The document discusses Karl Fischer titration (KFT) techniques for determining water content. It describes two common methods - volumetric KFT, which uses a burette to dispense Karl Fischer reagent, and coulometric titration, which generates iodine electrochemically. The key reaction involves iodine oxidizing an intermediate alkylsulfite to alkylsulfate, consuming water. Factors like solvent choice, water content, pH, and kinetics are discussed. The document also outlines how volumetric and coulometric titrators function and how the endpoint is detected.
Karl fischer titration is an analytic system to determine the trace amount of water in solid, gases and liquids. It is a very efficient and accurate technique. In this presentation we go deeper about this titration system.
Karl fischer titration is an analytic system to determine the trace amount of water in solid, gases and liquids. It is a very efficient and accurate technique. In this presentation we go deeper about this titration system.
Notes* for the subject 'Advanced Pharmaceutical Analysis'Sanathoiba Singha
As per the syllabus prescribed by Rajiv Gandhi University of Health Sciences, Karnataka, for M. Pharm (Pharmaceutical Analysis) 1st semester.
*not all topics have been included in this collection of notes.
In this slide contains Study of Quality of Raw Materials and General methods of analysis of Raw materials used in cosmetic manufacture as per BSI
Presented by: P.PAVAN KALYAN (Department of pharmaceutical analysis).RIPER, anantapur
As we all know chromatographic fingerprinting of botanicals is a quite recent concept. This presentation will help to the beginners to understand basic thories and fundamantals of thin layer chomatography. The presentation will also provide basic experiemental understanding to perfrom HPTLC fingerprinting of samples/extracts/formulations.
Unit 6 Water Content Determination and Moisture analysisMalou Mojares
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.
Water Content Vs. Loss On Drying Of Drug In Pharma Company Part-2harish pandey
Water Content of Drug?
Impact Of Water Content Of Drug.
Methods Of Determining Water Content Of Drug.
Formula for Water Content Determination.
Calculation With Lab Practical Demo.
Loss On Drying of Drug?
Impact Of LOD Of Drug.
Formula of LOD Determination.
Calculation With Lab Practical Demo.
Basic Difference.
Analytical method validation as per ich and usp shreyas B R
Analytical method validation is a process of documenting/ proving that an analytical method provides analytical data acceptable for the intended use.After the development of an analytical procedure, it is must important to assure that the procedure will consistently produce the intended a precise result with high degree of accuracy. The method should give a specific result that may not be affected by external matters. This creates a requirement to validate the analytical procedures. The validation procedures consists of some characteristics parameters that makes the method acceptable with addition of statistical tools.
Notes* for the subject 'Advanced Pharmaceutical Analysis'Sanathoiba Singha
As per the syllabus prescribed by Rajiv Gandhi University of Health Sciences, Karnataka, for M. Pharm (Pharmaceutical Analysis) 1st semester.
*not all topics have been included in this collection of notes.
In this slide contains Study of Quality of Raw Materials and General methods of analysis of Raw materials used in cosmetic manufacture as per BSI
Presented by: P.PAVAN KALYAN (Department of pharmaceutical analysis).RIPER, anantapur
As we all know chromatographic fingerprinting of botanicals is a quite recent concept. This presentation will help to the beginners to understand basic thories and fundamantals of thin layer chomatography. The presentation will also provide basic experiemental understanding to perfrom HPTLC fingerprinting of samples/extracts/formulations.
Unit 6 Water Content Determination and Moisture analysisMalou Mojares
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.
Water Content Vs. Loss On Drying Of Drug In Pharma Company Part-2harish pandey
Water Content of Drug?
Impact Of Water Content Of Drug.
Methods Of Determining Water Content Of Drug.
Formula for Water Content Determination.
Calculation With Lab Practical Demo.
Loss On Drying of Drug?
Impact Of LOD Of Drug.
Formula of LOD Determination.
Calculation With Lab Practical Demo.
Basic Difference.
