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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.

Thermometric titration – the missing piece of the puzzle

Thermometric titration – the missing piece of the puzzle

Titration is a well-established analysis technique taught to each and every chemistry student. Titration is carried out in nearly every analytical laboratory either as manual titration, photometric titration, or potentiometric titration. In this blog entry, I would like to present an additional kind of titration you may  not have heard of before – thermometric titration – which can be considered the missing piece of the titration puzzle.

Here, I plan to cover the following topics:
  1. What is thermometric titration?
  2. Why consider thermometric titration?
  3. Practical application examples

What is thermometric titration?

At first glance, thermometric titration (TET) looks like a normal titration and you won’t see much (or any) difference from a short distance. The differences compared to potentiometric titration are in the details.

TET is based on the principle of enthalpy change (ΔH). Each chemical reaction is associated with a change in enthalpy which in turn causes a temperature change. During a titration, analyte and titrant react either exothermically (increase in temperature) or endothermically (decrease in temperature).

During a thermometric titration, the titrant is added at a constant rate and the change in temperature caused by the reaction between analyte and titrant is measured. By plotting the temperature versus the added titrant volume, the endpoint can be determined by a break within the titration curve. Figure 1 shows idealized thermometric titration curves for both exothermic and endothermic situations.

Figure 1. Illustration of exothermic and endothermic titration curves showing clear endpoints where the temperature of the solution changes abruptly.

What happens during a thermometric titration?

During an exothermic titration reaction, the temperature increases with the titrant addition as long as analyte is still present. When all analyte is consumed, the temperature decreases again as the solution equilibrates with the atmospheric temperature and/or due to the dilution of the solution with titrant (Figure 1, left graph). This temperature decrease results in an exothermic endpoint.

On the contrary, for an endothermic titration reaction, the temperature decreases with the titrant addition as long as analyte is still available. When all analyte is consumed, the temperature stabilizes or increases again as the solution equilibrates with the atmospheric temperature and/or due to the dilution of the solution with titrant (Figure 1, right graph). This temperature decrease results in an endothermic endpoint.

Knowing the absolute temperature, isolating the titration vessel, or thermostating the titration vessel is thus not required for the titration.

Figure 2. Metrohm’s maintenance-free Thermoprobe used for the reliable indication of thermometric endpoints.

In order to measure the small temperature changes during the titration, a very fast responding thermistor with a high resolution is required. These sensors are capable of measuring temperature differences of less than 0.001 °C, and allow the collection of a measuring point every 0.3 seconds (Figure 2). 

Visit the Metrohm website to learn more about the fast, sensitive Thermoprobe products available even for aggressive sample solutions.

If you would like to learn more about the theory behind TET, then download our free comprehensive monograph on thermometric titration.

Why consider thermometric titration?

Potentiometric and photometric titration are already well established as instrumental titration techniques, so why should one consider thermometric titration instead?

 

TET has the same advantages as any instrumental titration technique:
  • Inexpensive analyses: Titration instruments are inexpensive to purchase and do not have high running and maintenance costs compared to other instruments for elemental analysis (e.g., HPLC or ICP-MS).
  • Absolute method: Titration is an absolute method, meaning it is not necessary to frequently calibrate the system.
  • Versatile use: Titration is a universal method, which can be used to determine many different analytes in various industries.
  • Easy to automate: Titration can be easily automated, increasing reproducibility and efficiency in your lab.
In comparison to classical instrumental titration, thermometric titration has several additional advantages:
  • Fast titrations: Due to the constant titrant addition, thermometric titrations are very fast. Typically, a thermometric titration takes 2–3 minutes.
  • Single sensor: Regardless of the titration reaction (e.g., acid-base, redox, precipitation, …), the same sensor (Thermoprobe) can be used for all of them.
  • Maintenance-free sensor: Additionally, the Thermoprobe is maintenance free. It requires no calibration or electrolyte filling and can simply be stored dry.
  • Less solvent: Typically, thermometric titrations use 30 mL of solvent or even less. The small amount of solvent ensures that the dilution is minimized, and the enthalpy changes can be detected reliably. As a side benefit, less waste is produced.
  • Additional titrations possible: Because enthalpy change is universal for any chemical reaction, thermometric titration is not bound to finding a suitable color indicator or indication electrode. This allows the possibility of additional titrations which cannot be covered by other kinds of titration.
  • Easier sample preparation: As TET uses higher titrant concentrations it is possible to use larger sample sizes, reducing weighing and dilution errors. Tedious sample preparation steps such as filtration can be omitted as well.
Figure 3. The Metrohm 859 Titrotherm with 801 Stirrer and notebook with tiamo™ software.

