Select Page
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

available on demand!

How to convert from manual to automated titration procedures

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

How much do pipes rust in a year?

How much do pipes rust in a year?

Why is corrosion important?

According to the Association of Materials Protection and Performance (AMPP) the total estimated annual cost of corrosion is as high as 3.5% of a country’s GDP [1]. An AMPP international study [2] found that in the United States alone, the corrosion related cost can be as high as $1.4 billion USD annually in the oil and gas exploration and production sector. This figure climbs even higher, up to $40 billion USD for gas and drinking water distribution plus sewer systems. This is an unavoidable problem with a high cost to bear.

Even though the corrosion itself isn’t unavoidable, it can be controlled by using the right material in the right place. Using a reliable test method that evaluates the material’s resistance against corrosion and predicts its potential failure is of the utmost importance. This test method should also be cost-effective and practicable.

What is corrosion?

Corrosion refers to a naturally occurring process that involves the deterioration or degradation of metals and alloys through a chemical reaction. The corrosion rate is highly dependent on the type of material, ambient temperature, contaminants/impurities, and other environmental factors. Most corrosion phenomena are electrochemical in nature and consist of at least two reactions on the surface of the metals or alloys.

For example:

These electrochemical process require three main elements:

  • Anode: where the metal corrosion occurs.
  • Cathode: the electrical conductor, which is not consumed during the corrosion process in the real-life electrochemical cell configuration.
  • Electrolyte: the corrosive medium that enables the transfer of electrons between the anode and the cathode.

Depending on the materials and environment, corrosion can occur in different ways, such as uniform corrosion, pitting corrosion, crevice corrosion, galvanic corrosion, or microbiologically induced corrosion to name just a few. Learn more about the different types of corrosion in our free white paper.

This white paper also includes details about relevant electrochemical techniques including Linear Sweep Voltammetry (LSV), Electrochemical Impedance Spectroscopy (EIS), and Electrochemical Noise (ECN or ZRA). These techniques allow for the exploration of corrosion mechanisms, the behavior of different materials, the rate at which corrosion occurs, and also to determine the suitability of the corrosion protection solutions such as protective coatings and inhibitors, among others.

Find out more about these subjects individually with our selection of free Application Notes (AN).
Calculation of corrosion parameters with NOVA – Tafel plot corresponding to corrosion behavior of iron in seawater. (Click to enlarge)

Creating pipe-flow conditions in your corrosion laboratory

Internal corrosion is the most problematic cause of pipeline failure. To understand the fundamentals about corrosion failure and its root causes within pipelines, a similar environment should be created in the lab.

The Rotating Cylinder Electrode (RCE) is an integral part of creating hydrodynamic electrochemical experiments in the lab that create turbulent flow conditions which realistically simulate the situation for liquids flowing through pipes. The RCE can be used with most electrochemical techniques such as chronoamperometry, chronopotentiometry, and potential sweep.

Study of the corrosion rate as a function of rotation speed (convective flux) is one of the most common applications for the RCE. Corrosion studies can be performed using linear or cyclic polarization measurements (LP, DPD, CP), electrochemical impedance spectroscopy (EIS), and electrochemical noise (ECN) with respect to the rotation speed.

Results obtained by electrochemical methods are more accurate and are obtained much faster than conventional corrosion investigation methods (e.g. salt spray), providing more efficiency and productivity to any corrosion measurement laboratory. Learn about the RCE and how to simulate realistic pipe-flow conditions in the lab combined with electrochemical corrosion techniques in our free white paper.

One typical method in electrochemical corrosion studies is linear polarization (LP). With this method, it is possible to evaluate the corrosion behavior of a sample under pipe-flow (i.e. turbulent flow) conditions and learn about the corrosion rate of the sample at a specific flow rate.

Metrohm offers two Application Notes that use this technique specifically:

The Tafel plot obtained from LP measurement gives an indication of the corrosion potential. Using dedicated analysis tools in the NOVA software from Metrohm Autolab, the corrosion rate analysis can be performed and corrosion rate can be calculated, giving an indication of how much the pipe will rust in a year (in mm/year) under given conditions. Once this information is available for a certain material, a more corrosion resistive environment can be developed by applying a certain coating or a corrosion inhibitor.

Tafel plot created by Metrohm Autolab’s NOVA software. Blue line is measured without corrosion inhibitor and red line is measured with corrosion inhibitor.
Tafel plot created by Metrohm Autolab’s NOVA software corresponding to the measurements done in quiescent electrolyte (blue) and under 500 RPM rotation rate (red). All other experimental parameters were kept the same.