Analytical method validation as per ich and usp shreyas B R
Analytical method validation is a process of documenting/ proving that an analytical method provides analytical data acceptable for the intended use.After the development of an analytical procedure, it is must important to assure that the procedure will consistently produce the intended a precise result with high degree of accuracy. The method should give a specific result that may not be affected by external matters. This creates a requirement to validate the analytical procedures. The validation procedures consists of some characteristics parameters that makes the method acceptable with addition of statistical tools.
CHE235L4Spring2017.pdf
FW
(g/mol)
mp (
o
C) bp (
o
C) mmol mass (g)
density
(g/mL)
volume
(mL)
N/A
N/A
bismuth(III) nitrate pentahydrate N/A N/A N/A N/A
sodium chloride, saturated (brine) N/A N/A N/A N/A N/A
ethyl acetate N/A N/A
cis -1,2-cyclohexanediol N/A N/A N/A
trans -1,2-cyclohexanediol, (±) N/A N/A N/A
Prelab 4: Green Lewis Acid-Catalyzed Hydrolysis of Cyclohexene Oxide
Name:
Reaction equation:
Note: For those reagents that are in solution, the FW, mmol, and mass columns refer to the solute in the
solution.
Limiting reagent:
Reagent Table
water
Theoretical yield:
Chemical
cyclohexene oxide
EXPERIMENT #4
GREEN LEWIS ACID-CATALYZED HYDROLYSIS OF CYCLOHEXENE OXIDE
Introduction:
Epoxides are three-membered ethers. They are special because unlike most ethers, they can react
with nucleophiles to form a new bond between carbon and the nucleophile and break a bond
between that carbon and oxygen. This ring-opening reaction makes epoxides versatile functional
groups for organic synthesis. (In fact epoxide is the functional group that makes epoxy resins
possible.)
Scheme 1. Ring opening of an epoxide in the presence of a nucleophile.
Ring-opening of the epoxide can occur under basic or acidic conditions. Under basic conditions,
the reaction is similar to an SN2 reaction so that the nucleophile attacks the less substituted carbon
of an unsymmetrical epoxide by backside attack. Sodium ethoxide reacts with this epoxide in the
following reaction.
Scheme 2. Ring opening of an unsymmetrical epoxide under basic conditions.
Under acidic conditions, the reaction is more complicated. It is similar to an SN2 reaction because
the nucleophile reacts by backside attack. However, because there is partial positive charge on the
Reference Material:
MAHHS Chapter 1: Safety in the Laboratory
MAHHS Chapter 2: Protecting the Environment
MAHHS Chapter 3: Laboratory Notebooks and Prelaboratory Information
MAHHS Chapter 4: Laboratory Glassware
MAHHS Chapter 5: Measurements and Transferring Reagents
MAHHS Chapter 10: Filtration
MAHHS Chapter 11: Extraction
MAHHS Chapter 12: Drying Organic Liquids and Recovering Reaction Products
MAHHS Chapter 17: Thin-Layer Chromatography, especially section 17.8
MAHHS Chapter 20: Infrared Spectroscopy
Klein Chapter 14: Ethers and Epoxides; Thiols and Sulfides
three atoms of the epoxide ring, the nucleophile attacks where the partial positive charge is more
stabilized, the more substituted carbon of an unsymmetrical epoxide. Ethanol in the presence of
sulfuric acid reacts with this epoxide in the following reaction.
Scheme 3. Ring opening of an unsymmetrical epoxide under acidic conditions.
While sulfuric acid is an inexpensive acid catalyst, it is difficult to handle. It is very corrosive and
can cause severe burns. In addition, it is viscous, which makes it difficult to handle on the scale of
the reactions perfor ...
