Albendazole is one of the few benzimidazole anthelmintics that is used at real scale in both human and veterinary medicine, and that dual use is why the same CAS number arrives with two quite different specifications. This guide covers the molecule, the two grade families, the impurity set that separates them, and the particle-size requirement that both share. It is the technical companion to the albendazole product page, which carries the full parameter tables.
Identity and physical properties
| Property | Value | Practical significance |
|---|---|---|
| Chemical name | Methyl [5-(propylthio)-1H-benzimidazol-2-yl]carbamate | The propylthio side chain is what distinguishes it from fenbendazole, which carries a phenylthio group instead |
| CAS | 54965-21-8 | – |
| Formula / molecular weight | C12H15N3O2S / 265.33 | – |
| Appearance | White to slightly yellowish powder | Yellowing is the first visible indicator of oxidative degradation |
| Aqueous solubility | Very low | The defining formulation problem – this is a BCS Class II molecule |
| Stability | Sensitive to oxidation and light | Drives the impurity limits and the packaging requirements |
| Particle size (supplied) | D90 max 20 micrometre | Micronisation is a specification requirement, not a marketing option |
How it works, and why the metabolite matters commercially
Benzimidazoles bind to parasite beta-tubulin with far higher affinity than to the mammalian protein, blocking microtubule polymerisation. The parasite loses its ability to take up glucose, glycogen stores deplete, and energy generation fails. Selectivity comes from the affinity difference, not from a unique target.
| Species | Role | Why it appears in the specification |
|---|---|---|
| Albendazole | The administered molecule | The assay measures this |
| Albendazole sulfoxide | The active metabolite, formed by hepatic CYP-mediated oxidation | It is also an oxidative degradation product, which is why “albendazole oxide” sits on the impurity list as well as in the pharmacology |
| Albendazole sulfone | Further oxidation product, essentially inactive | Controlled together with the sulfoxide at a combined 0.4% limit |
The consequence for a buyer: a lot that has oxidised in storage loses assay and gains sulfoxide and sulfone at the same time. The impurity limits and the assay are measuring the same process from two directions, which is why the sulfoxide/sulfone figure is worth watching across deliveries rather than only on the release certificate.
Manufacturing route in outline
Industrial albendazole is built on a benzimidazole ring closure: a substituted ortho-phenylenediamine is condensed with a carbamate-bearing reagent to close the imidazole ring, and the propylthio side chain is introduced through the aromatic substitution pattern. The purification and micronisation steps are what decide the impurity profile and the particle size, and they are where suppliers differentiate.
| Stage | What it controls | Which specification items it affects |
|---|---|---|
| Ring construction and side-chain installation | Regioisomer content and the related-compound profile | Albendazole related compounds A and F, fenbendazole related compounds A and B |
| Purification | Residual related substances and colour | Total impurities, unspecified impurity, appearance |
| Solvent handling and drying | Residual solvent levels | Methanol and toluene limits (human grade only) |
| Micronisation | Particle size distribution | D90 / 90% below 20 micrometre |
| Packing and storage control | Oxidation during hold | Albendazole oxide and sulfone, colour, assay |
The two grade families side by side
| Attribute | Human – USP | Human – EP 12.3 | Veterinary |
|---|---|---|---|
| Assay window | 98.0 – 102.0% (both sides) | Per monograph, on request | Min 98.5% (single-sided) |
| Named related compounds | Six, each with its own limit | EP impurity nomenclature, issued on request | None – total limit only |
| Total impurities | Max 0.8% | Per monograph | Max 1.0% |
| Unspecified impurity | Max 0.10% | Per monograph | Not separately limited |
| Genotoxic impurity (ethyl carbamate) | Max 0.15% if present | Per monograph | Not tested |
| Residual solvents | Methanol 3000 ppm, toluene 890 ppm | Per monograph | Not tested |
| Iron salt | Not tested | Not tested | Max 0.003% |
| Loss on drying | Max 0.5% | Per monograph | Max 0.5% |
| Residue / sulphated ash | Residue on ignition max 0.2% | Per monograph | Sulphated ash max 0.2% |
| Particle size | D90 max 20 micrometre | Confirm on enquiry | 90% below 20 micrometre |
Three observations follow, and they are the ones worth carrying into a negotiation. First, the veterinary grade is not simply a looser version of the human one: it drops the named impurities, the residual solvents and the genotoxic control, but adds an iron test that the human grade does not have. Second, the human grade controls both sides of the assay because a formulated dose depends on the content being close to label; the veterinary grade only sets a floor. Third, particle size is common to both – micronisation is a functional requirement of the molecule, not a grade differentiator.
