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Fast and fundamental: influences on reliable electrochemical measurements

Fast and fundamental: influences on reliable electrochemical measurements

The ultimate goal of any researcher is to contribute to the progress of society by pioneering exploration beyond the known limits. Depending on the research type and application field, one way to fulfill this is to collect reliable experimental data on rapidly occurring processes (less than 1 ms).

Having insight into the fundamentals of these reaction mechanisms can ultimately lead to the discovery of new materials or the improvement of current solutions. In electrochemical research, reaction mechanisms and intermediates are investigated by measuring the kinetics and dynamics of the electrochemical processes happening at the surface of the electrode on a sub-ms timescale.

This article provides a short overview of the factors that have a direct influence on fast and ultra-fast electrochemical measurements from an experimental setup perspective.

Considering the following factors in the experimental design and execution is the first condition to obtain reliable experimental results for such measurements.

Additional challenges which researchers must be aware of when experimenting with «transient electrochemistry», i.e. doing electrochemical measurements at very low time scales, is presented in the featured article from E. Maisonhaute et al. [1].

Main factors that influence the reliability of fast electrochemical experimental results

The primary components of an electrochemical experimental setup are:

  • The electrochemical cell including the electrodes and electrolyte
  • The electrochemical instrument, i.e., the potentiostat/galvanostat (PGSTAT)

To perform reliable electrochemical experiments in general, and fast electrochemical measurements in particular, the specifications of the complete work system must be considered and the optimal settings must be used for all of the individual parts of the experimental setup.

Time constant of the electrochemical cell

The electrochemical cell and its specifications must be taken into account as it is an important element of the experimental setup.

Transient electrochemical experiments are not meaningful unless the cell time constant is small relative to the timescale of the measurement, regardless of the high-frequency characteristics of the control circuitry.

The cell time constant RuCdl (s) depends directly on the uncompensated resistance Ru (Ω) (i.e. the resistance of the electrolyte between the reference and the working electrode) and the double-layer capacitance Cdl (F) of the electrode [2].

As a consequence, when the potential is stepped or scanned rapidly, the true measured potential Etrue (V) lags behind the applied potential Eappl (V), according to the following equation:

Where RuCdl (s) is the time constant of the cell and t (s) is the time at which the measurement is taken.

Figure 1. Theoretical and true waveform applied to a real electrochemical cell [1].

For fast scan rates (i.e. when 𝑡 is much smaller than RuCdl ), the exponential term approaches 1 and significant errors in 𝐸true with respect to 𝐸appl can arise. For slow scan rates (i.e. when 𝑡 is much larger than RuCdl), the exponential approaches 0 and the errors become negligible.

The time constant of the cell can be reduced in three ways:

  • Reduce Ru via increasing the conductivity of the electrolyte by either increasing concentration of supporting electrolyte or decreasing viscosity
  • Reduce the size of the working electrode (e.g., by using microelectrodes) so that Cdl will be minimized
  • Move the reference electrode as close as possible to the working electrode (e.g., by using a Luggin capillary) so that Ru will be minimized

The electrochemical instrument: potentiostat/galvanostat (PGSTAT)

The potentiostat/galvanostat (PGSTAT) is used to accurately control the applied signal (potential or current) and measure the response (current or potential, respectively) from the electrochemical cell. The accurate control of the applied signals is achieved by using a control loop (or feedback loop) circuit.

When fast electrochemical measurements are executed, the following specifications will have a direct influence on the results and must be considered.

Bandwidth of the control loop of the PGSTAT

In general terms, bandwidth can be described as the parameter that defines how fast the instrument is able to react to any changes in the signal.

In electrochemical terms, the bandwidth is the frequency beyond which the performance of the system is degraded.

The bandwidth of the control loop of the PGSTAT (i.e. bandwidth of the instrument) indicates how fast the applied signal is controlled through the feedback loop.

Higher bandwidth means that the instrument uses a faster control loop (faster feedback). As a result, the applied signal will reach the desired set point faster, and in ideal circumstances the output signal will be identical to the theoretical waveform. However, depending on the properties of the electrochemical cell connected to the instrument, the applied signal might overshoot. In extreme cases, the instrument feedback loop might get out of control causing the potentiostat to oscillate. This is more likely when high-capacitance electrochemical cells are connected to the PGSTAT.

When a Lower bandwidth is used, the overall stability of the PGSTAT increases by reducing the speed of the control loop. In this case, the consequence is that at very high measurement speeds, the output of the applied signal may be slightly less accurate due to a slower slew rate. Nevertheless, when measuring fast transients is not within the scope of the experiment, using the instrument with a lower bandwidth setting is recommended for highly accurate experimental results.

Figure 2. Schematic representation of the applied signal when Low bandwidth (Low speed) and High bandwidth (High speed) settings are used compared with the theoretical response.

