Medical brain notes 14

  INTRODUCTION A plethora of chemical compounds for the determination of small amounts of water present in organic solids, pharmaceutical substances and organic solvents have been devised over a length of time. But unquestionably the most important of these is the one proposed by Karl Fischer (1935), which is considered to be relatively specific for water*. It essentially makes use of the Karl Fischer reagent which is composed of iodine, sulphur dioxide, pyridine and methanol.   Note : Both pyridine and methanol should be anhydrous.   THEORY Water present in the analyte reacts with the Karl Fischer reagent in a two-stage process as shown below : From Eq. ( a ) step l, it is obvious that the oxidation of sulphur dioxide takes place by iodine to yield sulphur trioxide and hydrogen iodide thereby consuming one mole of water. In other words, each one molecule of iodine disappears against each molecule of water present in the given sample. It is pertinent to mention here that ...

  INSTRUMENTATION Figure 14.1 illustrates a simple dead-stop end-point assembly or a Karl Fischer titration apparatus. The titration vessel is fitted with a pair of identical platinum electrodes, a mechanical stirrer with adjustable speed, and a burette. It will be observed that absolutely little or no current may flow unless and until the solution is totally free from any polarizing substances ; this could perhaps be due to the absorbed layers of oxygen and hydrogen on the anode and cathode respectively. However, the current shall flow only when the two electrodes get depolarized. The Karl Fischer reagent is pumped into the burette by means of hand bellows, the eccess of moisture is usually prevented by employing an appropriate arrangement of desiccant tubes. Alternatively, the stirring may also be accomplished either by using a magnetic stirrer or by means of a suitably dried nitrogen passed gently through the solution during the course of titration. The end-point is achieved by ...

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 expr...