Why the impurity list is longer than the limit table suggests
| Impurity | USP limit (human) | What it is, and why it is named |
|---|---|---|
| Albendazole oxide and albendazole sulfone | Combined max 0.4% | Oxidative degradation products; the sulfoxide is also the active metabolite, so this limit serves stability and pharmacology at once |
| Fenbendazole related compound A | Max 0.23% | A structurally close analogue – fenbendazole differs from albendazole only in the thio side chain, so its related compounds are credible impurities in a shared-chemistry plant |
| Fenbendazole related compound B | Max 0.15% | As above |
| Albendazole related compound A | Max 0.15% | Defined process impurity from the ring-closure chemistry |
| Albendazole related compound F | Max 0.5% | The largest single limit in the set – worth asking why, since it suggests a characteristic by-product of the commercial route |
| Albendazole ethyl carbamate | Max 0.15% if present | A carbamate with a potential genotoxicity concern. It is controlled as a specified impurity rather than being left to the unspecified limit, because a generic 0.10% threshold is not an appropriate control for a genotoxic substance |
| Any unspecified impurity | Max 0.10% | The catch-all qualification threshold |
| Total impurities | Max 0.8% | Summed profile, the figure to trend across deliveries |
The presence of fenbendazole related compounds on an albendazole monograph is a useful reminder of how these products are actually made: the same plant, the same chemistry and often the same equipment produce both molecules, and the monograph protects against that reality rather than pretending it does not exist.
Particle size: the specification both grades share
Albendazole is practically insoluble in water. Dissolution, not permeability, is the rate-limiting step, which places it in BCS Class II and makes particle size a functional property rather than a cosmetic one. Reducing D90 below 20 micrometre increases the specific surface area available to the dissolution medium, and that is what the formulation relies on.
| Issue | What happens | What to do |
|---|---|---|
| Coarse material delivered | Slower dissolution, lower and more variable exposure from the same labelled dose | Test the particle size distribution on arrival, not only the assay |
| Over-micronisation | Agglomeration, poor flow and dust in handling | Specify a distribution (D90 and the 90% criterion), not just a mean |
| Milling without a stability check | Localised heat and oxidation during micronisation, raising the sulfoxide and sulfone | Re-test the oxidative impurities after milling, not only before |
| Polymorph change during processing | Different dissolution behaviour for the same particle size | Confirm the polymorphic form your formulation was developed on |
Applications in brief
| Sector | Dosage forms | Grade used |
|---|---|---|
| Human medicine | Tablets and chewable tablets for intestinal nematode infections; longer-course therapy for tissue-dwelling larval disease | USP or EP |
| Veterinary – large animals | Oral drenches, boluses and feed premixes for cattle, sheep, goats and horses | Veterinary |
| Veterinary – companion animals | Tablets and palatable formulations for dogs and cats | Veterinary |
| Veterinary – swine and poultry | Premix and water-dispersible formats | Veterinary |
We describe the API and its specifications. We do not make therapeutic claims for the material, and the indications, dose and formulation are the responsibility of the marketing authorisation holder in each market.
Regulatory and documentation
| Framework | What applies | What to confirm |
|---|---|---|
| Human API | GMP expectations for API manufacture; compendial compliance with USP or EP | The monograph edition, and whether your market requires a certificate of suitability or a national registration |
| Veterinary API | Veterinary medicines regulations in the destination market; feed-additive rules where relevant | Which grade the registration was written against |
| TSCA / REACH | Inventory and registration status for CAS 54965-21-8 | Confirmed on enquiry – it is your registration that has to match |
| Residual solvents | ICH Q3C Class 2 limits for methanol and toluene | Reported on the human grade certificate |
| Genotoxic impurities | Assessment of the carbamate impurity against the applicable guidance | A stated limit and result on the certificate, not a generic statement |
| Transport and storage | Non-hazardous in the packed form supplied | Protect from light and moisture in transit; confirm with your forwarder |
Buying checkpoint
| Item | What to fix in writing |
|---|---|
| Grade | USP, EP or veterinary, with the monograph edition named |
| Particle size | The distribution and the criterion – D90 max 20 micrometre, 90% below 20 micrometre |
| Impurity set | The named compounds with their individual limits, plus the unspecified and total limits |
| Residual solvents | Methanol and toluene figures for human grade |
| Iron | Max 0.003% for veterinary grade |
| Documentation | Batch COA against the named specification, SDS, and a grade statement your customer’s audit can accept |
| Packaging | 25 kg fibre drum, double PE liner; confirm liner integrity on arrival |
Frequently asked questions
Can veterinary grade be used for a human product?
No. It is not tested for the named related compounds, the residual solvents or the carbamate impurity, so there is no data on which to release it against a USP or EP specification. The reverse is also true in commercial terms: a human-grade lot satisfies the veterinary limits but costs more than the application requires.
Why does the veterinary grade have an iron test and the human grade does not?
Iron matters in feed and drinking-water applications, where the formulation and the water chemistry interact. For a human tablet the iron contribution is controlled through the excipient and container specifications rather than the API monograph.
Is albendazole sulfoxide an impurity or an active?
Both. It is the principal active metabolite in vivo, and it is also an oxidative degradation product of the API. That is why it is limited on the certificate as well as discussed in the pharmacology.
What does “D90 max 20 micrometre” actually require?
90% of the particles by volume are below 20 micrometre. Ask for the full distribution – a lot can meet D90 while carrying a coarse tail that behaves differently in dissolution.
Do you supply both grades from the same plant?
Confirm the source and the grade traceability per order. Where a supplier runs both, the fenbendazole related-compound limits on the human monograph exist precisely because of that shared chemistry.
Related reading
- Albendazole USP, EP and veterinary grade – product and specifications
- Human versus veterinary grade albendazole: what actually differs
- Albendazole impurity profile and genotoxic control
- Albendazole particle size and dissolution
- Sourcing albendazole API: documentation and supplier checks
- Albendazole oxide (sulfoxide) – impurity reference material