in the current European monograph are controlled by two different techniques. Lithocholic acid is limited separately by TLC to not more than 0.1 per cent. Chenodeoxycholic acid and the 3β,7β isomer are identified and controlled by an HPLC method with refractive index detection. The 2022 revision that moved chenodeoxycholic acid from TLC to HPLC-RI is the single most important change in this monograph in the last decade, and many supplier specifications still on the market have not caught up with it.
USP — Ursodiol
The United States Pharmacopeia uses the name Ursodiol. It is the same molecule (CAS 128-13-2, C24H40O4, MW 392.57), but the acceptance criteria are written differently. Assay is 98.5 to 101.5 per cent on the dried basis — a wider window than the European monograph. Melting range is 200 to 205 °C. Loss on drying is not more than 0.5 per cent after three hours at 105 °C, which is twice as strict as the European limit. Heavy metals are limited to 0.001 per cent, equivalent to 10 ppm, half the European limit of 20 ppm.
Related compounds in the USP monograph are still determined by TLC, with chenodiol limited to 1.5 per cent, lithocholic acid to 0.05 per cent, and any other impurity to 0.1 per cent.
3. Side-by-side acceptance criteria
| Parameter | Ph. Eur. (Acidum ursodeoxycholicum) | USP (Ursodiol) | Which is tighter |
|---|---|---|---|
| Assay (dried basis) | 99.0 – 101.0 % | 98.5 – 101.5 % | Ph. Eur. |
| Specific optical rotation | +58.0° to +62.0° | +57° to +62° | Ph. Eur. (at the low end) |
| Melting range | About 202 °C | 200 – 205 °C | Different basis |
| Loss on drying | ≤ 1.0 % (105 °C) | ≤ 0.5 % (105 °C, 3 h) | USP |
| Sulphated ash / residue on ignition | ≤ 0.1 % | ≤ 0.1 % | Equal |
| Heavy metals | ≤ 20 ppm | ≤ 10 ppm (0.001 %) | USP |
| Chenodeoxycholic acid | ≤ 1.0 % (HPLC-RI) | ≤ 1.5 % (TLC) | Ph. Eur. |
| Lithocholic acid | ≤ 0.1 % (TLC, separate test) | ≤ 0.05 % (TLC) | USP |
| Any other individual impurity | ≤ 0.25 % (TLC) | ≤ 0.1 % (TLC) | USP |
| Residual solvents | Ph. Eur. 5.4 / ICH Q3C | USP <467> / ICH Q3C | Equivalent |
Read this before you compare two quotations. A certificate stating "loss on drying 0.7 %" passes Ph. Eur. and fails USP. A certificate stating "lithocholic acid 0.08 %" passes Ph. Eur. and fails USP. Neither is a defect — but if your dossier was written against the wrong monograph, it becomes one after you have paid for the batch.
4. The nine European related substances, by letter and by name
The current European Pharmacopoeia lists nine potential related substances for ursodeoxycholic acid, designated impurity A through I. Most certificates of analysis name them by chemical name; most audit questionnaires ask about them by letter. You need both to read a COA critically.
| Impurity | Ph. Eur. name | Common name / abbreviation | Note |
|---|---|---|---|
| A | Chenodeoxycholic acid | CDCA | Principal process-related impurity; also a starting material in most synthetic routes |
| B | Cholic acid | CA | Trihydroxy analogue |
| C | Lithocholic acid | LCA | Monographed separately; toxic in small quantities. Usually the parameter QC teams watch hardest |
| D | 3α,7α-dihydroxy-5β-cholan-24-oic acid positional isomer | — | Isomeric; difficult to separate |
| E | Deoxycholic acid | DCA | Reported as toxic at low levels; a key impurity to interrogate on the COA |
| F | 7-Ketolithocholic acid | 7-KLCA | Also sold as a synthesis intermediate in its own right; frequently omitted from COAs that only report A, B, C and E |
| G | Methyl ursodeoxycholate | Methyl ester | Process ester; relevant for ester-based routes |
| H | 3β,7β-dihydroxy-5β-cholan-24-oic acid | 3β,7β isomer | Controlled by HPLC-RI alongside impurity A in the current monograph |
| I | 5β-Cholane-3α,7β,24-triol | — | Alcohol analogue |
Two practical consequences follow. First, a COA that reports only "related substances: complies" tells you nothing — you need the numeric result for lithocholic acid at minimum, and preferably for chenodeoxycholic acid and each unspecified impurity. Second, the pharmacopoeial methods cannot quantify all nine impurities simultaneously; the monograph controls several of them only through the general monograph thresholds for reporting, identification, and qualification. If your application needs a full impurity profile across all nine, that is a method-development conversation with your supplier, not a specification sheet request.