A second evaluation can be performed to learn how much the pipe will rust in a year, under these resistive conditions. In the example below, under standard conditions, the corrosion rate of carbon steel is measured at 0.25 mm/yr. However, when a specific corrosion inhibitor is used (tryptamine in this case), the performance is significantly improved and the corrosion rate drops to 0.065 mm/yr. These results can be achieved in a matter of minutes by using electrochemical methods, whereas by conventional methods (e.g., salt spray chamber combined with weight loss analysis), it takes up to a few months to conclude the results. That is a huge difference in efficiency!

Corrosion Parameter No Inhibitor With Inhibitor
Ecorr (V) from linear regression -0.479 -0.392
Ecorr (V) from Tafel analysis -0.482 -0.396
Rp (Ω) from linear regression 42.62 135.96
Rp (Ω) from Tafel analysis 43.32 136.39
Corrosion rate (mm/year) from Tafel analysis 0.25 0.065
Linear regression and Tafel analysis data resulting from experiments with and without corrosion inhibitor.

Summary

Understanding the corrosion behavior of a material under real-life conditions helps manufacturers to more quickly optimize the material design in terms of corrosion resistance, either by using a more suitable material for the pipes or by using adequate corrosion protection methods (i.e., coatings or corrosion inhibitors), which results in significant cost savings and safer operation.

Post written by Dr. Reza Fathi, Product Specialist at Metrohm Autolab, Utrecht, The Netherlands.

Recognition of endpoints (EP)

Recognition of endpoints (EP)

Like many of you, I gained my first practical titration experience during my chemistry studies in school. At this time, I learned how to perform a manual visual endpoint titration – and I can still remember exactly how I felt about it.

Using a manual buret filled with titrant, I added each drop individually to an Erlenmeyer flask that contained the sample solution (including the analyte to be measured) and the indicator which was added prior to the titration. With each drop and even slight color change of my sample solution, minutes passed with increasing uncertainty. I asked myself, «Have I already reached the true endpoint, should I add another drop, or have I even over-titrated?» You have probably been in the same situation yourself!

Sound familiar to you? Don’t forget to check out our other blog post about the main error sources in manual titration!

Several years have passed since then, and I am glad that I no longer have to face the challenges of performing a manual titration because Metrohm offers the possibility of automated titrations.

If you want to know how to determine the endpoint in an automated titration, I will give you all the answers you need. In the following article I will cover these topics (click to go directly to each):

    Different detection principles – an overview

    At this point you may ask yourself—if not visually, how the endpoint (EP) can be detected in an automated titration? Well, aside from the visual endpoint recognition (e.g., by a color change, the appearance of turbidity, or appearance of a precipitate), a titration EP can also be detected by the automated monitoring of a change in a chemical or physical property which occurs when the reaction is complete.

    As shown in the table below, there are many different detection principles:

    Now, let’s discuss the potentiometric and photometric EP determination in comparison to a visually recognized EP detection as they are the most commonly used determination principles for automated titrations. If you’d like to learn more about the principles of thermometric titration, read our blog post about the basics!

    Potentiometric principle

    As shown in the table above, in the potentiometric principle the concentration dependent potential (mV) of a solution is measured against a reference potential. Therefore, a silver-silver chloride (Ag/AgCl) reference electrode is used in combination with a measuring electrode (pH sensitive glass membrane or metal ring). In general, a combined sensor (electrode) including both measuring and reference electrode is used.

    Figure 1 illustrates with a simple example how a manual titration with a color change looks when being converted to an automatic system.

    Figure 1. Illustration of the same titration performed manually (left) and automatically (right).

    Step 1: Beginning of the titration before titrant is added.

    Step 2: Addition of titrant – as the titration approaches the endpoint you begin to see signs of the color change. At this point in an automatic titration the sensor will detect a change in mV signal and the titrator begins dosing the titrant in smaller volumes and at a slower rate.

    Step 3: Finally, the EP is reached with a faint pink color which corresponds with the inflection point in the titration curve.

    Step 4: Titrating beyond the endpoint leads to over titration, and here the mV signal is fairly constant.

    This is how you achieve the characteristic S-shaped titration curve you see when performing an automated titration.

    Not only acid-base titrations can be converted. Figure 2 shows how a simple chloride titration can be converted. The titrant, titrant concentration, sample size, and sample preparation remain the same.

    Figure 2. Illustration of a chloride titration – conversion from manual to automatic analysis.

    Only the indicator is replaced by the Ag Titrode, a silver ring electrode, and we get a titration curve (Figure 2, right side) with a clearly defined endpoint.

