2 titration routine maintenance guide EN

Day-to-Day Routine Maintenanceof Automatic Titrators Sensor Performance Titrant Performance & Standardization... For titrators, such maintenance tasks include its installation arrangemen

Day-to-Day Routine Maintenance

of Automatic Titrators

Sensor Performance Titrant Performance & Standardization

Disclaimer

The information contained in this guide is based on the current knowledge and experience of the authors The guide represents selected, possible application examples The experiments were conducted and the resulting data evaluated in our lab with the utmost care using the instruments specified in the description of each

application The experiments were conducted and the resulting data evaluated based on our current state of knowledge.However, this guide does not absolve you from personally testing its suitability for your intended methods, instruments and purposes As the use and transfer of an application example are beyond our control,

we cannot accept responsibility therefore

When chemicals, solvents and gases are used, the general safety rules and the instructions given by the manufacturer or supplier must be observed.

n 1 Introduction

Analytical instruments need regular maintenance to ensure proper working conditions and finally correct results One part of maintenance is concerned with instrument adjustment, certification and the like Here manufacturer's service engineers are due to take actions

Another part are checks which are carried out by the users or an instrument responsible person They are performed frequently, on a daily or weekly base The purpose of these checks is mainly to show whether the instrument still performs according to expectation If deviations occur, the check outcomes indicate correction measures to the users

For titrators, such maintenance tasks include its installation arrangement, the influence of temperature, the sensor functionality, the titrant status and considerations regarding the sample size

tion 2 Instrument InstallationProfessional installation is fundamental to every analytical system Depending on the requirements, the right

level of measures needs to be applied The measures encompass the following 4 topics

GLP

International bodies have elaborated a set of rules concerning the analytical work in labs in order to achieve

a standard regulation recognized and accepted in all countries of the world These rules are commonly known

as GLP rules (Good Laboratory Practice) GLP is a formal framework for testing chemicals and consists of

10 specific rules

Certification of an automatic titrator

The certification is a check of the instrument in order to verify that the technical specifications are fulfilled,

or to verify if the actual specifications meet the required level

Certification is only part of a list of measures to guarantee correct results

Validation of Titration Methods

While the goal of the analysis is to get correct results, very often the ‘correct’ result is not necessarily the ‘true’ result As a result, our goal is in fact to get the best possible result This means a result as accurate, precise and true as possible To do this it’s important to critically investigate the factors affecting each of these things and minimize the negative influences

Qualification

Quality management requires the documentation of the performance over the lifetime of the instrument, i.e., from the project phase through manufacturing, installation and operation through disposal of the instrument All these steps are resumed in the comprehensive concept of qualification:

• Specification Qualification (SQ): Requirements, Functions, Design, HW/SW

• Construction Qualification (CQ): Production control for each product

• Design Qualification (DQ): Selection of correct instrument for intended use

• Installation Qualification (IQ): Evidence of correct installation at customer’s facility

• Operational Qualification (OQ): Evidence and compliance to specifications, SOPs, initial calibration,

user training

• Performance Qualification (PQ): Periodic performance tests

• Maintenance Qualification (MQ): Definition of preventive maintenance and calibration/certification intervals

Specially trained METTLER TOLEDO service engineers are able to perform the calibration and certification of the titrator hardware with specific calibrated and certified tools (CertiCase, Excellence Test Unit)

Recommendations

• Have the titration system installed by the instrument manufacturer’s specialist

• Perform a General System Suitability Test, proving that the titrator is performing according to the specifications

• Apply the concept of qualifications

Figure 1: Lab titrator family

ts 3 The Effects of Temperature on the Results

Temperature can have three different effects on a titration

The first effect is related to the density, and therefore the concentration of the titrant The effect is due to the coefficient of thermal expansion This is of particular significance with non-aqueous titrants where the coefficient

of thermal expansion is much higher than with deionized water Below is a table showing typical errors

The second becomes apparent when performing an endpoint titration to a predefined pH value The pH of the sample depends on the degree of dissociation of the acids and bases present The dissociation is temperature dependent Thus, a temperature change gives rise to a real change in the pH value This change cannot be accounted for without knowing the sample’s exact composition

A further effect concerns the actual measurement process and the slope of the electrode calibration curve The slope of the calibration curve is temperature dependent so it is important to either perform the analysis at the same temperature at which the electrode was adjusted, or to measure both temperatures and compensate for the change in slope of the calibration curve Fortunately, most modern instruments are able to simultaneously measure the sample temperature and automatically compensate for this error