Learn more about the 859 Titrotherm system for the most reliable TET determinations on the Metrohm website.

Practical application examples

In this section I would like to present you some practical examples where TET can be applied.

Acid number and base number

The acid number (AN) and base number (BN) are two key parameters in the petroleum industry. They are determined by a nonaqueous acid-base titration using KOH or HClO4, respectively, as titrant.

During such determinations, very weak acids (for AN analysis) and bases (for BN analysis) are titrated with only small enthalpy changes. Using a catalytic indicator, these weak acids and bases can also be determined by TET.

ASTM D8045 describes the analysis of the AN by thermometric titration. The benefits of carrying out this titration are:

  • Less solvent (30 mL instead of 60 or 120 mL), meaning less waste
  • Fast titration (1–3 minutes)
  • No conditioning of the sensor

If you wish to learn more about how well the results of the AN determination according to ASTM D8045 correlate with ASTM D664, download our free White Paper WP-012 as well as our brochure below.

For more detailed information about the titration itself, download the free Application Bulletin AB-427 (AN) and Application Bulletin AB-405 (BN) below.

Sodium

Using conventional titration, the salt content in foodstuff is usually determined based solely on the chloride content. However, foods usually contain additional sources of sodium, e.g. monosodium glutamate (also known as «MSG»). With TET it becomes possible to titrate the sodium directly, and thus to inexpensively determine the true sodium content in foodstuff, as stipulated in several countries.

If you wish to learn more about the sodium determination, watch our Metrohm LabCast video: «Sodium determination in food: Fast and direct thanks to thermometric titration».

Fertilizer analysis

Fertilizers consists of various nutrients, including phosphorus, nitrogen, and potassium, which are important for plant growth. TET enables the analysis of these nutrients by employing classical gravimetric reactions as the basis for the titration (e.g., precipitation of sulfate with barium). This allows for a rapid determination, without needing to wait hours for a result, as with conventional procedures based on drying and weighing the precipitate.

Nutrients which can be analyzed by TET include:
  • Phosphate
  • Potassium
  • Ammoniacal nitrogen
  • Urea nitrogen
  • Sulfate

Want to learn more about the analysis of fertilizers with thermometric titration? Download our free White Paper WP-060 on this topic. For more detailed information regarding the different fertilizer applications, check out the Metrohm Application Finder, or find a curated selection here.

Metal-organic compounds

Metal-organic compounds, such as Grignard reagents or butyl lithium compounds, are used for synthetizing active pharmaceutical ingredients (APIs) or manufacturing polymers such as polybutadiene. With TET, the analysis of these sensitive species can be performed rapidly and reliably by titrating them under inert gas with 2-butanol.

If you wish to learn more about this topic, check out our news article and download the free corresponding Application Note AN-H-142.

These were just a few examples about the possibilities of thermometric titration, to demonstrate its versatile use. For a more detailed selection, have a look at our Application Finder.

To summarize:

  • TET is an alternative titration method based on enthalpy change
  • A fast and sensitive Thermoprobe is used to determine exothermic and endothermic endpoints
  • Thermometric titration is a fast analysis technique providing results in less than 3 minutes
  • Thermometric titration can be used for various analyses, including titrations which cannot be performed otherwise (e.g., sodium determination)

I hope this overview has given you a better idea about thermometric titration – the missing piece of the titration puzzle.

For more information

Download our free Monograph:

Practical thermometric titrimetry

Post written by Lucia Meier, Technical Editor at Metrohm International Headquarters, Herisau, Switzerland.