    For more examples of possible potentiometric titrations, download our free monograph «Practical Titration» or check out our Application Finder where you can find several examples for all endpoint recognition principles.

    Photometric Principle

    Titrations using color indicators are still widely used e.g. in pharmacopeias. When performed manually, the results depend, quite literally, on the eye of the beholder. Photometric titration using the Optrode makes it possible to replace this subjective determination of the equivalence point with an objective process that is completely independent of the human eye.

    The advantage here is that the chemistry does not change – that is, the standard operating procedure (SOP) generally does not have to be adapted. 

    The basis of photometric indication is the change in intensity at a particular wavelength of a light beam passing through a solution. The transmission is the primary measured variable in photometry, and is given by the light transmission (mV or % transmission) of a colored or turbid solution that is measured with a photometric sensor such as the Optrode from Metrohm.

    There are eight possible wavelengths to choose from that span nearly all color indicators used for titrations (see table below). The shaft is solvent resistant and there is no maintenance required. It connects directly to the titrator and improves accuracy and repeatability of color indicated titrations.

    I’ve also picked an example to show you how to convert an EDTA titration of manganese sulfate from manual titration to automated titration. Like in the example above, the procedure remains the same.

    Are you ready to take the leap and switch to using an automated titration system? Read our other blog post to learn more about how to transfer manual titration to autotitration.

    One advantage of automated titration is that a lower volume of chemicals is needed, resulting in less waste. With the same indicator Eriochrome Black TS, the Optrode is used at a wavelength of 610 nm. The titration curve (Figure 3, right side) shows a large potential change of the mV signal indicating a clearly defined titration endpoint.

    Figure 3. Illustration of the photometric EDTA titration of manganese sulfate according to USP.

    If you are not sure what the optimal wavelength for your titration is, then have a look at our blog post about photometric complexometric titration to learn more!

    Comparison: Optrode vs. potentiometric electrodes

    When you decide to make the switch to automated titration, there are some points to consider when comparing the Optrode with other Metrohm potentiometric electrodes. The following table lists the main criteria.

    1Optrode has a working life of tens of thousands of hours.

    You see, an autotitration is quite simple to perform and has the great advantage that a clearly defined endpoint is given.

    Believe me, whenever I`m working with such a device including a suitable electrode for an automatic titration, I have a big smile on my face thinking back to my university days: Bye bye subjectivity, time-consuming procedure, economic inefficiency and non-traceability!

    Maybe you are now also convinced to make the change in your laboratory.

    Save more money

    with automated titration

    Read our blog post to find out more.

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

    Introduction to Analytical Instrument Qualification – Part 2

    Introduction to Analytical Instrument Qualification – Part 2

    Welcome back to our blog, and happy 2021! We hope that you and your families had a safe and restful holiday season. To start the year, we will conclude our introduction to Analytical Instrument Qualification. 

    Metrohm’s approach to Analytical Instrument Qualification (AIQ)

    Metrohm’s answer to Analytical Instrument Qualification is bundled in our Metrohm Compliance Services. The most thorough level of documentation offered for AIQ is the IQ/OQ.

    Metrohm IQ/OQ documentation provides you with the required documentation in strict accordance to the major regulations from the USP, FDA, GAMP, and PIC/S, allowing you to document the suitability of your Metrohm instruments for your lab’s specific intended use.

    With our test procedures (described later in more detail), we can prove that the hardware and software components function correctly, both individually and as part of the system as a whole. With Metrohm’s IQ/OQ, you are supported in the best possible way to integrate our systems into your current processes.

    Our high quality documentation will have you «audit ready» all the time.

    The flexibility of a modular document structure

    Depending on the environment you work in and your specific demands, Metrohm can offer a tailored qualification approach thanks to documentation modularity. If you need a lower level of qualification, only the required modules can be executed. Our documentation consists of different modules, each of which documents the identity of the Metrohm representative along with the qualification reviewer, combined with the details of each instrument, software, and document involved in the qualification.  Thanks to this, each module is independent, which guarantees both full traceability and reliability for your system setup.

    Cost-effective qualification from Metrohm

    Metrohm supports you by implementing a cost-effective qualification process, depending upon your requirements and the modules needed. This means that a qualification is not about performing unnecessary actions, qualification is about completing the required work.

    The risk assessment analysis defines the level of qualification needed and based on it, we focus on testing only what needs to be tested. In case you relocate your device to another lab, which qualification steps (DQ, IQ, OQ, PQ) are really needed in order to fulfill your requirements? Contact your local Metrohm expert for advice on this matter.

