To my CEU Senior Pharmacy QC 2 students. Water Content Determination by Karl Fischer method, principle by Bunsen Reaction, types of KF method, Loss on Drying (LOD) moisture content determination.

1. CHAPTER 6
WATER / MOISTURE CONTENT
DETERMINATION
(POLAROGRAPHY)
ASST. PROF. MA. LOURDES LICSI -MOJARES, R. PH.
SCHOOL OF PHARMACY
CEU MANILA

2. KARL FISCHER TITRATION
METHOD
A WIDELY USED METHOD FOR THE
QUANTITATIVE ANALYSIS OF WATER
CONTENT IN A VARIETY OF PRODUCTS.
IT USES COULOMETRIC OR VOLUMETRIC
TITRATION TO DETERMINE TRACE WATER
AMOUNTS OF IN A SAMPLE.

3. KARL FISCHER METHOD: PRINCIPLES
KARL FISCHER DISCOVERED THAT THIS
REACTION CAN BE MODIFIED TO BE USED
IN WATER CONTENT DETERMINATION (IN
AN AQUEOUS SYSTEM) CONTAINING AN
EXCESS OF SULFUR DIOXIDE.

4. KARL FISCHER TITRATOR

5. TITRATION
VESSEL MAGNETIC
STIRRER
PISTON
BURET
FOR
TITRANT
PISTON
BURET
FOR
SOLVENT
RESERVOI
R FOR
SOLVENT
RESERVOIR
FOR
TITRANT
GUARD TUBE
W/
DESSICANT
WASH BOTTLE
(CONC. H2SO4)
WASHBOTTLE
W/ KF
REAGENT
ELECTROMETRIC
INDICATOR
CIRCUIT
PISTON
MOTORS

6. KARL FISCHER METHOD: PRINCIPLES
IT IS BASED ON THE BUNSEN REACTION
BETWEEN IODINE AND SULFUR DIOXIDE
IN AN AQUEOUS MEDIUM.
HE USED 10 ALCOHOL (METHANOL) AS A
SOLVENT AND A BASE (PYRIDINE) AS
BUFFERING AGENT.

7. KARL FISCHER REACTION
ROH + SO2 + R’N [R’NH]SO3R + H2O + I2 +
2R’N
ALCOHOL BASE ALKYLSULFITE SALT WATER IODINE
2[R’NH]I + R[N’H] SO4R
HYDROIODIC ACID SALT ALKYLSULFATE SALT

8. BUNSEN REACTION: EXPLANATION
ALCOHOL REACTS W/ SULFUR DIOXIDE
AND A BASE TO FORM AN INERMEDIATE
ALKYLSULFITE SALT, W/C IS THEN
OXIDIZED BY IODINE TO AN
ALKYLSULFATE SALT.
THIS OXIDATION REACTION CONSUMES
WATER.

9. BUNSEN REACTION: EXPLANATION
pH RANGE OF THE BUNSEN REACTION
TAKES PLACE BETWEEN 5 TO 8.
pH LOWER THAN 5 – TITRATION IS
SLOW
pH LOWER THAN 8 – TITRATION IS FAST

10. KARL FISCHER REACTION
THE REACTIVE ALCOHOL IS TYPICALLY;
1. METHANOL
2. 2[2-ETHOXYETHOXY] ETHANOL /
DIETHYELENE GLYCOL MONOETHYL
ETHER / DEGEE
3. OTHER SUITABLE ALCOHOL

11. KF METHOD: HOW IT WORKS?
1. WATER AND IODINE ARE CONSUMED AT
1:1 RATIO (IN THE BUNSEN REACTION).
2. ONCE ALL THE WATER PRESENT IS
CONSUMED, THE PRESENCE OF EXCESS
IODINE IS DETERMINED
VOLUMETRICALLY BY THE INDICATOR
ELECTRODE OF THE TITRATOR.

12. KF METHOD: HOW IT WORKS?
3. THIS SIGNALS THE ENDPOINT OF THE
TITRATION.
3. THE AMOUNT OF WATER PRESENT IN
THE SAMPLE IS CALCULATED BASED ON
THE CONCENTRATION OF IODINE IN THE
KF TITRATING AGENT ( TITER), AND
THE KF REAGENT CONSUMED IN THE
TITRATION.

13. KF METHOD: ADVANTAGES
HIGH ACCURACY & PRECISION
SELECTIVITY FOR WATER
SMALL SAMPLE QUANTITIES REQUIRED
EASY SAMPLE PREPARATION

14. KF METHOD: ADVANTAGES
SHORT TIME OF ANALYSIS
NEARLY UNLIMITED MEASURING RANGE
SUITABILITY FOR ANALYSIS OF ALL
FORMS OF SAMPLES

15. KF METHOD: ADVANTAGES
INDEPENDENCE OF PRESENCE OF OTHER
VOLATILES
SUITABILITY FOR AUTOMATION

16. ADVANTAGE OF KF METHOD
TO LOD METHOD
LOSS ON DRYING (LOD) WILL ONLY
DETECT ANY VOLATILE SUBSTANCE.
KF METHOD IS VERY SPECIFIC FOR
WATER DETECTION.

