Post on 26-Mar-2018
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KF-Titration
Theoretical and Practical Hints
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Topics
The Karl-Fischer ReactionChemical conditions and beside reactionsPraktical workOptimizing parametersApplication and HandlingQuality Control for a KF-Titrator
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Chemical reaction (1)
KF Titration, typical titration method with it´s three parts of definition:
Based on a stoechiometric chemical reactionKarl-Fischer reactionThere is stable reagent which can be dosed exactKarl-Fischer ReagentDosed with the Burette of the TitratorThere is an indication of the end of the reactionDouble Pt-Electrode, Biamperometric detection, Titration curve, Drift
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Chemical reaction (2)
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Chemical reaction (3)
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Chemical Conditions and Beside Reactions (1)
Check and adjust pH-value
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Chemical Conditions and Beside Reactions (2)
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Chemical Conditions and Beside Reactions (3)
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Chemical Conditions and Beside Reactions (4)
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Practical Work (1)
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Practical Work (2)
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Practical Work (3)
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Optimizing Parameters (1)
KF titration current curve
0
5
10
15
20
25
0 1 2 3 4 5
Titration agent [ml]
Stro
m [µ
A]
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Optimizing Parameters (2)
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Optimizing Parameters (3)
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Application and Handling (1)
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Application and Handling (2)
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Application and Handling (3)
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Optimizing Parameters (4)
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Application and Handling (4)
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Application and Handling (5)
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Application and Handling (6)
SeptumNeedle
Cover
Plug
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Application and Handling (7)
Liquid samples add with syringeSolid sample add directlyUse higher temperatures for better sample solubilityand faster titrationExternal ExtractionUse of an oven for gas extraction of the moisture
Overview Sample Handling Possibilities
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Validation and Quality Control (1)
Titration analysis methodsChemical reaction Reagent and dosage Indication
• Applicability • Titer stability of the titration agent • Sensor functions according to specifica-tions
• Stoichiometry • Accurate dosability with accuratevolumes of the burette
• Sensor is suitable for the indication of thechemical transformation (selectivity, sensi-tivity)
• Reaction speed • Accurately known compositionand contents of the reagent
• End of the chemical reaction
• Side reactions • Equivalent transformation can be read off orcalculated from the curve
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Validation and Quality Control (2)
Chemical reaction Reagent and dosage Indication
Reagent • Research andpublication
• Ensures composition
Manufact. • Patents • Ensures durabilityDevice • Experience • Ensures accurate dosing • Ensures indication function
• Applications • Declaration of conformity • Declaration of conformityManufac-
turer• Manufacturer’s test certificate • Manufacturer’s test certificate
User • Validation • Titer determination • Curve analysis
• Inspection of testing means • Inspection of testing means
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Validation and Quality Control (3)
Table 4: Visual inspectionDisplay Check segments: completeness, brightness, uniformity; check special charactersPlug connec-tions
Corrosion, solidity, bending, completeness, damage to the plug casings
Switches + pots Corrosion, smooth running, latching and end positions, mechanical stability,inscriptions
Casing Damage, impaired functionCylinder, piston Damage, wear and tear, dull glass, glass surfaces (interior and exterior)Piston rod Corrosion, damageSeals Liquid leakage, cracks, deformationHoses Bends, damage, connection / threading, liquid leakage, air intakeInternal structure General conditionPrinted boards Damage, in particular corrosion of the printed circuits, the components, the soldered
points, the plugsFunctioning -mechanicalsystem
Corrosion of and damage to the driving system, especially the spindle, play of the me-chanical system
Manufactures Checks 1
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Validation and Quality Control (4)
Manufactures Checks 2Table 8: Additionally with QA inspectionsCertificate A quality certificate according to DIN 55350-18-4.2.2 is issued. This document can be
used in quality management systems according to DIN EN ISO 9000 ff. The certificatemust only be issued by persons being nominated by the management and the qualitymanagement department.