    A complete Metrohm IQ/OQ qualification includes…

    Metrohm IQ/OQ documentation is based on the following documentation tree, beginning with the first module, the Master Document (MD), followed by the Installation Qualification (IQ) and eventually the Operational Qualification (OQ). The OQ is then divided again into individual component tests (Hardware and Software) and a holistic test to validate your complete system.

    Master Document (MD)

    Each qualification starts with the Master Document (MD) – the central organizing document for the AIQ procedures. It not only describes the process of installing and qualifying the instruments, but also the competence and education level of the qualifying engineer. The MD identifies all other components to be added to the qualification, resulting in a flexible framework on which to build up a set of documentation.

    Installation Qualification (IQ)

    Once the content of the documentation is defined in the MD, the Installation Qualification (IQ) follows. This set of documentation is designed to ensure that the instrument, software, and any accessories have been all delivered and installed correctly. The IQ protocol additionally specifies that the workplace is suitable for the analytical system as stipulated by Metrohm.

    Operational Qualification (OQ)

    After a correct installation comes the main part of the qualification: the Operational Qualification (OQ). In the first part of the OQ, the functionality of the single hardware components is tested and evaluated according to a set of procedures. This is to ensure that the instrument is working perfectly as designed, and is safe to use. Rest assured that you can rely on the expertise of our Metrohm certified engineers to conduct these comprehensive tests on your instruments using the necessary calibrated and certified tools.

    The second part of the OQ consists of a set of Software Tests to prove that the installed Metrohm software functions correctly and reliably on the computer it was installed on. The importance of maintaining software in a validated state is also related to the data integrity of your laboratory. Therefore these software tests can be repeated periodically or after major changes. In particular, these functionality tests cover verifications on user management, database functionalities, backups, audit trail review, security policy, electronic signatures, and so on.

    At Metrohm, we constantly work to improve our procedures and use state of the art tools and technologies.  For this reason, we have implemented a completely automated test procedure for validating the software of our new OMNIS platform. This ensures full integrity in the execution and delivers consistent results with a faster and completely error-free test execution. This innovative and automated software validation eliminates manual activities that are labor intensive and time consuming. This therefore expedites testing and removes the inefficiencies that plague the paper-based software validation.

    Your benefit is clear: save valuable time and reduce unnecessary laboratory start-up activities during qualification. That’s time you can spend on other work in your lab!

    Holistic Test (Performance Verification, PV)

    Once each individual component has been separately tested, the performance of the system as a whole is proven by means of a holistic test (OQ-PV).

    This includes a series of «wet-chemical» tests, performed using certified reference materials, to prove the system is capable of generating quality data, i.e. results that are accurate, precise, and above all fit for purpose. Based on detailed, predefined instructions (SOPs), a series of standard measurements are performed, statistically evaluated, and compared to the manufacturer’s specifications.

    Differences between Performance Verification (PV) and Performance Qualification (PQ)

    The Performance Verification (PV) is a set of tests offered by Metrohm in order to verify the fitness for purpose of the instrument. As mentioned in the previous paragraph, the PV includes standardized test procedures to ensure the system operates as designed by the manufacturer in the selected environment.

    On the other hand, the Performance Qualification (PQ) is a very customer specific qualification phase (see the «4 Q’s» Qualification Phases found in Part 1). PQ verifies the fitness for purpose of the instrument under actual condition of use, proving its continued suitability. Therefore, PQ tests are defined depending on your specific analysis and acceptance criteria.

    Now my questions to you—is your analytical instrument qualified for its intended use? Is your lab in compliance with the latest regulations for equipment qualification and validation? Get expert advice directly from your local Metrohm agency and request your quote for Metrohm qualification services today!

    Check out our online material:

    Metrohm Quality Service

    Post written by Lara Casadio, Jr. Product Manager Service at Metrohm International Headquarters, Herisau, Switzerland.

    «Analyze This»: 2020 in review

    «Analyze This»: 2020 in review

    I wanted to end 2020 by thanking all of you for making «Analyze This» – the Metrohm blog for chemists such a success! For our 60th blog post, I’d like to look back and focus on the wealth of interesting topics we have published this year. There is truly something for everyone: it doesn’t matter whether your lab focuses on titration or spectroscopic techniques, or analyzes water samples or illicit substances – we’ve got you covered! If you’re looking to answer your most burning chemical analysis questions, we have FAQs and other series full of advice from the experts. Or if you’re just in the mood to learn something new in a few minutes, there are several posts about the chemical world to discover.