RAPID IODINATION OF THE ISOMERS OF AMINOBENZOIC ACID IN AQUEOUS MEDIUM BY IOD...EDITOR IJCRCPS
The rapid kinetics of the iodination of para-aminobenzoic acid and meta-aminobenzoic acid by iodine monochloride at 4.5 pH has
been studied by employing hydrodynamic voltammetry. The reactions were found to be of the second order and the specific
reaction rates for the two reactions were found to be 25 M-1s-1 and 10 M-1s-1 at 25.00C respectively. These data were
complemented with those for the iodination of ortho-aminobenzoic acid by ICl obtained earlier to quantitatively assess the relative
reactivity of the three isomers stemming from substituent regiospecificity.
Keywords: Iodine monochloride, hydrodynamic voltammetry, aminobenzoic acid isomers.
Higher Education and Research in BrazilSajjad Ullah
This presentation highlight the education system of Brasil and the opportunities of Higher Education/Research in Brazil.
Major Brazilian Funding agencies and the scholarship opportunities they offer are highlighted.
Optical band gap measurement by diffuse reflectance spectroscopy (drs)Sajjad Ullah
Introduction to Optical band gap measurement
by electronic spectroscopy and diffuse reflectance spectroscopy (DRS) with comparison of the results obtained suing different equation and measurement techniques.
The role of scattering in extinction of light as it passes through media is briefly discussed.
Introduction to Activation analysis using Neutron
Baisc Principle of NAA
Instrumental NAA
Characteristics of INAA
Advantages, Limitation and Applications of INNA
These slides briefly introduce the concepts of Radio-chemistry including nuclear stability, half life, nuclear emissions and their detection, and then highlight 02 radio chemical methods namely isotopic dilution methods and radio-chemical titrations.
How to Create Map Views in the Odoo 17 ERPCeline George
The map views are useful for providing a geographical representation of data. They allow users to visualize and analyze the data in a more intuitive manner.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
The Art Pastor's Guide to Sabbath | Steve ThomasonSteve Thomason
What is the purpose of the Sabbath Law in the Torah. It is interesting to compare how the context of the law shifts from Exodus to Deuteronomy. Who gets to rest, and why?
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
4. Determination of water content is
important
Two Methods
A – Drying methods (drying ovens,
infrared lamps and infrared balances).
B –Titration methods : Specific to water
and rapid.
Dr. Sajjad Ullah, ICS UoP
5. KFT methods
Two Methods: based on I2-providing principles
A – Volumetric KFT: I2 required for reaction is added from a
burette and water is quantified based on volume of KFR.
B – Coulometric titration methods : I2 is produced by
electrolysis of I- ions and the quantity of electricity used in
electrolysis is measured.
Advantages: High Water content (100 ppm to 100%.)
Disadvantages: Expensive, lengthy, KFR calibration
Advantages: Cheap, fast, absoulte method
Disadvantages: Low water content Water range 1 ppm to 5%
Dr. Sajjad Ullah, ICS UoP
6. How does a Volumetric Titrator work?
The volumetric titrator performs the following three key functions:
1) It dispenses KF titrating reagent containing iodine into the cell
using the burette
2) It detects the endpoint of the titration using the double platinum
pin indicator electrode
3) It calculates the end result based on the volume of KF reagent
dispensed using the onboard microprocessor.
Dr. Sajjad Ullah, ICS UoP
7. How does a Coulometric Titrator work?
The Coulometric titrator performs the following three key functions:
1) It generates iodine at the anode of the titration
cell, instead of dispensing KF reagent as in
volumetric titration.
2) It detects the endpoint of the titration using the
double platinum pin indicator electrode.
3) It calculates the end result based on the total
charge passed (Q), in Coulombs, using the on-
board microprocessor.
Dr. Sajjad Ullah, ICS UoP
8. Volumetric KFT
Principle-The titrimetric determination of water is
based upon the quantitative reaction of water with an a
solution of excess sulfur dioxide and known iodine
concentration (mg H2O/mL KFR) in a suitable medium
(methanol) in the presence of a base (buffering agent)
that reacts with hydrogen ions. The water content is
determined by measuring the amount of iodine
consumed as a result of reaction with water in a sample.