Therefore, it is important to choose the control loop bandwidth settings according to the type of the measurement. For ultra-high speed measurements, a higher bandwidth setting must be used with the following considerations:

  • The higher the bandwidth, the higher the noise and the probability that the control loop will go out of control and oscillate.
  • When working with a High bandwidth setting, it is necessary to pay special attention and use adequate cell shielding and electrode connectors. The use of a Faraday cage is recommended in these cases.
  • The use of a high impedance reference electrode (RE) (e.g., double junction reference electrode, a salt bridge with frit) in combination with a High bandwidth of the control loop might lead to instability of the PGSTAT and even to oscillations.
Bandwidth of the current sensor (current range)

The measurement of the current response of an electrochemical cell (in potentiostatic mode) and the control of the applied current value (in galvanostatic mode) is executed with specially designed current sensors. In order to achieve the best sensitivity and resolution for the measurement, individual current sensors are used depending on the magnitude of the measured (or applied) current.

Each current sensor circuit (which corresponds to a current range) has a specific bandwidth or response time. Therefore for the most accurate results (especially important for fast, time resolved experiments), the current range must be selected so that the bandwidth of the current sensor will not be the limiting factor for the time response (speed) of the measurement.

In general, the lower the measured currents, the lower the bandwidth of the current sensor.

Data sampling interval vs the timescale of the investigated transient signal

The measured electrochemical response can have a complex shape with components at many frequencies. The highest frequency component of the measured or applied signal determines the bandwidth of that signal. The bandwidth of the signal should not be higher than the bandwidth of the measuring device.

If the highest frequency component of the signal is fSIGNAL, then according to the Nyquist Theorem [3] the sampling rate fSAMPLE must be at least 2 fSIGNAL (i.e. two times higher than the highest frequency component of the signal).

Figure 3. Effect of the sampling frequency of an ideal sinusoidal signal [3]. Shown here are the theoretical signal (dashed line), sample points, and resulting measured signal (orange line).

In other words, the data sampling interval must be lower than the timescale in which the time resolved (transient) measurement from the investigated electrochemical process is expected to occur. There is a practical correlation between the sampling interval and instrument bandwidth. When the sampling interval is:

  • higher than 100 μs: the 10 kHz (High Stability) bandwidth should be selected.
  • between 10–100 μs: the 100 kHz (Fast) bandwidth should be selected.
  • smaller than 10 μs: the 1 MHz bandwidth (Ultra-Fast) should be selected.

Summary

To measure reliable experimental data, all elements of the experimental setup must be considered with their own specifications and limitations. The overview above highlights the main factors and parameters which can have a direct influence on fast electrochemical measurements.

Fast measurements start here!

Visit our website to learn more about the variety of potentiostats/galvanostats from Metrohm Autolab.

References

[1] Maisonhaute, E.; et al. Transient electrochemistry: beyond simply temporal resolution, Chem.Commun., 2016, 52, 251—263. doi:10.1039/C5CC07953E

[2] Bard, A.J.; Faulkner, L.R. Electrochemical Methods: Fundamentals and Applications, New York: Wiley, 2001, 2nd ed. Russian Journal of Electrochemistry, 2002, 38, 1364–1365. doi:10.1023/A:1021637209564

[3] Keim, R. The Nyquist–Shannon Theorem: Understanding Sampled Systems. All About Circuits, May 26, 2020. https://www.allaboutcircuits.com/technical-articles/nyquist-shannon-theorem-understanding-sampled-systems/ 

Post written by Dr. Iosif Fromondi, Product Manager and Head of Marketing and Sales Support at Metrohm Autolab, Utrecht, The Netherlands.

Nonaqueous acid-base titrations – Common mistakes and how to avoid them

Nonaqueous acid-base titrations – Common mistakes and how to avoid them

Nonaqueous acid-base titrations are widely used in several industries, including the petrochemical  and pharmaceutical sectors. Whether you are determining the acid or base number (AN or BN) in oils or fats, titrating substances that are insoluble in water, or quantifying products with different strengths of acidity or alkalinity separately, nonaqueous acid-base titration is the method of choice.

If you already have some experience performing nonaqueous acid-base titrations, you may remember that there are several challenges to overcome in comparison to aqueous acid-base titrations.

In this blog post, I would like to cover some of the most typical issues that could pop up during nonaqueous acid-base titrations and discuss how to best avoid them. An important point to note is that there is no single solution regarding how to perform any nonaqueous acid-base titration correctly. The right procedure depends highly on the solvent and titrant used.

What is a nonaqueous acid-base titration?

Before discussing nonaqueous titrations, first let’s talk a little bit about aqueous acid-base titrations.

Here, a sample is dissolved in water, and depending of the nature of the sample (whether it is acidic or basic) a titration is performed either using aqueous base or aqueous acid as titrant. For indication, a glass pH electrode is used.

However, sometimes due to the nature of the sample, aqueous titration is not possible. Nonaqueous acid-base titration is used when:

  • the substance of interest is not soluble in water
  • samples are fats or oils
  • components of mixtures of acids or bases have to be determined separately by titration

In these cases, a suitable organic solvent is used to dissolve the sample instead of water. The solvent:

  • should dissolve the sample and not react with it
  • permits the determination of components in a mixture
  • if possible, should not be toxic

The solvents that are most often used include ethanol, methanol, isopropanol, toluene, and glacial acetic acid (or a mixture of these). Titrants are not prepared with water but rather in solvent. Frequently used nonaqueous basic titrants are potassium hydroxide in isopropyl alcohol or sodium hydroxide in ethanol, and a common nonaqueous acidic titrant is perchloric acid in glacial acetic acid.