5. Three numbers buyers misread most often
Specific optical rotation
This is the single parameter that most reliably distinguishes genuine ursodeoxycholic acid from a mis-labelled batch, because the 3β,7β isomer and chenodeoxycholic acid both shift the reading. The European range starts at +58.0°, the USP range at +57°. A batch reading +57.5° passes USP and fails Ph. Eur. Confirm which range your dossier cites before accepting a certificate.
Lithocholic acid
Frequently the most consequential impurity and the one most often reported as "not detected" without a limit of detection being stated. Always ask for the LOD and LOQ alongside the result. A "not detected" against an LOQ of 0.02 per cent is meaningful; a "not detected" with no method information is not.
Loss on drying
Ursodeoxycholic acid is not markedly hygroscopic, but packaging and storage climate change the reading. The USP limit of 0.5 per cent leaves very little margin for a shipment that has been opened, sampled, and re-closed in a humid climate. If your specification cites USP, verify that the packaging is moisture-barrier foil and not a simple liner.
6. A 20-minute COA verification checklist
Run these eight checks before you move a certificate into your supplier qualification file.
- Monograph citation. Does the COA state "Ph. Eur." or "USP" explicitly, with the edition or year? "BP/EP/USP compliant" on a single line is not a citation.
- Assay range matches the cited monograph. 99.0–101.0 % implies Ph. Eur. 98.5–101.5 % implies USP. A certificate showing 98.8 % against a claim of Ph. Eur. compliance is out of specification.
- Numeric result for lithocholic acid. Not a tick, not "complies" — a number with a limit.
- Numeric results for chenodeoxycholic acid and total unspecified impurities.
- Optical rotation with the stated solvent and concentration. Ph. Eur. specifies anhydrous ethanol; concentration and temperature must be recorded.
- Heavy metals with the method reference. Limit test C at 20 ppm under Ph. Eur., or 0.001 per cent under USP.
- Residual solvents against ICH Q3C. Class 2 solvents require a numeric result, not a statement of compliance.
- Batch number, manufacture date, retest or expiry date, and the signature of the QC releasing officer. A COA without a batch linkage cannot be used in a qualification file.
If you already hold a certificate and want a second read on it, send it to us with the monograph you are releasing against. We will work through this list and tell you what is missing, whether or not you order from us.
7. What we can and cannot put in a document package
The documents that surround a batch come from different parties. The two tables below separate what we supply from what we do not hold.
Table 1 — Supplied by JAN Bio
| Document | Provided | Issued by |
|---|---|---|
| Certificate of analysis for the specific batch, with numeric impurity results | With every batch | Releasing laboratory of the manufacturing site |
| Batch number, manufacture date, retest date, batch traceability record | With every batch | Manufacturing site and JAN Bio |
| Material safety data sheet in the language of the destination market | On request | Manufacturing site |
| ICH Q3C residual solvent statement, with numeric results where a Class 2 solvent is used | On request | Manufacturing site |
| ICH Q3D elemental impurity risk assessment | On request | Manufacturing site |
| TSE/BSE statement, or a declaration that the material is of synthetic origin | On request | Manufacturing site |
| Stability data supporting the proposed retest period | On request | Manufacturing site |
Table 2 — Not held by JAN Bio
| Document | Status | Held / filed by |
|---|---|---|
| Site GMP certificate of the manufacturing site | Not held by JAN Bio | Manufacturing site (to verify, contact the site directly) |
| Certificate of suitability to the European Pharmacopoeia (CEP) | Not held by JAN Bio | Filed by a registration holder, not by us |
| Drug master file (DMF), or DMF reference letter | Not held by JAN Bio | Filed by a registration holder, not by us |
The three documents in the second table are unavailable from us, and it is worth being direct about why. A site GMP certificate is held by the manufacturing site; a CEP and a DMF are filed by the party that takes regulatory responsibility for the substance in a given market. None of them are in our hands, and we will not imply otherwise. If your project cannot proceed without a CEP or a DMF reference letter, we are not the right supplier today — we would rather tell you that in the first email than after a sample order. If your qualification process requires only the batch-level documents in the first table, those are what we supply as standard, from 1 kg upward.
