Assay on Anhydrous Basis

Assay on anhydrous basis states how much active ingredient a material holds as if it contained no water. The powder is not dry; the figure combines an assay and a water determination. The United States Pharmacopeia (USP) calls a correction for water "anhydrous basis" and a correction for loss on drying "dried basis" (USP 38–NF 33 General Notices, 6.40, Dried, Anhydrous, Ignited, or Solvent-Free Basis).

A hydrate (a crystal that holds water in its structure) shows why the label matters. A pure monohydrate carries one molecule of water for every molecule of the substance, so even a flawless lot assays below 100% as-is while it assays 100% on the anhydrous basis. Reading a low as-is figure as a failed purity test misreads the basis.

Multiply the as-is assay by 100 and divide by 100 minus the water percentage. To go back, multiply the anhydrous assay by 100 minus the water percentage and divide by 100.

Converting between as-is and anhydrous assay

• Anhydrous assay (%) = as-is assay (%) × 100 ÷ (100 − water %)
• As-is assay (%) = anhydrous assay (%) × (100 − water %) ÷ 100

A published example uses an as-is assay of 93.5% and 6.0% water: 93.5 × 100 ÷ 94 = 99.47% (Journal of Pharmaceutical Compounding and Therapeutics, 2024). Run backward, 99.47 × 94 ÷ 100 = 93.5%. The material did not become purer; the basis changed.

Divide the target mass by the anhydrous assay as a fraction, then by the fraction of the powder that is not water. Skipping the water step leaves the batch short by the water percentage.

Weigh-out card:

• Inputs: assay 99.5% (anhydrous basis), water 8.0%, target 100.0 g of active ingredient on the anhydrous basis.
• Water step: 1 − 0.080 = 0.920. Assay step: 0.995.
• Powder to weigh: 100.0 ÷ (0.995 × 0.920) = 109.24 g.
• Skipping the water step gives 100.0 ÷ 0.995 = 100.50 g, which is 8.0% short of 109.24 g.
• If the COA reports an as-is assay, the water already sits inside it: divide by the assay only.

Keep the batch record on the basis the product specification declares for the active ingredient.

The assay and the water test each carry measurement error, and the conversion magnifies both by 100 ÷ (100 − water %), so results drift toward or past specification limits (Indian Journal of Pharmaceutical Sciences, 2009). Arithmetic from that factor: 1.064 at 6.0% water and 1.087 at 8.0%.

A value a little above 100% is therefore possible. Check the water result and the lot pairing before accepting or rounding it. Three errors recur:

• Treating the anhydrous figure as the strength of the powder.
• Treating loss on drying as water, when it also counts other volatiles.
• Pairing an assay and a water result from different lots.

A COA is usable when each assay value carries its basis, a water result for the same lot, and a conversion you can reproduce. Four tests:

1. Basis printed. Pass: "as is", "dried" or "anhydrous" sits beside every assay. Fail: a bare percentage.
2. Water on the same lot. Pass: a water value with its method and the same lot number (in USP 35, 2012, Method I of chapter 921 is Karl Fischer titration). Fail: no water value, or another lot.
3. Reproducible. Pass: your formula result matches the printed anhydrous value within 0.1 percentage point (recommended tolerance). Fail: a larger gap; ask for the calculation.
4. Right correction. Pass: an "anhydrous" claim rests on a water test. Fail: "anhydrous" with only loss on drying reported.

The API quality testing guide covers the tests behind a COA.

The USP 38 text reads a result as-is unless a monograph (the pharmacopeia's published specification for a substance) states another basis, and allows the assay to run on undried material and be calculated on the anhydrous basis when the monograph includes a water test. Some COAs print "anhydrous, solvent-free", which also removes residual solvents (Dong, Chromatography Online, 2024).

Loss on drying measures weight lost on heating; Karl Fischer titration measures water alone.

• Myth: An anhydrous-basis assay of 99.5% means the powder in the drum is 99.5% active. Fact: The figure is calculated as if the water were removed, so the powder as received holds less active ingredient than the printed percentage.
• Myth: "Anhydrous" and "dried" mean the same thing on a COA. Fact: Anhydrous removes water only, while dried removes everything lost on drying, including other volatiles.
• Myth: A hydrate that assays below 100% as-is has failed its purity test. Fact: A pure monohydrate assays 100% on the anhydrous basis, so the lower as-is figure reflects the water in its structure.

Aarise Pharmaceuticals supplies bulk APIs to qualified B2B buyers, quoted product by product. To request a quote, send the API name or CAS (Chemical Abstracts Service) number, quantity, destination, grade or purity, documents needed, payment terms and Incoterms (standard international trade terms). Sample and evaluation quantities are available to qualified buyers, subject to the API, availability and regulations, and documentation may include the COA, specification and SDS/MSDS (safety data sheet) where applicable. Run the four tests on any COA you receive, Aarise's included.

Contact sunil@aarisepharma.com, WhatsApp +91 9899783330, or the contact page.