Due to the nature of nonaqueous solvents, they are normally poor conductors and do not buffer well. This makes indication a bit challenging because the electrode must be suitable for such sample types. Therefore, Metrohm offers the Solvotrode which is developed specifically for nonaqueous titrations.

This pH electrode offers the following advantages over a standard pH electrode:

  • Large membrane surface and a small membrane resistance for accurate reading, also in poorly buffered solutions
  • A flexible ground-joint diaphragm which can easily be cleaned even when contaminated with oily or sticky samples, additionally it offers a symmetrical outflow for outstanding reproducibility
  • The electrode is shielded and is therefore less sensitive to electrostatic interferences
  • It can be used with any nonaqueous electrolyte such as lithium chloride in ethanol

In the following sections I will discuss the most common mistakes when performing potentiometric nonaqueous acid-base titrations and how you can avoid them.

Electrostatic effects

The influence of electrostatic effects during analysis is normally negligible. However, maybe you have once seen a curve like the one below which looks relatively normal until suddenly a spike occurs.

Figure 1. Titration curve with a spike which might have occurred from an electrostatic interference.

This is then an indication of an electrostatic effect. However, where does it come from and how can we overcome this?

Electrostatic charge can be generated from many sources, such as friction. For example, while walking across a surface you will generate an electrostatic charge which will be stored in your body. You have probably touched the doorknob after walking across a carpeted space in your socks and obtained a small electric shock—this is the discharge of built up electrostatic charge. If we now assume that you are electrostatically charged and then you approach an electrode that is currently measuring (in use), this will result in a spike (Figure 1). Therefore, it is essential to make sure that you are either properly discharged or that you do not approach the electrode during measurement. You can avoid this issue by wearing the appropriate clothes. ESD (electrostatic discharge) clothes and shoes are mostly recommended when performing nonaqueous titrations.

Blocked diaphragm

A blocked diaphragm is another point which occurs more regularly during nonaqueous titrations. Due to the oily and sticky sample, you might have seen that the electrode diaphragm is clogged and cannot be opened anymore. What should you do then?

In most cases, you can place the electrode in a beaker of warm water overnight. This treatment often helps to loosen the diaphragm. To completely prevent the diaphragm from clogging, a Solvotrode with easyClean technology should be used. With this electrode, electrolyte is released by pressing the head ensuring that the diaphragm is not blocked.

Choice of electrolyte and storage solution

We recommend two types of electrolyte for nonaqueous titrations.

For titrations with alkaline titrants: tetraethylammonium bromide c(TEABr) = 0.4 mol/L in ethylene glycol

For titrations with acidic titrants: lithium chloride c(LiCl) = 2 mol/L in ethanol

Please make sure to store the electrode in the same electrolyte with which it is filled.

Checking the electrode according to ASTM D664

To check whether the Solvotrode is still in good working condition, perform a test according to ASTM D664 using aqueous buffer solutions of pH 4 and 7. The procedure is as follows:

  • Measure the potential of buffer pH 4.0 while stirring and note the value after 1 minute
  • Remove the electrode and rinse it well with deionized water
  • Measure the potential of buffer pH 7.0 while stirring and note the value after 1 minute
  • Calculate the mV difference between the reading of buffers 4.0 and 7.0
  • The difference must be larger than 162 mV (20–25 °C) to indicate an electrode in good shape

If the measured potential difference is less than 162 mV, the electrode requires maintenance. Lift the flexible sleeve of the ground-joint diaphragm to let some electrolyte flow out. Repeat the measurement according to the steps above. If the value is still less than 162 mV, clean the electrode or replace it.

Proper rinsing and cleaning

Proper rinsing is essential if you want to obtain reliable results. Otherwise, the curve might flatten and the equivalence points are no longer recognizable. Figure 2 illustrates this phenomenon well.

Figure 2. Different determinations according to ASTM D664. With time, the start potential of the curves shifts which indicates an unsuitable cleaning procedure.

The sample is the same, however, you see that the equivalence point and starting potential begin to shift and the curves become flatter. This indicates an improper cleaning procedure between measurements. The corresponding electrode is shown in Figure 3.

Figure 3. Appearance of the electrode used in Figure 2 after five measurements.

This electrode was certainly not cleaned properly! Anyone who performs a nonaqueous titration must consider which solvent might best dissolve the residue—this is not an issue that other analysts can easily solve due to the nature of each individual sample. However, do not ignore an electrode with such an appearance.

Conditioning the glass membrane correctly

As you may remember from our previous blog post about pH measurement, it is essential that the hydration layer of the glass membrane stays intact. Nonaqueous solvents dehydrate the glass membrane rather quickly. A change in the hydration layer can have an impact on the measured potential, therefore it is important that the hydration layer is always in the same state before starting a titration to achieve the most reproducible results.