Dr. Sajjad Ullah, ICS UoP
10. The Story of KFT Reaction
Bunson Reaction:
This reaction can be used to determine H2O if SO2 is in excess
and H2SO4 is neutralized by a base. Karl Fisher did that.
Karl Fischer , Angew. Chem. 48 (1935) 394 – 396.
Dr. Sajjad Ullah, ICS UoP
11. Smith, Bryant and Mitchell Showed that:
The molar ratios were:
In a first partial reaction water forms the (hypothetical) pyridine
sulfur trioxide, which then further reacts with methanol
Dr. Sajjad Ullah, ICS UoP
12. Verhoef and Barendrecht noted that in the KF reagent it is
not the SO2 that functions as the reactive component, but rather
the intermediate monomethyl sulfite ion that is formed from SO2
and methanol:
this intermediate alkylsulfite salt is then oxidized by iodine to an
alkylsulfate salt. The reaction consumes H2O.
hydroiodic acid salt
alkylsulfite salt
alkylsulfate saltalkylsulfite salt
buffer
Verhoef, J. C. and Barendrecht, E. Mechanism and Reaction Rate of the
Karl-Fischer Titration Reaction. J. Electroanal. Chem. 1976, 71, 305-315
Dr. Sajjad Ullah, ICS UoP
13. Karl Fischer , Angew. Chem. 48 (1935) 394 – 396.
KF Reagent
A solution of iodine and sulfur dioxide
in a mixture of pyridine and methanol.
Dr. Sajjad Ullah, ICS UoP
14. hydroiodic acid salt
alkylsulfite salt
alkylsulfate salt
alkylsulfite salt
this intermediate alkylsulfite salt is then oxidized by iodine to an alkylsulfate salt.
The reaction consumes H2O.
Dr. Sajjad Ullah, ICS UoP
29. Coulometric KFT
In coulometric Karl Fischer, iodine is generated
electrochemically in situ during the titration. Water is
quantified on the basis of the total charge passed (Q), as
measured by current (amperes) and time (seconds),
according to the following relationship:
Q = 1C (coulomb) = 1A x 1S
Where 1mg H2O= 10.72 C
Dr. Sajjad Ullah, ICS UoP
30. Additional Details of the Technique
Effect of pH
Influence of Water Content
Influence of the organic solvent
Kinetics of KF reaction
Sample Size
Dr. Sajjad Ullah, ICS UoP
31. Influence of Water content
The water content of the working medium
influences the stoichiometry of the KF reaction.
High water content (aqueous media):
If H2O content > 1mol/L (18 g/L) then the reaction
behavior changes to favour the Bunsen reaction for
aqueous solutions. This means that two H2O are
consumed for one I2 or one SO2.
Dr. Sajjad Ullah, ICS UoP
32. Protic Solvent (methanol or ethanol): H2O : I2 = 1:1
Reason: reactivity of alcohols plays a role— In methanol about
100%, in propanol approx. 80% and in butanol only approx. 50%
is present as sulfite ester.
Influence of Organic Solvent
Aprotic Solvent (DMF): H2O : I2 = 2:1
Long chain alcohols: intermediate values (fractional values)
Dr. Sajjad Ullah, ICS UoP
33. Choice of Organic Solvent
A best solvent is one that assures Stoichiometry of KF reaction
and dissolve both Reactant and product of the reaction.
Methanol-the first natural choice:
Known stoichiometry, rapid reaction, Good solubilty of most samples but side reactions may occur
2-methoxyethanol (ethylene glycol monomethyl ether):
Suitbale for aldehydes and Ketones samples little side reactions (esterification, acetal/ketal formation) occur
Long-chain alcohols (ethanol, propanol)
Better solubilizing agents than methanol for lipophilic molecules
Chloroform :
good solvent for solubilizing fats and can be used with methanol. The methanol content should comprise at
least 25 % of the total volume, preferably 50 %. 100 chloroform changes the stoichiometry of KF Reaction.
Formamide (for Proteins):
improves the solubility of polar substances and can be mixed with methanol (70% methanol) for the
determination of water in proteins.
