LOD Adjustment — Translating Moisture Results into Usable Potency Data

This topic is part of the SG Systems Global regulatory & operations glossary.

Updated November 2025 • Potency Basis, Batch-Specific Potency, Potency Adjustment Factor, Karl Fischer Titration • Moisture, Assay, Basis, GMP

LOD adjustment is the use of loss-on-drying (LOD) moisture results to convert between different potency bases (as-is, dry, anhydrous) so that assay values can be used correctly in batching and potency calculations. LOD tells you how much of a material’s mass is volatile (usually water). LOD adjustment applies that information to assay results, allowing manufacturers to express potency on the basis required by specifications, formulations and label claims. Without LOD-adjusted values, the same “98 % assay” can lead to different dose decisions depending on unspoken assumptions about moisture.

“LOD is just a number until you use it. LOD adjustment is where moisture stops being a lab detail and starts affecting what goes into the batch.”

1) What Is Loss-On-Drying (LOD)?

Loss-on-drying (LOD) is a gravimetric test that measures how much weight a sample loses when it is heated under defined conditions. The loss is usually attributed to water and volatile components. LOD is reported as a percentage of the original sample mass (for example, “LOD: 3.0 % w/w”). The test conditions (temperature, time, vacuum) are specified in pharmacopeial monographs or internal methods, and they strongly influence the result.

In batch records and CoAs, LOD appears as a standalone moisture parameter. On its own, it does not say anything about potency. But when combined with chemical assay results, LOD enables conversion between potency bases, allowing manufacturers to express active strength on an as-is, dry or anhydrous basis depending on regulatory and formulation requirements. This conversion step – LOD adjustment – is what allows moisture to be reflected correctly in potency calculations instead of being silently ignored or double-counted.

2) Why LOD Adjustment Matters for Potency and Dose

Many regulated materials contain non-trivial moisture: APIs, excipients, premixes, botanical extracts, vitamins and granulates may all absorb or lose water during manufacture and storage. If moisture is not accounted for, a scale reading of 10.0 kg of “API” might represent 9.7 kg of active and 0.3 kg of water in one lot, but 9.9 kg of active and 0.1 kg of water in another.

Regulators care about dose, not gross mass. Specifications and label claims are often written on a dry or anhydrous basis to provide a stable reference independent of moisture swings. LOD adjustment bridges the gap: it converts assay results (which may be reported on one basis) into the basis used in the specification and the recipe formulation. Without LOD adjustment, batch-specific potency and potency adjustment factors will be inconsistent, and investigators will struggle to reconcile potency data across lots and time.

3) As-Is vs Dry-Basis Potency and the Role of LOD

Assay can be reported on an as-is basis or a dry basis. LOD is the bridge between them. If LOD is 3.0 % and the assay is 95.0 % on an as-is basis, the dry-basis assay can be calculated as:

• Dry-basis assay = As-is assay ÷ (1 – LOD fraction)
• Dry-basis assay = 95.0 % ÷ (1 – 0.03) ≈ 97.94 %

Conversely, if the specification is written on a dry basis and the lab reports 98.0 % on a dry basis with LOD of 2.0 %, the as-is assay is:

• As-is assay = Dry-basis assay × (1 – LOD fraction)
• As-is assay = 98.0 % × (1 – 0.02) ≈ 96.04 %

LOD adjustment automates these conversions so that MES and ERP always use the correct potency value for the basis they are working with. It prevents situations where lab and manufacturing think they are using the same potency number, but one is silently on a dry basis and the other is treated as as-is. That kind of basis mismatch is a classic root cause behind unexplained assay drift and yield anomalies.

4) LOD Adjustment and Batch-Specific Potency

Batch-specific potency is the lot-level strength used in manufacturing systems. LOD adjustment is usually applied at the point where lab results are transformed into that batch-specific potency attribute. A typical sequence is:

• The lab measures LOD and chemical assay on the sample.
• The specification defines whether potency must be expressed on an as-is, dry or anhydrous basis.
• LOD adjustment converts the assay into the required basis.
• The resulting potency (value and basis) is stored as batch-specific potency for the lot.

Once stored, this potency figure is used by potency adjustment factors, batch weighing and corrected active content calculations. LOD itself may also be stored as a separate attribute for trending and stability purposes, but the potency used for dose is already moisture-adjusted according to the agreed basis. This separation allows manufacturers to trend moisture behaviour over time while still dosing against potency values that align cleanly with specifications and formulations.

