KF-Titration - Innovative · PDF file\The Karl-Fischer Reaction ... KF Titration, typical titration method with it´s three parts of definition: \Based on a stoechiometric chemical

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KF-Titration

Theoretical and Practical Hints


Topics

The Karl-Fischer ReactionChemical conditions and beside reactionsPraktical workOptimizing parametersApplication and HandlingQuality Control for a KF-Titrator


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






Chemical Conditions and Beside Reactions (1)

Check and adjust pH-value








Practical Work (1)


Practical Work (2)


Practical Work (3)


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]






Application and Handling (1)













SeptumNeedle

Cover

Plug



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


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



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



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



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



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


Definition of validation


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.



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



Titrations with a sample as exact as possibleRepeat the titration from 5 to 10 timesCalculate mean value, SD and RSDCompare with requirements

Accuracy



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



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



• 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



Linearity Example

Linearitätsverhalten der Titrationsmethode

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4

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16

18

20

0 2 4 6 8 10 12 14 16 18 20 22

Sollwert [ml]

Verb

rauc

h [m

l]



Selectivity

Check of besides reactionsReactions, which need waterReactions, which produce water Close to recovery testCheck graphic and drift valueCompare with requirements



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



Robustness

Tests in different laboraties with different users and titratorsCheck a list of relevant parameters:- Temperature- Reagents- Sample amount- Solvents- Titration parameters- ........



Detection Limit

Is not necessary for quantitative methods



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



Determination Limit ExampleStandardabweichung in Abhängigkeit vom Verbrauch

0

1

2

3

4

5

6

0 2 4 6 8 10 12 14 16 18 20 22

Sollwert [ml]

Stan

dard

abw

eich

ung

[%]



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

Documents

KF-Titration - Innovative · PDF file\The Karl-Fischer Reaction ... KF Titration, typical titration method with it´s three parts of definition: \Based on a stoechiometric chemical