    We love to hear back from you as well. Leaving comments on your favorite blog posts or contacting us through social media are great ways to voice your opinion—we at Metrohm are here for you!

    Finally, I wish you and your families a safe, restful holiday season. «Analyze This» will return on January 11, 2021, so subscribe if you haven’t already done so, and bookmark this page for an overview of all of our articles grouped by topic!

    Stay healthy, and stay curious.

    Best wishes,

    Dr. Alyson Lanciki, Scientific Editor, Metrohm AG

    Quickly jump directly to any section by clicking a topic:

    Customer Stories

    We are curious by nature, and enjoy hearing about the variety of projects where our products are being used! For some examples of interesting situations where Metrohm analytical equipment is utilized, read on.

    From underwater archaeological research to orbiting Earth on the International Space Station, Metrohm is there! We assist on all types of projects, like brewing top quality beers and even growing antibiotic-free shrimp – right here in Switzerland.

    Interested in being featured? Contact your local Metrohm dealer for details!

    Titration

    Metrohm is the global market leader in analytical instruments for titration. Who else is better then to advise you in this area? Our experts are eager to share their knowledge with you, and show this with the abundance of topics they have contributed this year to our blog.

    For more in-depth information about obtaining the most accurate pH measurements, take a look at our FAQ about pH calibration or read about avoiding the most common mistakes in pH measurement. You may pick up a few tips!

    Choose the best electrode for your needs and keep it in top condition with our best practices, and then learn how to standardize titrant properly. Better understand what to consider during back-titration, check out thermometric titration and its advantages and applications, or read about the most common challenges and how to overcome them when carrying out complexometric titrations

    If you are interested in improving your conductivity measurements, measuring dissolved oxygen, or the determination of oxidation in edible fats and oils, check out these blog posts and download our free Application Notes and White Papers!

    Finally, this article about comprehensive water analysis with a combination of titration and ion chromatography explains the many benefits for laboratories with large sample loads. The history behind the TitrIC analysis system used for these studies can be found in a separate blog post.

    Karl Fischer Titration

    Metrohm and Karl Fischer titration: a long history of success. Looking back on more than half a century of experience in KFT, Metrohm has shaped what coulometric and volumetric water analysis are today.

    Aside from the other titration blog posts, our experts have also written a 2-part series including 20 of the most frequently asked questions for KFT arranged into three categories: instrument preparation and handling, titration troubleshooting, and the oven technique. Our article about how to properly standardize Karl Fischer titrant will take you step by step through the process to obtain correct results.

    For more specific questions, read about the oven method for sample preparation, or which is the best technique to choose when measuring moisture in certain situations: Karl Fischer titration, near-infrared spectroscopy, or both?

    Ion Chromatography (IC)

    Ion chromatography has been a part of the Metrohm portfolio since the late 1980s. From routine IC analysis to research and development, and from stand-alone analyzers to fully automated systems, Metrohm has provided IC solutions for all situations. If you’re curious about the backstory of R&D, check out the ongoing series about the history of IC at Metrohm.

    Metrohm IC user sitting at a laboratory bench.

    Common questions for users are answered in blog posts about IC column tips and tricks and Metrohm inline ultrafiltration. Clear calculations showing how to increase productivity and profitability in environmental analysis with IC perfectly complement our article about comprehensive water analysis using IC and titration together for faster sample throughput.

    On the topic of foods and beverages, you can find out how to determine total sulfite faster and easier than ever, measure herbicides in drinking water, or even learn how Metrohm IC is used in Switzerland to grow shrimp!

    Near-Infrared Spectroscopy (NIRS)

    Metrohm NIRS analyzers for the lab and for process analysis enable you to perform routine analysis quickly and with confidence – without requiring sample preparation or additional reagents and yielding results in less than a minute. Combining visible (Vis) and near-infrared (NIR) spectroscopy, these analyzers are capable of performing qualitative analysis of various materials and quantitative analysis of a number of physical and chemical parameters in one run.

    Our experts have written all about the benefits of NIR spectroscopy in a 4-part series, which includes an explanation of the advantages of NIRS over conventional wet chemical analysis methods, differences between NIR and IR spectroscopy, how to implement NIRS in your laboratory workflow, and examples of how pre-calibrations make implementation even quicker.

    A comparison between NIRS and the Karl Fischer titration method for moisture analysis is made in a dedicated article.

    A 2-part FAQ about NIRS has also been written in a collaboration between our laboratory and process analysis colleagues, covering all kinds of questions related to both worlds.