Frequently asked questions in Karl Fischer titration – Part 2

Frequently asked questions in Karl Fischer titration – Part 2

Since I started working at Metrohm more than 15 years ago, I have received many questions about Karl Fischer titration. Some of those questions have been asked repeatedly from several people in different locations around the world. Therefore, I have chosen 20 of the most frequent questions received over the years concerning Karl Fischer equipment and arranged them into three categories: instrument preparation and handling, titration troubleshooting, and the oven technique. Part 1 covered instrument preparation and handling, and Part 2 will now focus on titration troubleshooting and the KF oven technique.

Summary of questions in the FAQ (click to go directly to each question):

Titration troubleshooting

1.  If the drift value is 0, does this mean that the titration cell is over-titrated?

A drift of zero can be a sign that the cell might be over-titrated. In combination with the mV signal (lower than end-point criteria) and the color of the working medium (darker yellow than usual), it is a clear indicator for over-titration. However, volumetric titrations sometimes exhibit a zero drift for a short time without being over-titrated. If you have a real excess of iodine in the titration cell, the result of the next determination will most likely be erroneous. Therefore, over-titration should be avoided. There are various possible reasons for over-titration, like the sample itself (e.g., oxidizing agents which generate iodine from the working medium), the electrode (coating or invisible depositions on the Pt pins/rings), the reagent, and method parameters (e.g., the titration is rate too high), to name just a few.

2.  Should I discard the Karl Fischer reagent immediately if it turns brown?

Different factors can cause over-titration, however, the reagent is not always the reason behind this issue. The indicator electrode can also be the reason for overshooting the endpoint. In this case, regular cleaning of the electrode can prevent over-titration (see also questions 7 to 9 from Part 1 in this series on cleaning).

A low stirring speed also increases the risk of over-titration, so make sure the solution is well mixed. Depending on the type of reagent, the parameters of the titration need to be adjusted. Especially if you use two-component reagents, I recommend decreasing the speed of the titrant addition to avoid over-titration. Over-titration has an influence on the result, especially if the degree of over-titration changes from one determination to the next. So over-titration should always be avoided to guarantee correct results.

3.  What is drift correction, and when should I use it?

I recommend using the drift correction in coulometric KF titration only. You can also use it in volumetric titration, but here the drift level is normally not as stable as for coulometric titrations. This can result in variations in the results. A stabilization time can reduce such an effect. However, compared to the absolute water amounts in volumetry, the influence of drift is usually negligible.

4.  My results are negative. What does a negative water content mean?

Negative values do occur if you have a high start drift and a sample with a very low water content. In this case, the value for drift correction can be higher than the absolute water content of the sample, resulting in a negative water content.

If possible, use a larger sample size to increase the amount of water added to the titration cell with the sample. Furthermore, you should try to reduce the drift value in general. Perhaps the molecular sieve or the septum need to be replaced. You can also use a stabilizing time to make sure the drift is stable before analyzing the sample.

Karl Fischer oven

5.  My samples are not soluble. What can I do?

In case the sample does not dissolve in KF reagents and additional solvents do not increase the solubility of the sample, then gas extraction or the oven technique could be the perfect solution.

The sample is weighed in a headspace vial and closed with a septum cap. Then the vial is placed in the oven and heated to a predefined temperature, leading the sample to release its water. At the same time, a double hollow needle pierces through the septum. A dry carrier gas, usually nitrogen or dried air, flows into the sample vial. Taking the water of the sample with it, the carrier gas flows into the titration cell where the water content determination takes place.

6.  Can all types of samples be analyzed with the oven method?

Many samples can be analyzed with the oven. Whether an application actually works for a sample strongly depends on the sample itself. Of course, there are samples that are not suitable for the oven method, e.g., samples that decompose before releasing the water or that release their water at higher temperatures than the maximum oven temperature.

7.  How do I find the optimal oven temperature for water extraction?

Depending on the instrument used, you can run a temperature gradient of 2 °C/min. This means it is possible to heat a sample from 50 to 250 °C within 100 minutes. The software will then display a curve of water release against temperature (see graph).