Proper electrode immersion depth

This can be established with a conditioning step of the glass membrane to rebuild the hydration layer. However, if the solvent is able to remove the hydration layer faster than it takes to perform a titration, this can lead to ghost equivalence points. Therefore, the electrode should be completely dehydrated and kept like this for all further titrations.

 

Polar solvents (e.g., ethanol, acetone, isopropyl alcohol, or mixtures with toluene)

Water-free solvents (e.g., dimethylformamide, acetonitrile, acetic anhydride, or mixtures of these)

Preparation of electrode

Store only the pH membrane (not the diaphragm) in deionized water overnight to build up a proper hydration layer.

Lift the flexible sleeve to allow some electrolyte to flow out.

Dehydrate the pH membrane by placing only the pH membrane (not the diaphragm) in the solvent you will use afterwards for titration.

Lift the flexible sleeve to allow some electrolyte to flow out.

Conditioning of glass membrane Place the pH membrane (bulb only) into deionized water for 1 minute. Place the pH membrane (bulb only) into the corresponding solvent for 1 minute.
Rinsing procedure Rinse electrode with 50–70% ethanol. If this does not help, use a suitable solvent to rinse the electrode and then clean afterwards with 50–70% ethanol. Rinse electrode with glacial acetic acid. If this does not help, use a suitable solvent to rinse the electrode and then clean afterwards with glacial acetic acid.
Remarks Make sure to always keep the bulb of the electrode in deionized water for the same time duration, otherwise the thickness of the hydrated layer (and therefore the response) may vary. Avoid any contact of the electrode with water as this can induce a reaction with the solvent causing ghost equivalence points and irreproducible results.

Maintenance of burets

It is not only the electrode that needs some special attention when performing nonaqueous titrations, but also the electrical buret. Some special maintenance is required since alkaline nonaqueous titrants are especially aggressive and they tend to crystallize, therefore leakage of the buret is likely.

The buret must be maintained on a regular basis according to the manufacturer’s instructions. Metrohm recommends the following procedure:

  • For shorter titration breaks, it is recommended to refill the cylinder with titrant (especially with OMNIS)
  • Clean the buret with deionized water at the end of the day
  • Lubricate the cylinder unit on the centering tube and on the cylinder disc

Also check the corresponding manual of the buret. The most important points are mentioned there which will lead to a longer working life of the buret.

Thermometric titration as an alternative

One alternative to using potentiometric nonaqueous acid-base titration is thermometric titration (TET), depending on the sample and analyte to be measured. Thermometric titration monitors the endothermic or exothermic reaction of a sample with the titrant using a very sensitive thermistor.

The benefit of TET over potentiometric titration is clearly the maintenance-free sensor which does not require any conditioning nor electrolyte refilling. More information about thermometric titration can be found in our previous blog posts below.

Summary

Hopefully this article has provided you with information about the main problems encountered during nonaqueous titrations. First, make sure that all electrostatic influences are eliminated. This will save a significant amount of troubleshooting. Then prepare and treat your electrode correctly before, during, and after titration. Make sure to condition the electrode right before your first measurement!

Of special importance here is the solvent you plan to use. If it is a polar solvent, the electrode should be conditioned in deionized water. If nonpolar solvents like acetic anhydride are used, the electrode should be dehydrated first. Between measurements, the electrode should be cleaned with a suitable solvent and the diaphragm should be opened on occasion.

Last but not least, take care of your buret. Maintain it regularly and replace it whenever necessary. With this advice, performing nonaqueous titrations should be a breeze!

For more information

about nonaqueous titrations, download our monograph:

Nonaqueous titration of acids and bases with potentiometric endpoint indication

Post written by Iris Kalkman (Product Specialist Titration at Metrohm International Headquarters, Herisau, Switzerland) and Dr. Sabrina Gschwind (Head of R&D at Metroglas, Affoltern, Switzerland).

Green hydrogen, future fuel: Using potentiostats to develop new catalysts for hydrogen production

Green hydrogen, future fuel: Using potentiostats to develop new catalysts for hydrogen production

Hydrogen – clean and green?

Due to its high gravimetric energy density and zero pollution emission, «green hydrogen» is a clean and sustainable energy carrier which is expected to become one of the fuels of the future. Green hydrogen is produced with renewable energy sources, and it can help to mitigate global warming by using cleaner fuels.

Producing green hydrogen with electrolysis

The most favorable way to produce green hydrogen is via water splitting electrolysis, where water (H2O) is broken down into its counterparts by using a direct electric current. Electrolysis is a sophisticated technique that has been used for many decades in industry. When using this technique for the production of hydrogen, drawbacks are the sluggish reaction kinetics when using inexpensive catalysts or the high costs for more optimal catalysts (e.g. platinum). To produce hydrogen in an efficient and economical manner, the goal for researchers around the world is to develop catalysts for this purpose which are highly active, inexpensive, and stable over long periods.