    Raman Spectroscopy

    This latest addition to the Metrohm family expands the Metrohm portfolio to include novel, portable instruments for materials identification and verification. We offer both Metrohm Raman as well as B&W Tek products to cover a variety of needs and requirements.

    Here you can find out some of the history of Raman spectroscopy including the origin story behind Mira, the handheld Raman instrument from Metrohm Raman. For a real-world situation involving methamphetamine identification by law enforcement and first responders, read about Mira DS in action – detecting drugs safely in the field.

    Mira - handheld Raman keeping you safe in hazardous situations.

    Are you looking for an easier way to detect food fraud? Our article about Misa describes its detection capabilities and provides several free Application Notes for download.

    Process Analytics

    We cater to both: the laboratory and the production floor. The techniques and methods for laboratory analysis are also available for automated in-process analysis with the Metrohm Process Analytics brand of industrial process analyzers.

    Learn about how Metrohm became pioneers in the process world—developing the world’s first online wet chemistry process analyzer, and find out how Metrohm’s modular IC expertise has been used to push the limits in the industrial process optimization.

    Additionally, a 2-part FAQ has been written about near-infrared spectroscopy by both laboratory and process analysis experts, which is helpful when starting out or even if you’re an advanced user.

    Finally, we offer a 3-part series about the advantages of process analytical technology (PAT) covering the topics of process automation advantages, digital networking of production plants, and error and risk minimization in process analysis.

    Voltammetry (VA)

    Voltammetry is an electrochemical method for the determination of trace and ultratrace concentrations of heavy metals and other electrochemically active substances. Both benchtop and portable options are available with a variety of electrodes to choose from, allowing analysis in any situation.

    A 5-part series about solid-state electrodes covers a range of new sensors suitable for the determination of «heavy metals» using voltammetric methods. This series offers information and example applications for the Bi drop electrode, scTrace Gold electrode (as well as a modified version), screen-printed electrodes, and the glassy carbon rotating disc electrode.

    Come underwater with Metrohm and Hublot in our blog post as they try to find the missing pieces of the ancient Antikythera Mechanism in Greece with voltammetry.

    If you’d like to learn about the combination of voltammetry with ion chromatography and the expanded application capabilities, take a look at our article about combined analysis techniques.

    Electrochemistry (EC)

    Electrochemistry plays an important role in groundbreaking technologies such as battery research, fuel cells, and photovoltaics. Metrohm’s electrochemistry portfolio covers everything from potentiostats/galvanostats to accessories and software.

    Our two subsidiaries specializing in electrochemistry, Metrohm Autolab (Utrecht, Netherlands) and Metrohm DropSens (Asturias, Spain) develop and produce a comprehensive portfolio of electrochemistry equipment.

    This year, the COVID-19 pandemic has been at the top of the news, and with it came the discussion of testing – how reliable or accurate was the data? In our blog post about virus detection with screen-printed electrodes, we explain the differences between different testing methods and their drawbacks, the many benefits of electrochemical testing methods, and provide a free informative White Paper for interested laboratories involved in this research.

    Our electrochemistry instruments have also gone to the International Space Station as part of a research project to more efficiently recycle water on board spacecraft for long-term missions.

    The History of…

    Stories inspire people, illuminating the origins of theories, concepts, and technologies that we may have become to take for granted. Metrohm aims to inspire chemists—young and old—to be the best and never stop learning. Here, you can find our blog posts that tell the stories behind the scenes, including the Metrohm founder Bertold Suhner.

    Bertold Suhner, founder of Metrohm.

    For more history behind the research and development behind Metrohm products, take a look at our series about the history of IC at Metrohm, or read about how Mira became mobile. If you are more interested in process analysis, then check out the story about the world’s first process analyzer, built by Metrohm Process Analytics.

    Need something lighter? Then the 4-part history of chemistry series may be just what you’re looking for.

    Specialty Topics

    Some articles do not fit neatly into the same groups as the rest, but are nonetheless filled with informative content! Here you can find an overview of Metrohm’s free webinars, grouped by measurement technique.

    If you work in a regulated industry such as pharmaceutical manufacturing or food and beverage production, don’t miss our introduction to Analytical Instrument Qualification and what it can mean for consumer safety!

    Industry-focused

    Finally, if you are more interested in reading articles related to the industry you work in, here are some compilations of our blog posts in various areas including pharmaceutical, illicit substances, food and beverages, and of course water analysis. More applications and information can be found on our website.

    Food and beverages
    All of these products can be measured for total sulfite content.