From such a curve, the optimal temperature can be determined. Different peaks may show blank, adherent water, different kinds of bound water, or even decomposition of the sample.

This example curve shows the water release of a sample as it has been heated between 130 and 200 °C. At higher temperatures, the drift decreases to a stable and low level.

Generally, you should choose a temperature after the last water release peak (where the drift returns to the base level) but approximately 20 °C below decomposition temperature. Decomposition can be recognized by increasing drift, smoke, or a color change of the sample. In this example, there are no signs of decomposition up to an oven temperature of 250 °C. Therefore, the optimal oven temperature for this sample is 230 °C (250 °C – 20 °C).

In case the instrument you use does not offer the option to run a temperature gradient, you can manually increase the temperature and measure the sample at different temperatures. In an Excel spreadsheet, you can display the curve plotting released water against temperature. If there is a plateau (i.e., a temperature range where you find reproducible water contents), you have found the optimal oven temperature.

8.  What is the highest possible water content that can be measured with a Karl Fischer oven?

Very often, the oven is used in combination with a coulometric titrator. The coulometric titration cell used in an oven system is filled with 150 mL of reagent. Theoretically, this amount of reagent allows for the determination of 1500 mg of water. However, this amount is too high to be determined in one titration and it would lead to very long titration times and negative effects on the results. We recommend that the water content of a single sample (in a vial) should not be higher than 10 mg, ideally around 1000–2000 µg water. For samples with water contents in the higher percentage range, you should consider the combination with a volumetric titrator.

9.  What is the maximum sample size that can be used with the oven? If I use too much sample, will the needle be blocked?

The standard vial for the oven method has a volume of approximately 9 mL. However, we do not recommend filling the vial completely. Do not fill more than 5–6 mL of sample in a vial. We offer the possibility to customize our oven systems, allowing you to use your own vials. Please contact your local Metrohm agency for more information on customized oven systems.

For liquid samples, we recommend using a long needle to lead the gas through the sample. Solid samples and especially samples that melt during analysis require a short needle. The tip of the needle is positioned above the sample material to avoid needle blockage.

Additionally, you should use a «relative blank value», i.e., taking only the remaining air volume into account for blank subtraction. You can find more information about the relative blank and how to calculate it in Application Note AN-K-048.

10.  What is the detection limit of the oven method, and how much sample is required to analyze a sample with 10 ppm (mg/L) water content?

We recommend having at least 50 µg of water in the sample, if analyzed with coulometry. However, if conditions are absolutely perfect (i.e., very low and stable drift plus perfect blank determination), it is possible to determine even lower water contents, down to 20 µg of absolute water. For a sample with a water content of < 10 ppm (mg/L), this would correspond to a sample size of at least 2 g.

11.  How do I verify an oven method?

For the verification of an oven system, you can use a certified water standard for oven systems. With such a standard, you can check the reproducibility and the recovery. There are a few types of standards available for different temperature ranges.

I hope this collected information helps you to answer some of your most burning KF questions. If you have further unanswered questions, do not hesitate to contact your local Metrohm distributor or check out our selection of webinars.

Automate thermal sample preparation

It’s easy with an oven sample changer from Metrohm!

Post written by Michael Margreth, Sr. Product Specialist Titration (Karl Fischer Titration) at Metrohm International Headquarters, Herisau, Switzerland.

Making a better beer with chemistry

Making a better beer with chemistry

Lager or ale? Pale ale or stout? Specialty beer, or basic draft? This week, to celebrate the International Beer Day on Friday, August 7th, I have chosen to write about a subject near and dear to me: how to make a better beer! Like many others, at the beginning of my adult life, I enjoyed the beverage without giving much thought to the vast array of styles and how they differed, beyond the obvious visual and gustatory senses. However, as a chemist with many chemist friends, I was introduced at several points to the world of homebrewing. Eventually, I succumbed.

Back in 2014, my husband and I bought all of the accessories to brew 25 liters (~6.5 gallons) of our own beer at a time. The entire process is controlled by us, from designing a recipe and milling the grains to sanitizing and bottling the finished product. We enjoy being able to develop the exact bitterness, sweetness, mouthfeel, and alcohol content for each batch we brew.