Table 1: Error in concentration due to temperature change

Recommendations

• The best solution is to maintain constant temperature in the laboratory e.g by air condition Air condition prevents temperature shifts

• Keep samples in the same place as titrants to ensure the same termperature If the titrant concentration (i.e titer determination) and samples are measured at the same temperature then there is no error

• Do not expose the instrument to direct sunlight Place it in a protected area

• Measure the temperature when performing pH measurements or end point titrations

- METTLER TOLEDO offers pH sensors with integrated temperature probes for this purpose

• Use certified pH buffers for sensor calibration and apply their temperature table

- METTLER TOLEDO titrators and pH meters automatically offer this possibility

• Perform titrant standardization when the temperature changes significantly Re-standardizing reduces errors due to temperature changes considerably

Apply a temperature correction factor: Measure the temperature of the titrant and correct for the temperataure change

Example: Karl Fischer reagent, 10°C temperature difference in the lab

f = 1 + (Ttiter – Tsample) x CONC-ERR CON C-ERR = 0.092 / 100 = 0.00092

TT – TS = -10

f = 1 – 10 x 0.00092 = 0.9908

Multiplying raw results by this factor will account for the error

1 component 5 mg/mL Karl Fischer Reagent 0.092

e 4 Sensor Performance

In pH endpoint titrations, critical factors affecting result accuracy are the slope and zero point of the sensor Both of these parameters are used to convert the raw mV signal from the sensor into the pH of the sample solution using the Nernst equation:

, where

E = measured signal (in mV)

S = sensor slope = – 2.3 RT / nF

pH0 = sensor zero point = E0/S

Since sensors are the actual ‘measurement devices’, they have a very large influence on the result of any titration Several factors contribute to their behaviour:

Response: If a sensor is sluggish because of old age or bad maintenance, the mV reading detected by the

sensor will lag behind the ‘true’ value

Calibration: Sensor calibration is particularly important for endpoint titrations (mainly pH endpoints) The

accuracy of the measured value is directly related to the determined amount of the analyte content in the sample Every maintenance procedure performed on a sensor (cleaning, regeneration, etc.), requires that the sensor

be calibrated again

For pH, we recommend to apply a two or three point calibration If samples are usually around 7, three

calibration points at pH 4, 7 and 9 (or 10) are good practice This ensures that pH values below and above

7 are measured correctly If the samples are acidic, a two point calibration between 4 and 7 is usually

acceptable and yields reliable results

mV

pH

real

ideal

0

Figure 2: Schematic of a three-point pH calibration

Reference electrode: A reference electrode has to provide a stable reference signal against which the

measurement signal is determined

Conditioning: The measuring membrane of any pH or ion selective electrode needs to be conditioned before

the sensor can be used

pH = pHo – ES

e When a pH sensor is used in non-aqueous media, the sensor needs to be conditioned before its next use to

restore the hydration layer

Recommendations

• Define a sensor calibration frequency to make sure that the sensor is measuring correctly, e.g at least once per day

• Instead of frequent calibrations, a sensor check can be performed Such a check shows that the sensor is still functioning correctly but it does not change calibration data The sensor check should include the signal drift over one minute, which is an important indication of the response time and signal stability Use pH buffer

4 or 9 as a sample for this check

• Take the appropriate measures to automatically remind users to calibrate

- METTLER TOLEDO Excellence titrators offer the functionality of monitoring sensors’ life span as well as usable life When a calibration needs to be performed or the sensor needs replacing, the user is automatically reminded A sensor can even be blocked from use if the setting is chosen accordingly

• Define acceptance limits for the calibration results

- All METTLER TOLEDO titrators allow these limits to be set in the method If the limit is exceeded, the user is prompted and the calibration data is not saved

• When not in use, sensors should be stored in electrolyte

Figure 3: Details of the measuring membrane of pH electrodes

ce 5 Titrants Performance

The concentration of a titrant needs to be known accurately to be able to determine the content of analyte in the sample solution If the titrant concentration is unknown or inaccurate, there will inevitably be a degree of error

