卡尔费休水分测定仪性能确认

KARL FISHER APPARATUS AND ITS PERFORMANCE VERIFICATION

R ICK J AIRAM, R OBERT M ETCALFE, P H.D., AND Y U-H ONG T SE, P H.D. GlaxoSmithKline Canada, Inc.

14.1 INTRODUCTION

The Karl Fisher titration is one of the most common and most sensitive methods used in the analytical laboratory. The titrimetric determination of water is based on the quantitative reaction of water with an anhydrous solution of sulfur dioxide and iodine in the presence of a buffer that reacts with hydrogen ions. This titration is a two-stage process:

SO2 + MeOH + RN→(RNH)SO3Me (14.1)

(RNH)SO3Me + I2 + H2O + 2RN→(RNH)SO4Me + 2(RNH)I (14.2)

where RN is a base, typically pyridine or imidazole. Reaction (14.1) reaches equilibrium and produces methylsulfite as the reaction intermediate. Reaction (14.2) the redox process, is very rapid. From equation (14.2) the direct relation between water and iodine consumption can be seen, which enables the amount

of water to be determined. Complete esterification of the sulfur dioxide with the alcohol, and the ability of the base to neutralize the methyl sulfurous acid, are

the key requirements for the reaction above to be stoichiometric.

Analytical Method Validation and Instrument Performance Verification, Edited by Chung Chow Chan, Herman Lam, Y. C. Lee, and Xue-Ming Zhang

ISBN 0-471-25953-5 Copyright 2004 John Wiley & Sons, Inc.

221

222 KARL FISHER APPARATUS AND ITS PERFORMANCE VERIFICATION

Pyridine was used in the beginning of the development of the method. The reaction was slow and the endpoint unstable because of weak basicity of pyridine. The pyridine system buffers at about pH 4. A stronger base, imidazole, has been used to replace pyridine since it gives a faster response and has the advantages of lower toxicity and decreased odor. The optimal pH range for the SO2 imidazole buffer is at pH 6. It is important that the pH of the Karl Fisher reaction be maintained within the range 5 to 7. Outside this recommended pH range, the endpoint may not be reached.

There are two types of Karl Fisher titrations: volumetric and coulometric. Volumetric titration is used to determine relatively large amounts of water (1

to 100 μg) and can be performed using the single- or two-component system. Most commercially available titrators make use of the one-component titrant, which can be purchased in two strengths; 2 mg of water per milliliter of titrant and the 5 mg of water per milliliter of titrant. The choice of concentration is

dependent on the amount of water in the sample and any sample size limitations.

In both cases, the sample is typically dissolved in a methanol solution. The

iodine/SO2/pyridine (imidazole) required for the reaction is titrated into the sample solution either manually or automatically. The reaction endpoint is generally detected bivoltametrically.

Coulometric titration is used to determine relatively low concentrations of

water (10 μg to 10 mg) and requires two reagents: a catholyte and an anolyte (the generating solution). The iodine required for the reaction is generated in situ

by the anodic oxidation of iodide.

2I−→I2 + 2e−

(14.3)

The iodine then reacts with the water that is present. The amount of water titrated

is proportional to the total current (according to Faraday’s law) used in generating the iodine necessary to react with the water. One mole of iodine reacts quantitatively with 1 mol of water. As a result, 1 mg of water is equivalent to 10.71 C.

Based on this principle, the water content of the sample can be determined by

the quantity of current that flows during the electrolysis. For this reason, the coulometric method is considered an absolute technique, and no standardization

of the reagents is required.

14.2 SCOPE OF CHAPTER

The Karl Fisher instrumentation and its performance verification are discussed in this chapter. The instrumentation, calibration practices, and common difficulties that are encountered are presented. Neither method validation nor method specific problems are discussed.

14.3 INSTRUMENTATION

Karl Fisher apparatus has to be designed to exclude moisture, deliver titrant, and

to detect the endpoint. The air in the system is kept dry with a suitable desiccant, INSTRUMENTATION 223

and the titration vessel may be purged by means of a stream of dry nitrogen or

air. For endpoint detection, most commercially available units use a bivoltametric method to indicate that the endpoint has been reached. For this method a constant current of about 20 μA is applied across a pair of platinum electrodes that are about 2.5 mm apart. As the titration proceeds, water reacts with iodine and is consumed. When the endpoint is reached and all the water is consumed, there

is a buildup of free iodine in solution. The free iodine causes ionic conduction

in the solution. As a result, the voltage must be reduced to keep the polarization current constant [1,2]. When the voltage drops below a defined value, the titration

is stopped. Figure 14.1 shows a schematic diagram of a typical KF titrator.

In some cases (see below) a KF drying oven is required to get the water from

a sample into the titration vessel. For these special cases, a solid sample (usually)

is placed into a specially designed KF oven where the sample is heated, and the water goes into the vapor phase. A stream of dry carrier gas (usually, N2 or

air) sweeps the liberated moisture into the reaction vessel, where it is titrated

by either the coulometric or the volumetric method. It is critical that the carrier