Over the years we have become more serious about this hobby by optimizing the procedure and making various improvements to the setup – including building our own temperature-controlled fermentation fridge managed by software. However, without an automated system, we occasionally run into issues with reproducibility between batches when using the same recipe. This is an issue that every brewer can relate to, no matter the size of their operation.

Working for Metrohm since 2013 has allowed me to have access to different analytical instrumentation in order to check certain quality attributes (e.g., strike water composition, mash pH, bitterness). However, Metrohm can provide much more to those working in the brewing industry. Keep reading to discover how we have improved analysis at the largest brewery in Switzerland.

Are you looking for applications in alcoholic beverages? Check out this selection of FREE Application Notes from Metrohm:

Lagers vs. Ales

There are two primary classes of beer: lagers and ales. The major contrast between the two is the type of yeast used for the fermentation process. Lagers must be fermented at colder temperatures, which lends crisp flavors and low ester formation. However, colder processes take longer, and so fermentation steps can last for some months. Ales have a much more sweet and fruity palate of flavors and are much easier to create than lagers, as the fermentation takes place at warmer temperatures and happens at a much faster rate.

Comparison between the fermentation of lagers and ales.

Diving a bit deeper, there are several styles of beer, from light pilsners and pale ales to porters and black imperial stouts. The variety of colors and flavors depend mostly on the grains used during the mash, which is the initial process of soaking the milled grains at a specific temperature (or range) to modify the starches and sugars for the yeast to be able to digest. The strain of yeast also contributes to the final flavor, whether it is dry, fruity, or even sour. Taking good care of the yeast is one of the most important parts of creating a great tasting beer.

Brewing terminology

  • Malting: process of germinating and kilning barley to produce usable sugars in the grain
  • Milling: act of grinding the grains to increase surface area and optimize extraction of sugars
  • Mashing: releasing malt sugars by soaking the milled grains in (hot) water, providing wort
  • Wort: the solution of extracted grain sugars
  • Lautering: process of clarifying wort after mashing
  • Sparging: rinsing the used grains to extract the last amount of malt sugars
  • Boiling: clarified wort is boiled, accomplishing sterilization (hops are added in this step)
  • Cooling: wort must be cooled well below body temperature (37 °C) as quickly as possible to avoid infection
  • Pitching: prepared yeast (dry or slurry) is added to the cooled brewed wort, oxygen is introduced
  • Fermenting: the process whereby yeast consumes simple sugars and excretes ethanol and CO2 as major products

Ingredients for a proper beer

These days, beer can contain several different ingredients and still adhere to a style. Barley, oats, wheat, rye, fruit, honey, spices, hops, yeast, water, and more are all components of our contemporary beer culture. However, in Bavaria during the 1500’s, the rules were much more strict. A purity law known as the Reinheitsgebot (1516) stated that beer must only be produced with water, barley, and hops. Any other adjuncts were not allowed, which meant that other grains such as rye and wheat were forbidden to be used in the brewing process. We all know how seriously the Germans take their beer – you only need to visit the Oktoberfest once to understand!

Determination of the bitterness compounds in hops, known as «alpha acids», can be easily determined with Metrohm instrumentation. Check out our brochure for more information:

You may have noticed that yeast was not one of the few ingredients mentioned in the purity law, however it was still essential for the brewing process. The yeast was just harvested at the end of each batch and added into the next, and its propagation from the fermentation process always ensured there was enough at the end each time. Ensuring the health of the yeast is integral to fermentation and the quality of the final product. With proper nutrients, oxygen levels, stable temperatures, and a supply of simple digestible sugars, alcohol contents up to 25% (and even beyond) can be achieved with some yeast strains without distillation (through heating or freezing, as for eisbocks).

Improved quality with analytical testing

Good beers do not make themselves. For larger brewing operations, which rely on consistency in quality and flavor between large batch volumes as well as across different countries, comprehensive analytical testing is the key to success.

Metrohm is well-equipped for this task, offering many solutions for breweries large and small.

Don’t take it from me – listen to one of our customers, Jules Wyss, manager of the Quality Assurance laboratory at Feldschlösschen brewery, the largest brewery in Switzerland.