Titer

From the determined titrant concentration and the nominal titrant concentration, a titer value t is calculated The titer is the ratio of ‘determined concentration / nominal concentration’ and is generally close to 1

t = current titrant concentration / nominal titrant concentration

Example: Current titrant concentration, by determination: 0.1036 mol/L

Nominal titrant concentration, by declaration: 0.1 mol/L Titer t = 0.1036 / 0.1 = 1.036

For titer determinations, a primary standard is preferable A primary standard is a substance that reacts with the titrant in a known ratio ("stoichimetrically") Its purity is high and well defined It is very stable and has a high molecular weight

Examples of primary standards: Tris-hydroxy amino methane (THAM) for acids,

Potassium hydrogen phthalate (KHP) for bases, NaCl or KCl for argentometry

Titrant life time

Titrants can deteriorate over time through various external influences like oxidation, precipitation, carbon dioxide absorption or UV degradation We can account for some of these by using drying tubes filled with NaOH on carrier material (CO2 absorption in alkaline titrants) or with brown bottles (light protection)

The rate of deterioration determines how long the titrant can be used before re-standardizing This is called the “usable life’ of the titrant After the usable life has expired, a new titer determination should be performed before running subsequent analyses In most titrators, the usable life of a specific titrant can be defined and standardization intervals can be enforced before being allowed to continue

The lifespan of a titrant is the time after which a titrant should be replaced The lifespan is different for every type of titrant For example, acids are more stable than alkaline titrants and can have a life span of up to a year, compared to 6 months for a base During the lifespan, regular standardization should be performed to guarantee reliable results

Recommendations

• Define a standardization frequency ensuring titrant concentration (titer t) is correct

• Define a titrant life span

• Take the appropriate measures to automatically remind users to perform a standardization, preventing usage

of a titrant with an exceeded usable life

- METTLER TOLEDO Excellence titrators offer the functionality of monitoring titrants, automatically warn and remind users and block unfit titrants from use

• Define acceptance limits for the titer determination, e.g 0.96 ≤ t ≤ 1.05

- All METTLER TOLEDO titrators allow these limits to be set in the standardization method If the limit is exceeded, the user is prompted and the new titer value will not be saved

• Prepare and store titrants with care

ce • In the case of alkaline titrants such as sodium and potassium hydroxide, it’s important that they are prepared

with water or solvent free of carbon dioxide, and that they are protected from atmospheric exposure to carbon dioxide Attach a drying tube containing an absorbent (e.g NaOH on a granular carrier) to the titrant bottle

• Titrants such as iodine, permanganate and dichromate are light sensitive and need to be protected by storing them in brown glass bottles Karl Fischer reagents need to be protected from light as well as from the ingress

of atmospheric humidity This is done by attaching a drying tube containing silica gel or molecular sieve to the titrant bottle

Figure 4: Automatic titrator with 5 titrants (burettes)

e 6 Sample Size

By far, the biggest source of random errors resulting in precision problems is sample handling These errors include inhomogeneity of the sample, sample storage problems, incorrect sample size, weighing errors, and careless handling Critical in most cases is the sample size

The sample should be large enough to ensure that it is representative, but it shouldn’t be so large that repeated burette fillings are necessary during the titration The ideal sample size should give a titrant consumption of 30

to 80% of a single burette volume

On the other extreme, the sample should be large enough so that weighing or sample measuring errors are kept

to a minimum Here, a suitable balance must be used to ensure that the sample size exceeds the minimum weight of the balance This minimum weight is defined as the weight which when measured tenfold, results in a repeatability of less than a certain pre-defined value; for example, United States Pharmacopoeia (USP) states

a value of less than 0.1%

The sample volume including deionized water and/or other solvents that is used for any titration should be sufficient to cover the sensor’s active parts (junction and sensing membrane or metal ring) Normally, this volume should be around 50 mL to be able to fit the stirrer, titration tubes and dosing tubes in with the probe For smaller sample sizes, special micro-titration beakers can be used

Recommendations

• Make sure that you're using the needed balance resolution for your sample size The accuracy and precision

of the sample size must be smaller than the expected accuracy and precision of the titration result

• For solid samples, use a calibrated analytical balance with 0.1 mg or 0.01 mg readability

• For liquid samples use a calibrated high quality Rainin® pipette

• Choose a sample size that consumes 30 to 80% of the burette’s volume The sample size, titrant concentration

or burette size can be changed to reach this goal

• Dilute the sample with an appropriate solvent volume to make sure the active parts of the equipment are covered (approximately 50 mL) If necessary, use micro-titration equipment