17. KARL FISCHER TITRATION: TYPES
VOLUMETRIC KFT
IODINE IS MECHANICALLY ADDED TO THE
SOLVENT CONTAINING THE SAMPLE, BY
THE TITRATOR’S BURETTE DURING
TITRATION.
WATER IS QUANTIFIED ON THE BASIS OF
THE VOLUME OF THE KF REAGENT
CONSUMED.

18. KARL FISCHER TITRATION: TYPES
VOLUMETRIC KFT
BEST SUITED FOR DETERMINATION OF
WATER CONTENT IN THE RANGE OF 100
PPM TO 100%.

19. KARL FISCHER TITRATION: TYPES
TYPES OF VOLUMETRIC KFT REAGENT
SYSTEMS:
1. ONE-COMPONENT VOLUMETRIC KF
KNOWN AS COMBITITRANT OR A
COMPOSITE
IT CONTAINS ALL THE CHEMICALS NEEDED
FOR A KF REACTION.

20. KF REAGENTS: Volumetric &
Coulometric

21. KARL FISCHER TITRATION: TYPES
2. TWO-COMPONENT VOLUMETRIC KF
IT HAS BETTER LONG TERM STABILITY
FASTER TITRATION TIMES
MORE EXPENSIVE
LOWER SOLVENT POWER
TITRANT – CONTAINS IODINE & METHANOL
SOLVENT – CONTAIN THE OTHER KF
COMPONENTS.

22. KARL FISCHER TITRATION: TYPES
COULOMETRIC KFT
IODINE IS GENERATED
ELECTROCHEMICALLY “IN SITU” DURING
THE TITRATION.
WATER IS QUANTIFIED ON THE BASIS OF
THE TOTAL CHARGE PASSED, AS MEASURED
BY THE CURRENT AND TIME, ACCORDING
TO THE FF. RELATIONSHIP;

23. COULOMETRIC KFT equation
Q = 1 C = 1 A x 1 S
where: 1 mg H2O = 10.72 C
Q = total charge passed A= ampere
C= Coulomb S = second

24. VOLUMETRIC KF TITRATOR
: PROCEDURES
DISPENSES THE TITRATING REAGENT
(CONT’NG IODINE) INTO THE CELL, USING
THE BURETTE.
DETECTS THE ENDPOINT OF THE TITRATION
USING THE DOUBLE PLATINUM PIN
INDICATOR ELECTRODE.
CALCULATES THE END RESULT BASED ON THE
VOLUME OF THE KF REAGENT DISPENSED,
USING THE ON-BOARD MICROPROCESSOR.

25. COULOMETRIC KF TITRATOR:
PROCEDURE
GENERATES IODINE AT THE ANODE OF THE
TITRATION CELL.
DETECTS THE ENDPOINT OF THE TITRATION
USING THE DOUBLE PLATINUM PIN
INDICATOR ELECTRODE.
CALCULATES THE END RESULT BASED ON
THE CHARGE PASSED (Q) IN COULOMBS,
USING THE ON-BOARD MICROPROCESSOR.

26. KARL FISCHER TITRATION SYSTEMS
FISHER SCIENTIFIC AUTOMATIC KF
TITRIMETER SYSTEM, USA
HARVARD LTE TURBOTITRATOR, UK
HIRANUMA AQV 5 AQUACOUNTER,
JAPAN

27. KARL FISCHER TITRATION SYSTEMS
KYOTO, MKS 3P, JAPAN
METROHM 633 KF TITRATOR / 658 KF
METROPROCESSOR / 701 KF TITRINO,
CH
MITSUBISHI CA-06, JAPAN
METTLER DL 18 KF TITRATOR, CH

28. KARL FISCHER TITRATION SYSTEMS
RADIOMETER ETS 850 / MTS 855,
DK
SCHOTT TR 151 / TR 152 D

29. METTLER KF TITRATOR

30. METROHM FISHER SCIENTIFIC
KF TITRATORS

31. KYOTO and MITSUBISHI
KF TITRATORS

32. SCHOTT and RADIOMETER
KF TITRATORS

33. LOSS ON DRYING (LOD)
A CLASSIC LABORATORY METHOD OF
MEASUREMENT OF HIGH LEVEL
MOISTURE IN SOLID OR SEMISOLID
MATERIALS.
A RELATIVELY SLOW METHOD OF
ANALYSIS.

34. LOSS ON DRYING (LOD)
A SAMPLE OF THE MATERIAL IS WEIGHED,
HEATED IN AN OVEN, COOLED IN A DRY
ATMOSPHERE OF A DESSICATOR, THEN
RE-WEIGHED.
IF THE VOLATILE CONTENT OF THE SAMPLE IS
PRIMARILY WATER, THE LOD GIVES A
GOOD MEASURE OF WATER CONTENT.

35. DIGITAL MOISTURE ANALYZER:

36. IR MOISTURE ANALYZERS

37. HALOGEN MOISTURE ANALYZER

38. MOISTURE ANALYZERS: NEW and OLD