    Oxidation stability is an estimate of how quickly a fat or oil will become rancid. It is a standard parameter of quality control in the production of oils and fats in the food industry or for the incoming goods inspection in processing facilities. To learn more about how to determine if your edible oils are rancid, read our blog post.

    Determining total sulfite in foods and beverages has never been faster or easier than with our IC method. Read on about how to perform this notoriously frustrating analysis and get more details in our free LC/GC The Column article available for download within.

    Measuring the true sodium content in foodstuff directly and inexpensively is possible using thermometric titration, which is discussed in more detail here. To find out the best way to determine moisture content in foods, our experts have written a blog post about the differences between Karl Fischer titration and near-infrared spectroscopy methods.

    To determine if foods, beverages, spices, and more are adulterated, you no longer have to wait for the lab. With Misa, it is possible to measure a variety of illicit substances in complex matrices within minutes, even on the go.

    All of these products can be measured for total sulfite content.

    Making high quality products is a subject we are passionate about. This article discusses improving beer brewing practices and focuses on the tailor-made system built for Feldschlösschen, Switzerland’s largest brewer.

    Pharmaceutical / healthcare

    Like the food sector, pharmaceutical manufacturing is a very tightly regulated industry. Consumer health is on the line if quality drops.

    Ensuring that the analytical instruments used in the production processes are professionally qualified is a must, especially when auditors come knocking. Find out more about this step in our blog post about Analytical Instrument Qualification (AIQ).

    Moisture content in the excipients, active ingredients, and in the final product is imperative to measure. This can be accomplished with different analytical methods, which we compare and contrast for you here.

    The topic of virus detection has been on the minds of everyone this year. In this blog post, we discuss virus detection based on screen-printed electrodes, which are a more cost-effective and customizable option compared to other conventional techniques.

    Water analysis

    Water is our business. From trace analysis up to high concentration determinations, Metrohm has you covered with a variety of analytical measurement techniques and methods developed by the experts.

    Learn how to increase productivity and profitability in environmental analysis laboratories with IC with a real life example and cost calculations, or read about how one of our customers in Switzerland uses automated Metrohm IC to monitor the water quality in shrimp breeding pools.

    If heavy metal analysis is what you are interested in, then you may find our 5-part series about trace analysis with solid-state electrodes very handy.

    Unwanted substances may find their way into our water supply through agricultural practices. Find out an easier way to determine herbicides in drinking water here!

    Water is arguably one of the most important ingredients in the brewing process. Determination of major anions and cations along with other parameters such as alkalinity are described in our blog post celebrating International Beer Day.

    All of these products can be measured for total sulfite content.
    Illicit / harmful substances

    When you are unsure if your expensive spices are real or just a colored powder, if your dairy products have been adulterated with melamine, or fruits and vegetables were sprayed with illegal pesticides, it’s time to test for food fraud. Read our blog post about simple, fast determination of illicit substances in foods and beverages for more information.

    Detection of drugs, explosives, and other illegal substances can be performed safely by law enforcement officers and first responders without the need for a lab or chemicals with Mira DS. Here you can read about a real life training to identify a methamphetamine laboratory.

    Drinking water regulations are put in place by authorities out of concern for our health. Herbicides are important to measure in our drinking water as they have been found to be carcinogenic in many instances.

    Post written by Dr. Alyson Lanciki, Scientific Editor at Metrohm International Headquarters, Herisau, Switzerland.

    Introduction to Analytical Instrument Qualification – Part 2

    Introduction to Analytical Instrument Qualification – Part 1

    When talking about the subject of Analytical Instrument Qualification (AIQ), my first thought is of regulated industries, like pharmaceuticals and food. 

    You may be wondering—Why do we need to qualify analytical instruments in this environment? Why does my titrando or my OMNIS system need such a service?

    Consumer safety here is of paramount importance. Medicines that may represent a health hazard for patients or do not provide the intended therapeutic effect are undesirable and costly, therefore steps must be taken to safeguard the manufacturing process and prevent fatal implications. By qualifying the used analytical instruments, we can ensure that active ingredients and finished pharmaceutical products are manufactured in a safe environment.

    In addition, procedures that prove instrument accuracy and repeatability are a must. Metrohm qualification procedures provide this documentation, fully traceable evidence which is also required for inspections and audits by regulatory authorities.

    When auditors come knocking

    In case an auditor observes any violations of the United States Food and Drug Administration (FDA) guidelines for example, this will be communicated in an inspectoral observation or a Warning Letter. If we look to pharmaceutical Warning Letters in the past, we can see that the FDA is mainly concerned with issues related to qualification and data integrity.

