Difference Between Water (Moisture) Content and Loss on Drying (LOD)

A lot of pharma professionals have the confusion regarding the concept of water content (moisture content) and loss on drying. Both have a considerable difference to understand.

Water content is determined by the Karl Fischer titration method and it consists of only water i.e moisture content. The results do not contain other volatile matter except the water.

Loss on drying (LOD) is determined by heating the sample below its melting point in an oven and it includes all volatile matter including water content and solvents.
Loss on Drying is an unspecific analytical technique removing not only water but all other volatile impurities like alcohol etc. from a sample.

The degree of drying depends upon, 1) Temperature 2) Drying time
LOD or total moisture content analysis of Pharmaceutical products can include both bound (e.g. water of hydration) & free water.
In cases there are additional traces of other volatile impurities present, like alcohol; LOD may be higher than water content.
In other cases, LOD may be lower than water content, as bound crystal water may not be removed by heating.
% LOD = % Water content - % water molecule in the API
The Loss on Drying Test is designed to measure the amount of water and volatile matters in a sample when the sample is dried under specified conditions. e.g 105°C, 3 hours.

The nature of the drug substance that is to be weighed and used in compounding a prescription must be known exactly. If the substance is a hydrate, its anhydrous equivalent weight may need to be calculated. On the other hand, if there is adsorbed moisture present that is either specified on a certificate of analysis or that is determined in the pharmacy immediately before the drug substance is used by the procedure under Loss on Drying, this information must be used when calculating the amount of drug substance that is to be weighed in order to determine the exact amount of anhydrous drug substance required.