5) Karl Fischer vs LOD — Different Methods, Same Adjustment Principle

Moisture can be measured by simple LOD ovens or by Karl Fischer titration. From an LOD-adjustment perspective, both are simply ways of obtaining a moisture fraction. The adjustment logic – converting as-is to dry basis or vice versa – is the same. What changes is the level of specificity, sensitivity and selectivity for water versus other volatiles.

In some monographs, “LOD” is defined using a specific procedure that may remove both water and other volatiles. In others, Karl Fischer is used to measure water specifically, while LOD captures broader volatile loss. The key design choice is which moisture result is referenced in potency calculations and documented in specifications. Once that is chosen, LOD adjustment should consistently reference the same moisture value – not switch unpredictably between LOD and Karl Fischer for the same material without clear documentation and change control.

6) LOD Adjustment and Potency Basis for Hydrates

Some materials are intentionally hydrated (for example, monohydrates, dihydrates). For these, specifications may require assay on an anhydrous basis, even though the supplied material always contains bound water of crystallisation. LOD adjustment may be combined with stoichiometric calculations to translate between:

• as-is assay and LOD;
• dry-basis assay (excluding free water);
• anhydrous assay (excluding both free water and bound hydration water).

In these cases, the LOD value typically represents free water, not necessarily all bound water. Monographs may define calculation factors that convert between the hydrate and the anhydrous form. The LOD-adjusted potency on an anhydrous basis then becomes the value used for potency adjustment factors and corrected active content. The important point is that the underlying moisture measurement and the basis used in calculations match what is required by the specification and label claim, not a convenient local simplification.

7) LOD Adjustment Feeding Potency Adjustment Factors and Targets

Once assay results have been LOD-adjusted to the correct basis, they feed directly into potency adjustment factors. In the simplest case, the factor is:

• Factor = Reference potency / LOD-adjusted batch potency

For example, if the reference potency is 100 % dry basis and the LOD-adjusted potency for the lot is 97.9 % dry basis, the factor is 100/97.9 ≈ 1.0215. This factor then scales the theoretical quantity in the recipe to determine the target for batch weighing. The LOD adjustment has already “removed” the moisture from the potency figure, so the gross weight target compensates both for assay and moisture in one step.

By capturing LOD-adjusted potency as a stable, basis-specific value in master data, the execution system can focus on applying the factor and recording targets and actuals, rather than repeatedly re-computing basis conversions at the point of use in uncontrolled ways.

8) LOD Adjustment in Percent-Solids and Liquid Systems

For solutions, slurries and suspensions, moisture is often expressed as % solids basis rather than LOD. However, some concentrates and pastes are still controlled via LOD-style tests, particularly when they behave more like damp solids than true solutions. In these cases, LOD adjustment can help convert between “wet” and “dry” composition when designing concentration-adjusted charges.

For example, a paste might be tested with LOD to determine its non-volatile solids fraction, and assay may be expressed on a solids basis. LOD adjustment can then be used to determine how much dry solid – and how much active within that solid – is delivered per kilogramme of paste. This enables more accurate batch calculations and aligns the behaviour of pastes with that of powders and premixes in potency-adjusted batching strategies.

9) LOD Adjustment and Test-Driven Setpoint Adjustment

In test-driven setpoint adjustment, multiple in-process tests (assay, LOD, % solids, titer, pH) can drive changes to setpoints and batch targets. LOD adjustment ensures that moisture results enter those calculations on a consistent, traceable basis.

For example, a granulate might be dried to a target LOD window before being charged into a final blend. If the LOD is slightly higher than expected, the system may:

• derive a lower dry-basis potency via LOD adjustment;
• update the potency adjustment factor; and
• increase the gross addition to maintain corrected active content.

Alternatively, if the process design does not permit further additions, elevated LOD might trigger an in-process assay gate or a hold decision. In both scenarios, LOD adjustment is the mechanism that turns “LOD = 4.5 %” into operational consequences in a controlled, documented way rather than leaving it as a passive number in a lab report.

10) Data Integrity, Analytical Lot Links and Audit Trails

Because LOD adjustment directly affects potency, it is GxP-relevant and must meet ALCOA+ expectations. Good practice includes:

• Capturing LOD results as structured data in LIMS or equivalent systems.
• Linking LOD and assay results to each lot via an analytical lot link.
• Performing LOD adjustment in validated calculations, not in local spreadsheets.
• Storing LOD-adjusted potency (value and basis) as part of batch-specific potency master data.
• Recording calculation inputs and results in the electronic batch record (eBMR) with audit trails.