    Some typical findings are e.g. the usage of an unqualified system, or the use of an instrument outside of the calibration range for which it was initially qualified. This proves the point that qualification of analytical instruments in regulated environments cannot be ignored.

    Metrohm Compliance Services can help to prove the full data traceability of your qualification activities, simplifying your audit preparation and at the same time maintaining a constant state of inspection readiness for your laboratory.

    Instruments in regulated environments need to be qualified periodically according to the main regulatory bodies. The United States Pharmacopeia (USP) is the leading pharmacopeia that has a general chapter dedicated to Analytical Instrument Qualification (AIQ), USP <1058>. Therefore, it has global significance, making laboratories subject to regulatory requirements either directly or indirectly. This is why Metrohm Compliance Services are based on this important chapter.

    What is Analytical Instrument Qualification (AIQ) exactly?

    As per USP <1058>, it is «the collection of documented evidence that an instrument performs suitably for its intended purpose.» This indicates that AIQ is the foundation for generating quality data with the needed data integrity. By using qualified instruments, you gain confidence in the validity of generated data and that your instrument meets specifications of regulatory standards.

    AIQ is not a single activity, but a continuous process over the lifetime of the instrument. AIQ already starts before the instrument purchase with the formal writing of User Requirement Specifications (URS), where the lab’s requirements for a specific instrument are documented. And yes, for e.g. a fully equipped Metrohm Dual IC system as well as for a single Metrohm pH meter, there is the same need to document the laboratory requirements and its intended use.

    After clarification of the intended use and the evaluation of the right technology, a Risk Assessment (RA) needs to be carried out to determine the required qualification strategy to prove the «fitness for purpose» of the purchased analytical instrument.

    The extent of the next qualification stages depends on the outcome of the Risk Assessment. The following activities are grouped into four phases: Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ), the so-called «4 Q’s».

    Whereas the DQ is the documented verification that the instrument specifications meet the laboratory requirements, the IQ provides the proof that the equipment has been installed properly. In the OQ phase, it’s demonstrated that the system operates correctly in the selected environment as per manufacturer specifications, while the PQ confirms that the instrument consistently performs according to your defined specifications.

    During the lifecycle of the instrument, major repairs might be needed, it might be subject to major updates / upgrades, or it might even be transferred to another lab. In all of these cases, the original URS should be reviewed again and adjusted if necessary. The URS is a living document that can and must be changed and updated when needed. Based on a risk assessment analysis, it will then be defined what the qualification steps are that should be repeated after the needed changes (IQ, OQ, PQ).

    Eventually the instrument’s life comes to an end, and we arrive at its retirement. This final step of the AIQ is often considered as the «forgotten child» of validation activities. To put this a bit more in perspective, consider when you make a new electronic purchase, such as a PC. The situation is similar to when a new analytical system is bought. It’s easier to focus on something new—concentrating on getting the training for its proper usage, and making sure it’s working correctly. We begin to ignore or forget that the old system is still there.

    Therefore, decommissioning of an instrument is a critical part of the validation process that must also be very well documented. For the old system, a final system qualification might be necessary if required. Afterwards, all data have to be removed and stored in a safe location. It is extremely important to ensure that the data can be read from this location (data migration) for a number of years, depending on your retention procedures.

    Support when and where you need it

    The fact that users have responsibilities for the instrument qualification (USP <1058>) does not mean that all qualification activities must be conducted alone!

    Metrohm supports you over the lifetime of your investment, from advising you during the purchase process to the first installation and qualification. Additionally, our IQ/OQ documentation provides you the required documentation in strict accordance with the current regulations. To ensure your Metrohm device remains in a qualified state, we offer requalification services at scheduled intervals as specified in your requirements, to guarantee the accuracy and precision of your system over its lifetime. 

    An advantage of relying on Metrohm as the manufacturer of your analytical instruments is that we have all the necessary experience for performing IQ/OQ procedures. Most importantly, our certified service engineers bring along all calibrated and certified reference instruments that are required for the qualification. To ensure the quality of Metrohm Service is maintained, our service engineers undergo compulsory re-training on a regular basis according to a globally standardized program.

    Buying Metrohm equipment is the first step to success, but maintaining it in a qualified state is the key! Just contact your local Metrohm dealer and let us handle the rest.

    For more details about which qualification phases can be fully handled by Metrohm and where we can support you, read Part 2!

    Check out our online material:

    Metrohm Quality Service

    Post written by Lara Casadio, Jr. Product Manager Service at Metrohm International Headquarters, Herisau, Switzerland.