«I have decided to go with Metrohm, because they are the only ones who are up to such a job at all. They share with us their huge know-how.

I can’t think of any other supplier who would have been able to help me in the same way

Jules Wyss

Manager Quality Assurance Laboratory, Feldschlösschen Getränke AG

Previous solutions failed

For a long time, Jules determined the quality parameters in his beer samples using separate analysis systems: a titrator, HPLC system, alcohol measuring device, and a density meter. These separate measurements involved a huge amount of work: not only the analyses themselves, but also the documentation and archiving of the results all had to be handled separately. Furthermore, Jules often had to contend with unreliable results – depending on the measurement procedure, he had to analyze one sample up to three times in order to obtain an accurate result.

A tailor-made system for Feldschlösschen

Jules’ close collaboration with Metrohm has produced a system that takes care of the majority of the necessary measurements. According to Jules, the system can determine around 90% of the parameters he needs to measure. Jules’ new analysis system combines various analysis techniques: ion chromatography and titration from Metrohm as well as alcohol, density, and color measurement from another manufacturer. They are all controlled by the tiamo titration software. This means that bitterness, citric acid, pH value, alcohol content, density, and color can all be determined by executing a single method in tiamo.

Measurement of the overall water quality as well as downstream analysis of the sanitization process on the bottling line is also possible with Metrohm’s line of Process Analysis instrumentation.

Integrated analytical systems with automated capabilities allow for a «plug and play» determination of a variety of quality parameters for QA/QC analysts in the brewing industry. Sample analysis is streamlined and simplified, and throughput is increased via the automation of time-consuming preparative and data collection steps, which also reduces the chance of human error.

Something to celebrate: The Metrohm 6-pack (2018)

In 2018, Metrohm celebrated its 75 year Jubilee. At this time, I decided to combine my experience as a laboratory analyst as well as a marketing manager to brew a series of six different styles of beer for the company, as a giveaway for customers of our Metrohm Process Analytics brand, for whom I worked at the time. Each batch was brewed to contain precisely 7.5% ABV (alcohol by volume), to resonate with the 75 year anniversary. The array of ales was designed to appeal to a broad audience, featuring a stout, porter, brown ale, red ale, hefeweizen, and an India pale ale (IPA). Each style requires different actions especially during the mashing process, based on the type of grains used and the desired outcome (e.g., flavor balance, mouthfeel, alcohol content).

Bespoke bottle caps featuring the Metrohm logo.
The 6 styles of beers brewed as a special customer giveaway to celebrate the Metrohm 75 year Jubilee.

Using a Metrohm Ion Chromatograph, I analyzed my home tap water for concentrations of major cations and anions to ensure no extra salts were needed to adjust it prior to mashing. After some of the beers were prepared, I tested my colleagues at Metrohm International Headquarters in the IC department, to see if they could determine the difference between two bottles with different ingredients:

Overlaid chromatograms from IC organic acid analysis highlighting the differences between 2 styles of the Metrohm 75 year Jubilee beers.

The IC analysis of organic acids and anions showed a clear difference between the beers, allowing them to determine which sample corresponded to which style, since I did not label them prior to shipping the bottles for analysis. As the milk stout contained added lactose, this peak was very pronounced and a perfect indicator to use.

Metrohm ion chromatography, along with titration, NIRS, and other techniques, allows for reliable, comprehensive beer analysis for all.

In conclusion, I wish you a very happy International Beer Day this Friday. Hopefully this article has illuminated the various ways that beer and other alcoholic beverages can be analytically tested for quality control parameters and more  fast, easy, and reliably with Metrohm instrumentation.

For more information about the beer quality parameters measured at Feldschlösschen brewery, take a look at our article: «In the kingdom of beer The largest brewery in Switzerland gets a made-to-measure system». Cheers!

Read the full article:

«In the kingdom of beer – The largest brewery in Switzerland gets a made-to-measure system»

Post written by Dr. Alyson Lanciki, Scientific Editor (and «chief brewing officer») at Metrohm International Headquarters, Herisau, Switzerland.