When auditors ask how moisture was handled in potency calculations, organisations should be able to show the LOD result, the basis of the specification, the LOD-adjustment calculation, the resulting potency and the impact on targets and corrected active content. This clear chain of evidence is a key part of defending dose decisions and process capability assessments.

11) Typical Use Cases Across Industries

LOD adjustment is used across a wide range of potency-critical materials and sectors:

• Pharmaceuticals and biologics: APIs, intermediates, granulates, lyophilised materials and excipients where moisture varies between lots or over time.
• Dietary supplements: botanical powders, vitamin premixes and probiotic blends where moisture affects potency and stability.
• Food and beverage: enzyme powders, baking improvers and fortification mixes controlled by both LOD and assay or activity units.
• Cosmetics and personal care: active powders and premixes where performance and label limits depend on dry or anhydrous potency.
• Chemicals and speciality materials: catalysts and performance additives where both moisture and potency drive activity and shelf life.

In each setting, LOD adjustment is not a standalone “lab trick”; it is integrated into the way potency is stored, the way batches are dosed and the way mass balance and yield are interpreted across campaigns and stability studies.

12) Common Pitfalls and Failure Modes

When LOD and potency are not handled consistently, a number of predictable issues arise:

• Ignoring LOD: using as-is assay directly in potency calculations while specifications are written on a dry basis.
• Hidden conversions: ad-hoc LOD adjustments in spreadsheets that are not reflected in master data or eBMRs.
• Mixed moisture methods: switching between LOD and Karl Fischer without clearly documenting which result is used for potency.
• Unclear basis: CoAs that report “assay: 98 %” and “LOD: 3 %” without stating whether the assay is as-is or dry-basis.
• Inconsistent implementation: applying LOD adjustment for some materials and not for others with similar moisture behaviour, leading to inconsistent yield and assay behaviour.

These problems often surface in OOS, OOT and deviation investigations, where gross-weight records cannot be reconciled with finished-product assay results without revisiting forgotten or undocumented LOD conversions. Formalising LOD adjustment as part of potency management prevents this recurring pattern.

13) Practical Implementation Steps

To implement LOD adjustment in a robust, audit-ready way, organisations typically:

• Identify materials where moisture significantly affects potency or performance.
• Clarify for each material whether specifications are on an as-is, dry or anhydrous basis.
• Standardise how LOD (or Karl Fischer) results are obtained and recorded in LIMS or equivalent systems.
• Define and validate LOD-adjustment calculations that convert assay to the required potency basis.
• Integrate LOD-adjusted potency into batch-specific potency, potency adjustment factors, corrected active content and related MES/ERP calculations.

Once these steps are complete, LOD adjustment becomes part of the normal analytical-to-execution data flow. Moisture is no longer a stray line in a test report; it is embedded directly in how dose is set, how yield is interpreted and how the control strategy is explained to regulators and customers.

FAQ

Q1. Is LOD always measuring only water?
No. LOD measures loss of mass under defined conditions and may include water and other volatiles. If water-specific data are required, Karl Fischer titration is often used alongside or instead of LOD.

Q2. Do all materials need LOD adjustment for potency?
No. LOD adjustment is most important when moisture meaningfully affects dose, label claim or performance. For very low-moisture, low-variability materials, it may be sufficient to work directly with as-is assay, provided this is consistent with the specification and control strategy.

Q3. Where should LOD adjustment be performed – in the lab or in MES?
The underlying calculations should be defined and validated centrally. In many organisations, LOD-adjusted potency is calculated and stored in LIMS or master data, then passed into MES. The critical point is that the calculation is controlled and traceable, not that it occurs in a particular system.

Q4. How should LOD and potency appear on a CoA?
Certificates of analysis should clearly state both the LOD value and the basis of the potency (for example, “Assay: 98.0 % on dry basis; LOD: 2.5 %”). This allows manufacturing systems to interpret and, if necessary, re-check LOD adjustments.

Q5. What is a practical first step to improve LOD adjustment?
Start by listing all materials where both LOD and assay are reported. For each, confirm the intended potency basis in specifications and recipes, then ensure that LOD-adjusted potency is calculated consistently and stored as part of batch-specific potency before it is used in dosing calculations.

Related Reading
• Potency & Basis: Potency Basis | Batch-Specific Potency | Potency Adjustment Factor | Potency / Assay Adjustment
• Moisture & Solids: Karl Fischer Titration | % Solids Basis | Concentration-Adjusted Charge
• Yield, Mass Balance & Records: Mass Balance | Potency-Normalised Yield | Active-Equivalent Consumption | Electronic Batch Record (eBMR)