Loss on drying (LOD) is a fundamental gravimetric test used to determine the amount of moisture and other volatile matter released by a sample under controlled heating conditions. This article provides a complete, step-by-step loss on drying test procedure, covering required equipment, sample preparation, drying parameters, calculation formulas, and alignment with major standards such as USP, Ph. Eur., GB/T, ASTM, and JIS. It is a practical reference for laboratory technicians and quality professionals in the pharmaceutical, food, chemical, and polymer industries.
Technical Overview
Loss on drying (LOD) is a quantitative analytical method that measures the mass lost by a sample when it is heated under specified conditions. The weight loss reflects the total volatile content of the material, which typically consists of free water, absorbed moisture, and low-boiling solvents. The result is expressed as a percentage of the original sample mass and serves as a key quality attribute for solids, powders, granules, and semi-solid materials.
The test is governed by several internationally recognized compendial and industry standards, including USP General Chapter <731> Loss on Drying, Ph. Eur. Method 2.2.32, the Chinese Pharmacopoeia (ChP) Method 0831, GB/T 6284 for industrial chemical products, ASTM D6980 for polymeric materials, and JIS K 0068 for general chemical products. Unless otherwise specified in an individual monograph or product specification, the default condition is drying at 105 °C to constant weight.
It is important to distinguish loss on drying from Karl Fischer water content determination. LOD is a non-selective gravimetric method that captures all volatile substances, whereas Karl Fischer titration selectively measures water molecules through a chemical reaction. For many routine quality control purposes, LOD is preferred because it is simple, fast, inexpensive, and does not require chemical reagents.
Testing Samples
Pharmaceutical Solids
Active pharmaceutical ingredients (APIs), excipients such as lactose, microcrystalline cellulose and starch, wet granulations, and finished dosage forms are routinely tested for loss on drying. Excess moisture in these materials can promote hydrolysis, microbial growth, tablet softness, and reduced shelf life, so LOD limits are commonly specified in monographs and batch release specifications.
Food and Agricultural Products
Powdered foods, milk powder, flour, starches, spices, dehydrated vegetables, and feed ingredients are tested to verify moisture-related shelf life, labeling compliance, and processing behavior such as flowability and caking tendency.
Chemical Raw Materials and Inorganic Salts
Industrial chemicals, fertilizers, catalysts, dyes, and mineral powders are evaluated for residual moisture and volatile matter, which affect assay values, stoichiometry, storage stability, and commercial valuation.
Polymer Resins and Plastic Materials
Thermoplastic resins such as PA, PC, PET, and ABS are tested for moisture before injection molding or extrusion, because excessive residual moisture causes hydrolytic degradation, silver streaks, and mechanical defects in molded parts.
Viscous Liquids and Semi-Solids
Syrups, ointments, gels, and adhesive materials can be tested by spreading a thin, uniform layer over an inert support such as clean sand or a glass fiber pad inside the weighing container, ensuring complete evaporation of volatiles.
Testing Items
The core parameters determined through the loss on drying test procedure include:
- Loss on drying, expressed as percentage by mass of the sample before drying
- Moisture and volatile matter content of raw materials and finished products
- Drying to constant weight, used as an endpoint criterion
- Residual moisture after drying, granulation, or freeze-drying processes
- Total solids content, calculated as 100 percent minus the LOD value
Typical acceptance limits vary by material class. Many pharmacopoeial substances specify LOD limits between 0.5 percent and 5.0 percent, while polymer resins used in precision molding may require values below 0.02 percent. The applicable limit must always be taken from the relevant monograph, product standard, or customer specification.
Testing Methods
Equipment and Materials Required
A compliant loss on drying determination requires the following laboratory equipment:
- Analytical balance with a readability of 0.1 mg, calibrated and verified regularly
- Forced-convection drying oven capable of maintaining the target temperature within ±2 °C, ideally with a calibrated temperature mapping record
- Vacuum drying oven for heat-sensitive samples, capable of operating at reduced pressure
- Desiccator charged with freshly activated silica gel or phosphorus pentoxide desiccant
- Glass weighing bottles with lids, evaporating dishes, or shallow covered dishes of suitable size
- Clean, dry tools such as spatulas, laboratory tongs, and lint-free gloves
Sample Preparation Steps
Before the test begins, follow these preparation steps to ensure representative and reproducible results:
- Ensure the sample is homogenized; gently crush large crystals or agglomerates to accelerate moisture release without generating excessive heat or friction
- Condition the weighing containers by pre-drying them at the test temperature, typically for at least one hour
- Confirm that the desiccant in the desiccator is active and has not reached saturation
- Allow refrigerated or frozen samples to equilibrate to room temperature in a sealed container before opening, to prevent condensation
- Minimize sample exposure to laboratory air, particularly for hygroscopic materials
Standard Oven Drying Procedure (Step by Step)
The following sequence reflects the conventional gravimetric procedure described in pharmacopoeial and national standards:
- Step 1: Place the clean, empty weighing bottle with its lid opened in the drying oven at 105 °C for at least one hour to pre-dry the container.
- Step 2: Transfer the bottle to the desiccator, close the lid, and allow it to cool to room temperature for approximately 30 to 45 minutes.
- Step 3: Accurately weigh the cooled container with its lid using the analytical balance and record this mass as m0.
- Step 4: Add the specified quantity of sample, typically 1.0 g to 2.0 g weighed to ±10 percent of the target, into the container and distribute it as an even layer not exceeding 5 mm in thickness, or 10 mm for bulky or fluffy materials. Accurately weigh the container plus sample and record the mass as m1.
