Applications of Karl Fischer Method for Determination of Water in Pharmaceutical Analysis

APPLICATIONS OF KARL FISCHER METHOD FOR DETERMINATION OF WATER IN PHARMACEUTICAL ANALYSIS

The Karl Fischer method for the determination of water is used for prednisolone sodium phosphate as described below.

1. PREDNISOLONE SODIUM PHOSPHATE

Materials Required : Karl Fischer Reagent* : 100 ml ; prednisolone sodium phosphate : 0.2 g ; anhydrous methanol : 20.0 ml.

Procedure : Add about 20 ml of anhydrous methanol to the titration vessel and titrate to the amperometric end-point with the Karl Fischer reagent. Quickly add 0.2 g of prednisolone sodium phosphate sample, stir for 1 minute and again titrate to the amperometric end-point with the Karl Fischer reagent. The difference between the two titrations gives the volume (v) of Karl Fischer reagent consumed by the sample.

The minimum water equivalent is 3.5 mg of water per ml of Karl Fischer reagent. Hence, the percentage of water w/w in the given sample may be calculated by the following expression :

Precautions :

·              The reagents and solutions used must be kept anhydrous and necessary care should be taken through-out to prevent exposure to atmospheric moisture,

·              The Karl Fischer reagent should be protected from light and preferably stored in a bottle fitted with an automatic burette, and

·              The water equivalent of Karl Fischer reagent should always be determined before use.

2. COGNATE ASSAYS

A number of other official pharmaceutical substances may be assayed for their water content by the Karl Fischer method as summarized in the following Table 14.1.