This article explains in more detail how Metrohm potentiostats can be used to characterize recently developed catalysts for electrochemical hydrogen production.

Electrode reactions

Considering alkaline solutions, the water splitting reaction can be described by two half reactions (Figure 1):

  • Hydrogen Evolution Reaction (HER) at the cathode
  • Oxygen Evolution Reaction (OER) at the anode
Figure 1. Water splitting reaction with the respective half reactions at the cathode and anode.

A critical issue for water splitting is the slow reaction kinetics of the half reactions. To overcome this, electrocatalysts which decrease the activation energy to an acceptable value need to be designed. For an ideal catalyst, a voltage of 1.23 V (at 20 °C and 1013 mbar) would have to be applied to begin hydrogen and oxygen evolution between the electrodes. Unfortunately, when using catalysts in real life situations, voltages above 1.8 V need to be applied.

Requirements for suitable catalysts

Catalysts for the production of green hydrogen from electrochemical water splitting reactions must be (click to go directly to each segment):

The first three properties can be determined by electrochemical measuring techniques using a potentiostat.

Activity

The activity of a catalyst is characterized by three values (click to go directly to each segment):

which can be obtained from the polarization curve as displayed in Figure 2.

Figure 2. Polarization curves of an ideal catalyst (orange) and a real catalyst (dark blue) considering the Hydrogen Evolution Reaction (HER) and Oxygen Evolution Reaction (OER).
Linear polarization

To record a polarization curve (Figure 2), a potentiostat is used in combination with a three-electrode setup. The working electrode is coated with the catalyst which is to be characterized. A typical setup for this purpose is shown in Figure 3.

Figure 3. Potentiostat from Metrohm Autolab combined with a three-electrode setup using a Rotating Disc Electrode (RDE) as working electrode to keep mass transport under defined conditions.

During the measurement, the potential (beginning at a defined initial potential value) is swept to the end potential in a linear fashion over a certain time interval (Figure 4). For HER-catalysts, the potential is swept in the negative direction compared to the initial potential; catalysts used for OER purposes are swept to positive potentials with respect to the initial potential.

The overpotential (η) is a very important parameter to evaluate the activity of the catalyst; its value is affected by the kinetic barrier for the reaction. To overcome this barrier, a higher potential than the thermodynamic potential (1.23 V for OER, or 0 V for HER) – the overpotential – has to be applied to reach the same current densities. The more active the catalyst, the lower the overpotential.

Figure 4. General diagram of linear sweep voltammetry.
Tafel analysis

Aside from the overpotential, the Tafel slope and exchange current density are two additional parameters that help characterize the activity of the catalyst. They can be accessed by plotting the logarithm of the kinetic current density versus overpotential to create the so-called «Tafel plot» (Figure 5).

Figure 5. Tafel plot of OER for two different catalyst materials.

By evaluating the Tafel plot, these two important kinetic parameters can be extracted. One is the Tafel slope (b) which can be expressed by the following equation:

η = a + b log i

  • η = overpotential
  • i = current density

The other parameter is the exchange current density (i0), which can be obtained by extrapolating the current at zero overpotential (Figure 6).   

The Tafel slope is related to the catalytic reaction mechanism in terms of electron-transfer kinetics. For example, faster electrocatalytic reaction kinetics lead to a smaller Tafel slope which is shown in a significant current density increment as a function of the overpotential change (Figure 6).

Koutecký and Levich analysis

The exchange current density (i kin0) describes the charge transfer under equilibrium conditions. A higher exchange current density means a higher charge transfer rate and a lower reaction barrier. As explained earlier in this article, for a better electrocatalyst, a lower Tafel slope and a higher exchange current density are expected.

When performing real experiments, mass transport is the limiting factor at higher overpotentials (Figure 5) which leads to a nonlinear slope of the Tafel plot.

To overcome the undesirable impacts of mass transport (e.g. diffusion), a Rotating Disc Electrode (RDE) (Figure 3) is used. The current signal is therefore measured at different rotation rates. From this data set, it is possible to extract the pure kinetic current (i kin0) according to Koutecký and Levich (Figure 6).

Figure 6. Tafel plot of OER for two different catalysts. The exchange current density (i kin0) is determined by extrapolation to η = 0.

You can find more information about Koutecký and Levich analysis by downloading our free Application Note:  

Impedance analysis

Another measuring technique can be used to determine the reaction kinetics of catalysts: electrochemical impedance spectroscopy (EIS). One of the most important advantages of impedance spectroscopy is that it is a non-destructive and non-invasive measuring technique. This enables consecutive measurements to be performed on the same sample, such as experiments at different temperatures or at different current densities. Also, the aging effects of catalysts can easily be determined this way.

Impedance spectroscopy is an alternating electric current (AC) technique, where an AC voltage with a very small amplitude of a few millivolts is applied to the electrode which responds with an AC current. The values of the applied voltage signal and the values of the corresponding current signal are used to calculate the AC resistance—the impedance. A broad frequency range of several decades is applied and this enables the identification of the kinetic and transport processes that take place on the electrode over different time scales.