- Step 5: Place the opened bottle and its lid in the oven at the specified temperature, normally 105 °C, and dry for the specified time, usually one hour for the first cycle.
- Step 6: Remove the bottle from the oven, promptly cover it with the lid, and cool it in the desiccator for 30 to 45 minutes until it reaches room temperature.
- Step 7: Accurately weigh the covered, cooled container and record the mass as m2.
- Step 8: Return the open bottle to the oven for an additional drying cycle of approximately 30 to 60 minutes, then repeat cooling and weighing until constant weight is achieved, meaning the difference between two consecutive weighings does not exceed 0.3 mg unless otherwise specified.
- Step 9: Record all masses, environmental conditions, drying temperature, and total drying time in the test log for full traceability.
Vacuum Drying Procedure for Heat-Sensitive Samples
Substances that melt, decompose, or undergo chemical change at 105 °C should be dried in a vacuum oven at a reduced temperature, commonly between 60 °C and 80 °C, under a pressure of approximately 2.7 kPa (20 mmHg) or below. Extremely thermolabile materials may be dried over phosphorus pentoxide desiccant at room temperature under vacuum, with the drying endpoint confirmed gravimetrically. All modified conditions must be justified in the method or product specification.
Rapid Alternative Methods
For high-throughput incoming material checks, halogen or infrared moisture analyzers can deliver LOD-equivalent results in 5 to 15 minutes. These instruments must be calibrated against the reference oven method for each specific matrix, and the drying program must be validated to demonstrate equivalent results. Thermogravimetric analysis (TGA) may also be used for very small sample quantities, monitoring mass loss continuously as temperature ramps.
Calculation Formula and Result Expression
The loss on drying result is calculated using the following formula:
LOD (%) = (m1 − m2) / (m1 − m0) × 100
In this expression, m0 is the mass of the empty dried container, m1 is the mass of the container plus the sample before drying, and m2 is the mass of the container plus the sample after drying to constant weight. Results are reported to two decimal places. Duplicate determinations should agree within the precision limits defined by the method, and the mean value is compared against the applicable acceptance criterion.
Critical Precautions and Common Error Sources
To maintain accuracy and reproducibility, laboratories should control the following factors:
- Uniform sample thickness, because thick layers trap moisture and bias results low
- Consistent lid handling, keeping lids open during drying and closed during cooling and weighing to prevent moisture re-absorption
- Effective desiccant, replacing or regenerating silica gel before saturation
- Avoidance of over-drying, which can cause decomposition or loss of crystal water and falsely elevate the result
- Calibrated oven temperature and balance performance, verified through a documented calibration program
- Protection of hot containers with gloves or tongs to prevent fingerprints and heat transfer to the balance
- Minimized exposure time of hygroscopic samples to ambient air during handling
Applications
Loss on drying testing is applied extensively across regulated and industrial sectors:
- Pharmaceutical quality control: raw material release, in-process moisture checks during granulation and drying, batch release, and stability studies
- Food manufacturing: moisture verification for shelf life, nutritional labeling, drying process control, and prevention of caking and spoilage
- Chemical and fertilizer production: assay correction, packaging verification, and trade settlement based on dry weight
- Plastics processing: pre-molding moisture verification of engineering resins to prevent hydrolytic degradation and surface defects
- Cosmetics and personal care: stability assessment of powders, soaps, and surfactant-based products
- Environmental and agricultural testing: determination of solids content in soils, sludges, and biomass materials
Manufacturers frequently delegate confirmatory testing to accredited third-party laboratories, which perform the procedure under ISO/IEC 17025-aligned quality systems with validated equipment and documented traceability.
FAQ
What does "drying to constant weight" mean?
Constant weight is achieved when the difference between two consecutive weighings, after repeated drying and cooling cycles, does not exceed a defined threshold, typically 0.3 mg for pharmacopoeial samples. Reaching constant weight confirms that volatiles have been fully removed under the chosen conditions.
What is the difference between loss on drying and water content?
Loss on drying measures all volatile substances, including water, residual solvents, and other evaporating compounds, through weight loss. Water content determined by Karl Fischer titration measures only water through a selective chemical reaction. For samples containing volatile solvents, the two values will differ, and the appropriate method should be selected based on the product specification.
Why is 105 °C the default drying temperature?
A temperature of 105 °C is high enough to drive off free and surface moisture efficiently, yet gentle enough to avoid significant decomposition for most crystalline and amorphous solids. It serves as the harmonized default in major pharmacopoeias, while individual monographs may prescribe lower temperatures or vacuum conditions for sensitive materials.
How much sample should be used for the test?
Unless otherwise specified, 1.0 g to 2.0 g of sample is used, weighed accurately to within ±10 percent of the stated amount. The sample must be spread thinly and evenly so that moisture can escape completely during drying.
Why must the sample be cooled in a desiccator before weighing?
A hot container creates convection currents around the balance pan that cause unstable and inaccurate readings, and warm samples can re-absorb atmospheric moisture during cooling. A sealed desiccator with active desiccant allows the container to cool in a dry environment, protecting the result from both effects.
How long does the full procedure take?
A single cycle of drying, cooling, and weighing usually requires 1.5 to 2 hours, and achieving constant weight may extend the total time to 3 hours or more. Rapid moisture analyzers can shorten routine checks to under 20 minutes once the program has been validated against the reference method.
Which standard should my laboratory follow?
The choice depends on the product and market. Pharmaceutical materials are tested under USP, Ph. Eur., or ChP monographs; industrial chemicals follow GB/T, ASTM, or JIS methods; and polymer resins are typically assessed using ASTM procedures. When multiple standards apply, the strictest or contractually specified method should govern the testing.