Loss on Drying (LOD) Calculation Formula:
Loss on Drying (LOD) is a common test used in pharmaceutical quality control to determine the amount of volatile matter lost from a sample during drying. It is widely used for APIs, excipients, intermediates, and pharmaceutical products to monitor moisture and other volatile substances present in the material.
Although LOD is often discussed together with water content, the two tests are not exactly the same. LOD measures the total weight loss under specified drying conditions, while water content specifically measures the amount of water present in the sample.
What is Loss on Drying (LOD)?
Loss on Drying is a gravimetric test in which a sample is weighed before and after drying under specified conditions. The decrease in sample weight is reported as a percentage of the original sample weight.
The weight loss can be caused by water as well as other volatile substances such as residual solvents or volatile impurities.
For example, if an API contains 2.0% water and 0.5% of a volatile solvent, the LOD may be approximately 2.5%, depending on the drying conditions.
Therefore:
LOD = Water + Other volatile substances lost during drying
The exact result depends on the temperature, drying time, vacuum condition, sample quantity, and procedure specified in the applicable Pharmacopoeial monograph or analytical method.
Loss on Drying Calculation Formula
The basic LOD calculation formula is:
LOD (%) = [(Weight of sample before drying − Weight of sample after drying) / Weight of sample before drying] × 100
The same calculation can be written using the weights of the weighing bottle or dish.
LOD (%) = [(W2 − W3) / (W2 − W1)] × 100
Where:
- W1 = Weight of empty weighing bottle/dish
- W2 = Weight of weighing bottle + sample before drying
- W3 = Weight of weighing bottle + sample after drying
The denominator, W2 − W1, represents the actual sample weight before drying.
Loss on Drying Calculation Example
Suppose an analyst performs LOD testing for an API.
The following weights are obtained:
- Weight of empty weighing bottle = 25.000 g
- Weight of bottle + sample before drying = 26.000 g
- Weight of bottle + sample after drying = 25.990 g
First, calculate the sample weight before drying:
Sample weight = 26.000 − 25.990 = 1.000 g
Now calculate the weight loss:
Weight loss = 26.000 − 25.990 = 0.01 g
Therefore:
LOD (%) = (0.01 / 1.000) × 100
LOD = 1.0%
So, the Loss on Drying result for the sample is 1.0%
If the specification is NMT 3.0%, the sample complies with the specification.
Another Simple LOD Calculation
Sometimes the calculation can be performed directly using the sample weights.
Suppose:
- Initial sample weight = 2.000 g
- Final sample weight after drying = 1.960 g
Weight lost:
2.000 − 1.960 = 0.040 g
Therefore:
LOD (%) = (0.040 / 2.000) × 100
LOD = 2.0%
The LOD of the sample is therefore 2.0%.
What Does LOD Actually Measure?
LOD does not necessarily represent only water.
During the drying process, several volatile components can be removed from the sample. These may include:
- Water
- Residual organic solvents
- Alcohols
- Other volatile substances
- Certain low-molecular-weight volatile impurities
Therefore, LOD is better understood as the total loss in sample weight under the specified drying conditions.
This is particularly important when working with APIs or excipients that may contain residual solvents or other volatile components.
What is Water Content?
Water content is the specific amount of water present in a material.
Unlike LOD, a water-specific analytical technique is designed to determine water rather than the total volatile weight loss.
One of the most widely used techniques for pharmaceutical water determination is Karl Fischer titration.
Karl Fischer analysis is based on a chemical reaction that is specific to water, making it suitable when accurate determination of water is required.
Water content is generally reported as:
Water content (%) = Amount of water present / Sample weight × 100
For example, if a 1.000 g sample contains 0.010 g of water:
Water content = (0.010 / 1.000) × 100 = 1.0%
Therefore, the water content is 1.0%.
Difference Between LOD and Water Content
The most important difference is that LOD measures weight loss during drying, whereas water content measures water specifically.
| Parameter | Loss on Drying (LOD) | Water Content |
|---|---|---|
| What is measured? | Total weight loss during drying | Water specifically |
| Principle | Gravimetric weight loss | Usually chemical reaction/titration |
| Water measured? | Yes, if water is lost under the conditions | Yes |
| Other volatile substances measured? | Can be measured | Generally no |
| Common technique | Oven or vacuum drying | Karl Fischer titration |
| Result | % loss on drying | % water |
| Specific for water? | No | Yes |
| Main application | Moisture/volatile matter control | Accurate water determination |
LOD vs Karl Fischer Water Content: Practical Example
Consider an API containing:
- Water = 1.2%
- Residual methanol = 0.8%
Suppose both components are lost during the LOD drying conditions.
The approximate LOD could therefore be:
LOD = 1.2 + 0.8 = 2.0%
However, Karl Fischer testing may report:
Water content = 1.2%
This demonstrates an important concept:
LOD = Water + other volatile substances lost during the test
while:
Water content = Water specifically
The two results may therefore be different.
When Should LOD Be Used?
LOD is useful when the specification or analytical procedure is intended to control the overall loss of volatile matter.
It is commonly used for:
- APIs
- Pharmaceutical excipients
- Powders
- Granules
- Certain finished products
- Raw materials
- Intermediates
The exact drying conditions should always follow the applicable monograph or approved analytical procedure.
Frequently ask FAQ
1. What is the formula for LOD?
LOD (%) = [(Initial weight − Final weight) / Initial weight] × 100.
2. What does LOD measure?
LOD measures the total weight loss from a sample under specified drying conditions.
3. Is LOD the same as water content?
No. LOD can include water and other volatile substances, while water content specifically measures water.
4. What is the most common method for water determination?
Karl Fischer titration is widely used for specific water determination.
5. Can residual solvent affect LOD?
Yes. Volatile residual solvents can increase the LOD result.
6. Can LOD be lower than water content?
It can occur depending on the analytical procedures and how completely water is released or measured.
7. Why is LOD performed in pharmaceuticals?
It helps control moisture and other volatile matter in pharmaceutical materials.
8. What is the unit of LOD?
LOD is normally reported as percentage (% w/w).
9. Does higher LOD always mean higher water?
No. Other volatile substances can also contribute to LOD.
10. Which is better, LOD or Karl Fischer?
It depends on the purpose. LOD measures total loss during drying, while Karl Fischer is preferred when specific water determination is required.