Dr. Sajjad Ullah, ICS UoP
34. Kinetics of the KF reaction
Cedergren investigated the KF reaction sequence and establish that
the reaction rate increases as the concentrations of SO2, I2
and H2O increase.
The reaction is first order referring to each individual
component.
For the rate constant K he used the equation :
And obtained the values
Dr. Sajjad Ullah, ICS UoP
35. Verhoef and Barendrecht confirmed the results of Cedergren but at
the same time found that the reaction constant K depends on the pH
of the solution:
pH < 5 log K increases linearly with the pH.
pH = 5.5 -8 the reaction rate is constant
pH > 8 the reaction rate again increases slightly
(side reactions probably occur).
Important:
From the increases in K under acidic conditions the authors conclude
that it is not SO2, but the sulfite base that is the reactive component.
Kinetics of the KF reaction…
Verhoef, J. C. and Barendrecht, E. Mechanism and Reaction Rate of the
Karl-Fischer Titration Reaction. J. Electroanal. Chem. 1976, 71, 305-315Dr. Sajjad Ullah, ICS UoP
36. The rate of the reaction depends on the pH value of the solvent, or working
medium.
at pH = 5-8 the titration proceeds normally (OPTIMAL)
at pH< 5 the titration speed is very slow
at pH> 8 the titration speed is fast (side reaction-esterification-
produces water, diffuse end point.
Comments:
Highly acidic or basic samples need to be buffered to bring the overall
pH into that optimal (5-8) range.
Effect of pH
Verhoef, J. C. and Barendrecht, E. Mechanism and Reaction Rate of the
Karl-Fischer Titration Reaction. J. Electroanal. Chem. 1976, 71, 305-315
Dr. Sajjad Ullah, ICS UoP
39. How can Titrator performance be monitored?
Dr. Sajjad Ullah, ICS UoP
40. General Considerations
Changing the molecular sieves every 6 weeks is appropriate
in the presence of medium humidity.
Molecular sieve can be regenerated at 300 degree C for 24h.
Clean the platinum pins on the indicator electrode with a soft
paper tissue, scrub softly with toothpaste. Afterwards, flush it
with ethanol or methanol.
If drift vlaues is very high during pre-titration (conditioning),
change the molecualr sives, check leakge, ensure no side reaction
or pH change has occured and the sample is soluble in solvent.
The cell solution should be replaced after approximately 30 mL of
titrant have been used in the case of cell solutions with 20...25
mL of solvent
Dr. Sajjad Ullah, ICS UoP
41. How to recognize a side reaction?
The following characteristics indicate the presence of a side reaction:
High drift after the titration has been completed, slow
endpoint recognition or no endpoint found at all
The water contents determined are not independent of the
sample weight
The results are (depending on the type of side reaction) too
high or too low
The water recovery rate found when spiking samples is not
within 100 ±3%
Dr. Sajjad Ullah, ICS UoP
48. In addition to a predefined voltage (or current), a certain drift value must also be
achieved. The drift is the amount of KF reagent per unit time that is consumed to keep
the titration cell dry. In general, the drift value for titration cells titrated to dryness is in
the order of a few μL/min.
2
49. 3. Rate of Reagent additon
The Titrant additon rate depends on
the distance from the end point―the
closer the End Point, the slower the
addition rate
the Potential change with each additon
50. The Delay time
The Titraion is terminated when E remains below the end point for
a defined time (e.g 15 seconds) following the addition of a titrant
increment
51. Titration Termination
The titration is terminated when the conditions of the Termination Criteria have
been met. The default Termination Criterion is mV value, in which the titration is
terminated after the mV value remains below the end point potential for the
selected stability time.
52.
53.
54. Additional Details of the Technique
Effect of pH
Influence of Water Content
Influence of the organic solvent
Kinetics of KF reaction
Sample Size
55. Influence of Water content
The water content of the working medium
influences the stoichiometry of the KF reaction.