Displaying the impedance spectra in a Nyquist plot (Figure 7) exhibits the charge transfer resistance of the reaction as a semicircle. The diameter of this semicircle corresponds to the reaction kinetics: the smaller the diameter, the faster the kinetics of the reaction.

Figure 7. Example of a Nyquist plot of two different catalysts with different activities.

Electrochemical impedance spectroscopy does not only provide kinetic information to researchers, it also gives insight into mass transport effects and conductivity of electrolytes and membranes.

To find out more about EIS, check out our selection of free Application Notes:

Stability

For industrial use, a catalyst should exhibit an extremely low degradation rate. It needs to be stable for many operating hours. At the development stage, stability is an important factor to determine whether a catalyst has the potential for use in practical applications. Stability can be characterized by the changes of the overpotential or current over time by using chronoamperometry, chronopotentiometry, and cyclic voltammetry. These are described in the following sections.
Chrono methods (chronoamperometry and chronopotentiometry)

When using a chronoamperometry method, a constant voltage is applied to the catalyst and the corresponding current signal is sampled and plotted as an i/t curve (Figure 8).

Figure 8. Chronoamperometry measurement of two different catalysts for OER.

Conversely, when using a chronopotentiometry method, a constant current is applied to the catalyst and the voltage response is measured and plotted as an E/t curve (Figure 9). For this measurement, the longer the tested current or potential remains constant, the better the stability of the catalyst.

Figure 9. Chronopotentiometry measurement of two different catalysts for OER.
Cyclic Voltammetry

Cyclic voltammetry is a technique that measures the current density by cycling the potential of the working electrode linearly versus time (Figure 10) . In contrast to linear sweep voltammetry (Figure 4), after the end potential is reached, the potential in a CV experiment is scanned in the opposite direction to return to the initial potential.

Figure 10. Example of a cyclic voltammetry (CV) diagram with one cycle shown.

To determine the degradation rate of a tested catalyst, usually more than 5000 cycles must be executed with a scan rate between 50–100 mV/s. Before and after CV cycling, linear sweep voltammetry (LSV) is used to examine the overpotential shift at a specific current density.

The smaller the change of the overpotential, the better the electrocatalyst’s stability.

Efficiency

The efficiency (η) can be determined by the faradaic efficiency (or coulombic / coulombian efficiency) in terms of experimental results compared to theoretical predictions.

To be able to calculate the theoretical hydrogen volume via Faraday’s Law, the total charge is needed. This value is measured by the potentiostat using the chronocoulometry method which records the total charge over time (Figure 11).

Figure 11. Example of a chronocoulometry plot.

Conclusion

Choosing the right technique for the analysis of activity, stability, and efficiency of catalysts depends on the specific research and development project focus. Luckily, Metrohm offers a wide range of solutions that will meet all kinds of research requirements.

Visit our website

and learn more about our wide range of solutions for electrochemical research!

Post written by Sandro Haug, Product Manager Electrochemistry at Deutsche METROHM GmbH & Co. KG, Filderstadt, Germany.

Validation of titration methods

Validation of titration methods

Manufacturing products of the highest quality is a must, especially in the pharmaceutical and food industries. This requires accurate, reproducible, and simple analysis methods that eliminate human errors as much as possible. Automated titration is one such solution that offers additional time and cost savings to laboratories.

After applying automation to a titration method, how can you ensure that the chosen method also delivers a reliable result? And how do you know that it is suitable for the analysis of your analyte(s)? This requires method validation of a titration, which includes standardization of the titrant as well as determination of accuracy and precision, linearity, and specificity.

USP General Chapter <1225> Validation of Compendial Procedures and ICH Guidance Q2(R1) Validation of Analytical Procedures: Text and Methodology define the validation elements – some of the most important ones are described in the following article.

These include (click to go to each section):

Standardization

Dilution and weighing errors as well as the constant aging of all titrants lead to changes in the concentration of the titrant. To obtain results that are as reliable as possible, the most accurate titrant concentration is a prerequisite. Standardization of the titrant is therefore an integral part of a titration method validation. The standardization procedures for various titrants are described in the Volumetric Solution section of USP – NF as well as in the Metrohm Application Bulletin AB-206 regarding the titer determination in potentiometry.

The titrant to be used in the validation must first be standardized against a primary standard or a pre-standardized titrant. It is important that the standardization step and the sample titration are carried out at the same temperature.

Primary standards are characterized by the following properties:

  • high purity and stability
  • low hygroscopicity (to minimize weight changes)
  • high molecular weight (to minimize weighing errors)

The use of a standard substance (primary standard) allows accuracy to be assessed.

For more information about titrant standardization, check out our blog posts «What to consider when standardizing titrant» (for potentiometric titration) and «Titer determination in Karl Fischer titration».

Accuracy and precision

Accuracy is defined as the proximity of the result to the true value. Therefore, it provides information about the bias of a method under validation. Accuracy should be determined over the entire concentration range.