8. Where this guide comes from
JAN Bio (Shenzhen Jieanneng Technology Co., Ltd.) supplies bile-acid raw materials — ursodeoxycholic acid, chenodeoxycholic acid, 7-ketolithocholic acid and related intermediates — to research groups, supplement brands and speciality feed producers.
We are not a manufacturer. Production is carried out by our partner manufacturing sites. Our function is the layer between the production record and your incoming goods release: document control, batch traceability, small-quantity supply, and the technical correspondence around an order. Four commitments define that layer — a complete and traceable document set with every batch, a 1 kg minimum order, a four-week turnaround quoted as a date rather than a range, and batch-level traceability from production record to the certificate you receive. An order a large manufacturer would decline as too small is not an exception we tolerate; it is the part of the market this company was built to serve.
Need the actual batch data? Request the certificate of analysis for the lot you are evaluating, or contact our technical team to discuss specification requirements for your market. Technical enquiries: sales@janbio.com.
Frequently asked questions
Is USP ursodiol the same as Ph. Eur. ursodeoxycholic acid?
Same molecule, different acceptance criteria. Assay ranges, optical rotation limits, loss on drying, heavy metals, and related-substance limits all differ, and the two monographs do not use the same test methods for related substances. A batch cannot be assumed compliant with both.
What is the difference between UDCA and ursodiol?
Ursodiol is the United States Pharmacopeia name for the same substance that the European Pharmacopoeia calls acidum ursodeoxycholicum, commonly abbreviated UDCA. CAS number 128-13-2 applies to both. Use the pharmacopoeial name of the destination market in your documentation.
What is impurity F in ursodeoxycholic acid?
Impurity F is 7-ketolithocholic acid, abbreviated 7-KLCA. It is both a potential process-related impurity in ursodeoxycholic acid and a commercial intermediate in its own right.
What is the limit for lithocholic acid in UDCA?
Not more than 0.1 per cent under Ph. Eur., tested separately by TLC, and not more than 0.05 per cent under USP by TLC. Lithocholic acid is reported to be toxic at low levels and is usually the impurity that triggers an out-of-specification investigation.
Which solvents are controlled in ursodeoxycholic acid?
Residual solvents are controlled against ICH Q3C. The solvents most commonly encountered in bile-acid processing are acetone, methanol, and secondary butyl alcohol, all Class 2 or Class 3 solvents requiring a numeric result where a Class 2 solvent is used.
Can a specification be met but the batch still be rejected?
Yes. Pharmacopoeial compliance is a minimum. If your formulation requires a tighter optical rotation window, a lower lithocholic acid limit, or a narrower particle-size distribution than the monograph specifies, a compliant batch can still fail your internal specification.
Is JAN Bio a manufacturer?
No. JAN Bio is a supply-chain partner for bile-acid raw materials, not a production site. Manufacture is carried out by partner facilities. What we hold is the commercial, documentation and traceability layer: batch-level records, certificate control, supply from 1 kg, and a four-week standard turnaround.
Summary
Ursodeoxycholic acid specification is a choice between two pharmacopoeial systems, not a single number. Confirm which monograph your dossier cites, check that every certificate names it explicitly, insist on numeric impurity results rather than compliance statements, and verify that your packaging protects the loss-on-drying margin your monograph allows. These four checks resolve the majority of specification disputes before they reach a rejected batch.
The fifth question is commercial, and it is the one most often left unasked. Once you know what the specification requires, the next questions are who will supply the quantity you need, with the document set you need, on a date they will commit to in writing. When that quantity is measured in kilograms rather than tonnes, the answer is rarely the manufacturer at the top of the industry league tables.
This guide describes pharmacopoeial acceptance criteria for ursodeoxycholic acid as a pharmaceutical substance. It is written for R&D, quality and sourcing professionals and is not intended for patients or as medical information. The values given are pharmacopoeial requirements and do not represent the release specification of any particular batch supplied by JAN Bio.