Spindle travel To be measured in three points using an altimeter: 10 %, 50 %, 100 %,variance comparison
Spindle force Measurement of the maximum in a force-sensing device
pH/mV ranges Variance comparison of the measurement deviation in 3 points each
Temperaturerange
as pH/mV range
Dead-Stop range as pH/mV range
Volume accordingDIN
Weighing with water according to DIN 12 650, Part 5, at 10 %, 50 %, 100 %,variance comparison
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Validation and Quality Control (5)
Checks of user (Performance Qualification)
Sensor System(Double Pt-Electrode)
• Remove electrode from vessel• Start method• Connect both Pt-pins with a copper paper clip• Method stops after delay time (e.g. 10 sec)
Dosing System Overview:• Dose a fix volume (e.g. 10 ml) into a small calibrated
glass cylinder• Check the volume
Complete Titrator • Take Standard e.g. 5 mg water/g• 5 titrations with 0.5 , 1.0, 1.5, 2.5, 3.0 g• Calculate mean value of every weight• Calculate line with regression parameter (EXCEL) ->
Linearity
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Definition of validation
Validation and Quality Control (6)
The sounding of the term might imply truth. This would mean that“validation” would be supposed to ensure the veracity of an analy-sis result. However, Latin “validere” means “to correspond”, andthis leads to the logic, official definition, DIN EN ISO 8402:“Confirmation on the basis of an investigation and bythe provision of an objective proof of the fact that thespecial requirements imposed on a particular, intendeduse are met".Proof: provable information based on facts gathered byway of observation, measurement, a test, or in a similarform.
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Validation and Quality Control (7)
Validation feature Importance Significance for titrationAccuracy ++ the strong point of titration
Trueness ++ to be evidenced for each method
Recovery + as a rule, no sample preparation is necessary
Linearity + titration is a method with a high degree of linearity. The con-centration range being used should have been verified.
Selectivity o usually of no importanceRobustness ++ importance for the applicability to other methodsDetection limit o usually omittedDetermination limit o The range in which samples occur is defined and checked. As
a rule, however, the sample is adapted to achieve an uniformconsumption.
Validation Elements
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Validation and Quality Control (8)
Titrations with a sample as exact as possibleRepeat the titration from 5 to 10 timesCalculate mean value, SD and RSDCompare with requirements
Accuracy
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Validation and Quality Control (9)
Add water or standard to sampleModify temperatureWork with ovenModify chemical conditions like solventsTitrations with a standard as exact as possibleRepeat the titration from 5 to 10 timesCalculate mean value, SD and RSDCompare with requirements
Trueness
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Validation and Quality Control (10)
Titrations with a sample as exact as possibleAdd to the sample a defined amount of water or standardCheck, whether the standard or water was found 100%Repeat 5 timesCalculate Mean, SD, RSDCheck linearity and zero pointCompare with requirements
Recovery
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Validation and Quality Control (11)
• Take Standard e.g. 5 mg water/g • 5 titrations with every 0.5 , 1.0, 1.5, 2.5, 3.0 g • Or: Take 10 titration covering the required range • Calculate mean value of every weight • Calculate line with regression parameter (EXCEL) -> Linearity • This procedure includes Accuracy, Trueness
Linearity
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Validation and Quality Control (12)
Linearity Example
Linearitätsverhalten der Titrationsmethode
0
2
4
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10
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18
20
0 2 4 6 8 10 12 14 16 18 20 22
Sollwert [ml]
Verb
rauc
h [m
l]
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Validation and Quality Control (13)
Selectivity
Check of besides reactionsReactions, which need waterReactions, which produce water Close to recovery testCheck graphic and drift valueCompare with requirements
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Validation and Quality Control (14)
Check of titration CurveParallel to x-axis
Not too sharp bend
Good slope for good speed, continuesly
Useful volumey-axis:
consumtion in ml
x-axis: time in sec
Short titration time
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Validation and Quality Control (15)
Robustness
Tests in different laboraties with different users and titratorsCheck a list of relevant parameters:- Temperature- Reagents- Sample amount- Solvents- Titration parameters- ........
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Validation and Quality Control (17)
Detection Limit
Is not necessary for quantitative methods
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Validation and Quality Control (18)
Determination Limit
Is the smallest sample amount for a testCan be optained from the Linearity testDepends on the smallest sample amount, which can be titrated with a defined RSD
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Validation and Quality Control (19)
Determination Limit ExampleStandardabweichung in Abhängigkeit vom Verbrauch
0
1
2
3
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6
0 2 4 6 8 10 12 14 16 18 20 22
Sollwert [ml]
Stan
dard
abw
eich
ung
[%]
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Validation and Quality Control (20)
What is necessary when?
Check When?
Visual check Daily or weekly
Titre determination Weekly
Electrode and emplifier Every month
Dosing accuracy Every 6 month
Complete device Every year