Precision is usually expressed as the standard deviation (SD) or relative standard deviation (RSD). It expresses how well the individual results agree within an analysis of a homogeneous sample. Here, it is important that not only the analysis itself but also all sample preparation steps are performed independently for each analysis.

Precision is evaluated in three levels:

  1. Repeatability: the precision achieved by a single analyst for the same sample in a short period of time using the same equipment for all determinations.
  2. Intermediate precision: analysis of the same sample on different days, by different analysts and with different equipment, if possible, within the same laboratory.
  3. Reproducibility: precision obtained by analyzing the same sample in different laboratories.

Determination of both accuracy and precision is necessary, as only the combination of both factors ensures correct results (Figure 1).

Figure 1. Only when both precision and accuracy are high can correct results be obtained, as high precision does not necessarily mean good accuracy, and vice versa.

For titration, accuracy and repeatability are usually determined together. At least two to three determinations at three different concentration levels (in total six to nine determinations) are recommended. For assays, the recommendation is to use a concentration range of 80% to 120% of the intended sample weight.

Linearity

Linearity expresses whether a particular method gives the correct results over the concentration range of interest. Since titration is an absolute method, linearity can usually be determined directly by varying the sample size and thus the analyte concentration.

To determine the linearity of a titration method in the range of interest, titrate at least five different sample sizes and plot a linear regression of the sample volume against the titration volume consumed (Figure 2). The coefficient of determination (R2) is used to assess linearity. The recommendation is to use a concentration range of 80% to 120% of the intended sample weight.

Figure 2. Linear regression curve for the assay of potassium bicarbonate.

Specificity

Impurities, excipients, or degradation products are among the many components that may be present in a sample. Specificity is the ability to evaluate the analyte without interference from these other components. Therefore, it is necessary to demonstrate that the analytical procedure is not affected by such compounds. This is the case when either the equivalence point (EP) found is not shifted by the added impurities or excipients, or in the event it is shifted that a second EP corresponding to these added components can be observed when a potentiometric sensor is used for indication.

Specificity may be achieved by using suitable solvents (e.g., non-aqueous titration instead of aqueous titration for acid-base titration) or titration at a suitable pH value (e.g., complexometric titration of calcium at pH 12, where magnesium precipitates as magnesium hydroxide).

How can this be implemented in practice? The titrimetric determination of potassium bicarbonate with hydrochloric acid will serve as an example here.

In this case, potassium carbonate is expected as an impurity with pkb values of 8.3 and 3.89. This makes it possible to separate the two species during the acid-base titration. Figure 3 shows the comparison of a curve overlay of the titration curves of potassium bicarbonate with and without added potassium carbonate.

Figure 3. Curve overlay of the specificity test using 1 g KHCO3 with and without 0.5 g K2CO3 (green and orange = no K2CO3 added; blue and yellow = K2CO3 added). Click to enlarge.

The lower titration curve corresponds to the solution containing both potassium bicarbonate and potassium carbonate. Two EPs are found here: the first EP can be assigned to the added potassium carbonate, while the second corresponds to the sum of potassium bicarbonate and potassium carbonate. The curve at the top of the figure clearly shows only one EP for the potassium bicarbonate solution without impurities.

Find out more about the proper recognition of endpoints (EP) in our previous blog post.

Conclusion

If you follow the recommendations above, you will be ready for titration method validation – and now it`s time to get started!

Using potentiometric autotitration instead of manual titration increases the accuracy and reliability of your results. In addition, the use of an autotitrator ensures that critical regulatory compliance requirements, such as data integrity are met.

Right from the start, Metrohm products provide peace of mind and confidence in the quality of the data you produce with proper IQ/OQ.

If you would like to learn more about Metrohm Analytical Instrument Qualification, have a look at our two blog posts dedicated to this important topic.

Additional security is also provided, e.g., by Metrohm Buret Calibration which ensures that the accuracy and precision of your dosing device are within the required tolerances. Traceable monitoring of the performance and function of the instrument through regular re-qualifications and tests is therefore a given.

Watch our free webinar

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How to convert from manual to automated titration procedures

Post written by Doris Hoffmann, Product Manager Titration at Metrohm International Headquarters, Herisau, Switzerland.

The importance of titrations in pharmaceutical analysis

The importance of titrations in pharmaceutical analysis

If you are in the pharmaceutical industry and wonder if a conversion from a manual titration to an automated titration is suitable for your work, this blog post should give you all the answers you need.

I will cover the following topics in this article (click to go directly to the topic):

Applicability of modern titration methods in pharmaceutical analysis

Perhaps you have already heard or read about automated titration and its benefits in comparison to manual titration, but are now wondering whether those guidelines are also applicable to pharmaceutical analysis.

Getting straight to the point: Yes, it is true that many USP monographs as well as USP General Chapter <541> Titrimetry still refer to the manual visual endpoint titration. But there’s good news! USP-NF General Notices and Requirements Section 6.30 states:

As long as the alternative method is fully validated and you can prove that both methods are equivalent, you are allowed to use alternative methods.