High water content (aqueous media):
If H2O content > 1mol/L (18 g/L) then the reaction
behavior changes to favour the Bunsen reaction for
aqueous solutions. This means that two H2O are
consumed for one I2 or one SO2.
56. Protic Solvent (methanol or ethanol): H2O : I2 = 1:1
Reason: reactivity of alcohols plays a role— In methanol about
100%, in propanol approx. 80% and in butanol only approx. 50%
is present as sulfite ester.
Influence of Organic Solvent
Aprotic Solvent (DMF): H2O : I2 = 2:1
Long chain alcohols: intermediate values (fractional values)
57. Choice of Organic Solvent
A best solvent is one that assures Stoichiometry of KF reaction
and dissolve both Reactant and product of the reaction.
Methanol-the first natural choice:
Known stoichiometry, rapid reaction, Good solubilty of most samples but side reactions may occur
2-methoxyethanol (ethylene glycol monomethyl ether):
Suitbale for aldehydes and Ketones samples little side reactions (esterification, acetal/ketal formation) occur
Long-chain alcohols (ethanol, propanol)
Better solubilizing agents than methanol for lipophilic molecules
Chloroform :
good solvent for solubilizing fats and can be used with methanol. The methanol content should comprise at least 25 % of the total
volume, preferably 50 %. 100 chloroform changes the stoichiometry of KF Reaction.
Formamide (for Proteins):
improves the solubility of polar substances and can be mixed with methanol (70% methanol) for the determination of water in
proteins.
58. Kinetics of the KF reaction
Cedergren investigated the KF reaction sequence and establish that
the reaction rate increases as the concentrations of SO2, I2
and H2O increase.
The reaction is first order referring to each individual
component.
For the rate constant K he used the equation :
And obtained the values
59. Verhoef and Barendrecht confirmed the results of Cedergren but at
the same time found that the reaction constant K depends on the pH
of the solution:
pH < 5 log K increases linearly with the pH.
pH = 5.5 -8 the reaction rate is constant
pH > 8 the reaction rate again increases slightly
(side reactions probably occur).
Important:
From the increases in K under acidic conditions the authors conclude
that it is not SO2, but the sulfite base that is the reactive component.
Kinetics of the KF reaction…
Verhoef, J. C. and Barendrecht, E. Mechanism and Reaction Rate of the Karl-Fischer
Titration Reaction. J. Electroanal. Chem. 1976, 71, 305-315
60. The rate of the reaction depends on the pH value of the solvent, or working
medium.
at pH = 5-8 the titration proceeds normally (OPTIMAL)
at pH< 5 the titration speed is very slow
at pH> 8 the titration speed is fast (side reaction-esterification-
produces water, diffuse end point.
Comments:
Highly acidic or basic samples need to be buffered to bring the overall
pH into that optimal (5-8) range.
Effect of pH
Verhoef, J. C. and Barendrecht, E. Mechanism and Reaction Rate of the Karl-Fischer
Titration Reaction. J. Electroanal. Chem. 1976, 71, 305-315
64. General Considerations
Changing the molecular sieves every 6 weeks is appropriate
in the presence of medium humidity.
Molecular sieve can be regenerated at 300 degree C for 24h.
Clean the platinum pins on the indicator electrode with a soft
paper tissue, scrub softly with toothpaste. Afterwards, flush it
with ethanol or methanol.
If drift vlaues is very high during pre-titration (conditioning),
change the molecualr sives, check leakge, ensure no side reaction
or pH change has occured and the sample is soluble in solvent.
The cell solution should be replaced after approximately 30 mL of
titrant have been used in the case of cell solutions with 20...25
mL of solvent
65. How to recognize a side reaction?
The following characteristics indicate the presence of a side reaction:
High drift after the titration has been completed, slow endpoint
recognition or no endpoint found at all
The water contents determined are not independent of the
sample weight
The results are (depending on the type of side reaction) too
high or too low
The water recovery rate found when spiking samples is not
within 100 ±3%