Since titration still plays an important role in pharmaceutical analytical procedures and processes, Metrohm offers a variety of applications for innumerous API monographs of the United States Pharmacopeia as well as pharmacopeia-compliant analytical instruments.

Automated titration procedure

Have you wondered about how to perform the procedure of an automated titration—how does it differ from a manual titration? Working with a pharmacopeia compliant analytical instrument from Metrohm is not so different:

 

  1. Titrant is added with an automated piston buret that safely controls the delivery of titrant to a precise level.
  2. The sample is homogenized with a stirrer.
  3. The electrode detects the titration endpoint, removing subjectivity of color changes.
  4. Results are automatically calculated and displayed allowing no room for human error.
Figure 1. Anatomy of an automatic titrator.

As shown in Figure 1, an automated titration procedure mainly consists of four steps. These steps are repeated until the end of the titration (Figure 2).

In addition, all Metrohm devices that run with proprietary tiamo® or OMNIS® software are 21 CFR Part 11 compliant meeting all ALCOA+ requirements. Thanks to improvements in productivity, accuracy, and precision, the human influence on analysis is reduced to a minimum.

Figure 2. The titration cycle illustrating the different steps in an automated titration procedure.

If you are wondering how to transfer a manual titration to automated titration, then check out our earlier blog posts on this topic. Also, download our free white paper comparing manual and automated titration.

Choice of electrodes for pharmaceutical titrations

For autotitration, either an electrode or a photometric sensor is used to detect the point of a sample analyte neutralization. Metrohm offers a wide range of different electrodes for titrations that are extremely suitable for various pharmaceutical applications. The electrode choice depends on the type of reaction, the sample, and the titrant used.

Download our free brochure to learn more.

If you want to know more about how endpoints are recognized using electrodes or photometric sensors, read our previous blog post to find out how the endpoint is determined during an autotitration.

Maybe you are not quite sure which is the best electrode for your application. Therefore, Table 1 shows an interactive electrode guide for different pharmaceutical titrations.

Table 1. Electrode guide for pharmaceutical titrations.
Type of titration Electrode Close-up view Pharma Application / API

Aqueous acid/base titrations

e.g. titrant is NaOH or HCl

phenolphthalein indicator

Combined pH electrode with reference electrolyte c(KCl) = 3 mol/L

e.g. Ecotrode Plus, Unitrode

Water-soluble acidic and basic active pharmaceutical ingredients (API) and excipients

API: Benzbromaron, Potassium carbonate, Potassium bicarbonate

Non-aqueous acid/base titrations

e.g. solvent is organic or glacial acetic acid

crystal violet indicator

Combined pH electrode with alcoholic reference electrolyte LiCl in EtOH

e.g. Solvotrode easyClean

Water-insoluble weak acids and bases

Assay of API

Acid value (free fatty acids)

API: Caffeine, Ketoconazole

Redox titrations

e.g. titrant is sodium thiosulfate

starch indicator

Pt metal electrode

e.g. combined Pt ring electrode, Pt Titrode

 

Antibiotic assays

Peroxide value in fats and oils

API: Captropril, Paracetamol, Sulfonamide

Precipitation titrations

e.g. titrant is silver nitrate

ferric ammonium sulfate indicator

Ag metal electrode

e.g. combined Ag ring electrode, Ag Titrode

Chloride content in pharmaceutical products

Iodide in oral solutions

API: Dimenhydrinate

Complexometric titrations

e.g. titrant is EDTA

hydroxy naphthol blue indicator

Ion-selective electrode

e.g. combined calcium-selective electrode with polymer membrane

Calcium content in pharmaceutical products

API: Calcium succinate

Photometric titration

e.g. titrant is EDTA

Eriochrome black T indicator

Photometric sensor

e.g. Optrode

Assay of various metal salts in APIs

API: Chondroitin sulfate, Bismuth nitrate, Zinc sulfate

To help you select the best electrode for your titrations, we have prepared a poster for you to easily find the perfect electrode for USP monographs. Additionally, you will find information about proper sensor maintenance and storage.

If you prefer, the Metrohm Electrode Finder is even easier to use. Select the reaction type and application area of your titration and we will present you with the best solution.

As documentation and traceability are critical for the pharmaceutical industry, Metrohm has developed fully digital electrodes, called «dTrodes». These dTrodes automatically store important sensor data, such as article number and serial number, calibration data and history, working life, and the calibration validity period on an integrated memory chip.

Conclusion

Metrohm is your qualified partner for all chemical and pharmaceutical analysis concerns and for analytical method validation.

In addition to full compliance with official directives, Metrohm instruments and applications comply with many of the quality control and product approval test methods cited in pharmacopoeias. Discover the solutions Metrohm offers the pharmaceutical industry (and you in particular!) for ensuring the quality and safety of your products.

Learn even more about the practical aspects of modern titration in our monograph and visit our Webinar Center for informative videos.

Need a reason to switch

from manual to automated titration?

How about FIVE?

Post written by Doris Hoffmann, Product Manager Titration at Metrohm International Headquarters, Herisau, Switzerland.