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The importance of titrations in pharmaceutical analysis

The importance of titrations in pharmaceutical analysis

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

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

Applicability of modern titration methods in pharmaceutical analysis

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

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

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

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

Automated titration procedure

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

 

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

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

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

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

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

Choice of electrodes for pharmaceutical titrations

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

Download our free brochure to learn more.

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

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

Type of titration Electrode Close-up view Pharma Application / API

Aqueous acid/base titrations

e.g. titrant is NaOH or HCl

phenolphthalein indicator

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

e.g. Ecotrode Plus, Unitrode

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

API: Benzbromaron, Potassium carbonate, Potassium bicarbonate

Non-aqueous acid/base titrations

e.g. solvent is organic or glacial acetic acid

crystal violet indicator

Combined pH electrode with alcoholic reference electrolyte LiCl in EtOH

e.g. Solvotrode easyClean

Water-insoluble weak acids and bases

Assay of API

Acid value (free fatty acids)

API: Caffeine, Ketoconazole

Redox titrations

e.g. titrant is sodium thiosulfate

starch indicator

Pt metal electrode

e.g. combined Pt ring electrode, Pt Titrode

 

Antibiotic assays

Peroxide value in fats and oils

API: Captropril, Paracetamol, Sulfonamide

Precipitation titrations

e.g. titrant is silver nitrate

ferric ammonium sulfate indicator

Ag metal electrode

e.g. combined Ag ring electrode, Ag Titrode

Chloride content in pharmaceutical products

Iodide in oral solutions

API: Dimenhydrinate

Complexometric titrations

e.g. titrant is EDTA

hydroxy naphthol blue indicator

Ion-selective electrode

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

Calcium content in pharmaceutical products

API: Calcium succinate

Photometric titration

e.g. titrant is EDTA

Eriochrome black T indicator

Photometric sensor

e.g. Optrode

Assay of various metal salts in APIs

API: Chondroitin sulfate, Bismuth nitrate, Zinc sulfate

Table 1. Electrode guide for pharmaceutical titrations.

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

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

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

Conclusion

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

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

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

Need a reason to switch

from manual to automated titration?

How about FIVE?

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

NIR spectroscopy in the polymer industry: The ideal tool for QC and product screening – Part 1

NIR spectroscopy in the polymer industry: The ideal tool for QC and product screening – Part 1

Undoubtedly, there is a trend nowadays towards stricter quality assurance and quality control in production processes, such as in the polymer industry. At the same time, this trend is accompanied by a stronger focus on cost-saving and time-efficient methods so that performing more testing will not automatically result in higher costs. 

Major driving factors for companies to voluntarily implement more testing and quality practices include: 

  • Cost pressure. Testing can reveal out-of-specification products, allowing production to be stopped in plenty of time, eliminating excess manufacturing costs.
  • Increased competition. Quality practices provide a competitive edge and can be used as a marketing tool to raise brand value.
  • Scarcity of resources. Qualified staff are difficult to find; therefore, checks that can be carried out by non-specialists are invaluable.

Near-infrared (NIR) spectroscopy is an analytical method that addresses the above drivers and is particularly suited for making quality control more efficient and cost-effective as shown in this article. A short overview of NIRS is presented, followed by application examples for the quality control of polymers, concluding with indications and examples regarding how polymer producing and processing companies can benefit from the utilization of NIRS.

NIR technology overview

The interaction between light and matter is a well-known process—just recall the last time your skin was sunburned. Depending on the applied light intensity and energy, the interaction can be destructive (as with a sunburn) or harmless (like radio waves). Light used in spectroscopic methods is typically not described by the applied energy, but in many cases by the wavelength or wavenumbers.

A NIR spectrometer such as the Metrohm DS2500 Polymer Analyzer measures this interaction between light and matter to generate spectra as displayed in Figure 1. NIRS is especially sensitive to the presence of certain functional groups including -CH, -NH, -OH, and -SH. Therefore, NIR spectroscopy is an ideal method to quantify chemical parameters like water content (moisture), hydroxyl value, acid number, and amine content, just to name a few. Furthermore, the interaction is also dependent upon the matrix of the sample itself, which allows the detection of physical and rheological parameters like density, intrinsic viscosity, and melt flow rate.

Figure 1. Nylon and polyethylene spectra resulting from the interaction of NIR light with the respective samples.

All this information is contained in just one spectrum, making this method suitable for quick multiparameter analysis. Solid samples, such as powders, are secured within an appropriate container or vial (Figure 2a) then placed as-is on the analyzer. Heterogeneous samples, such as polymer pellets, can be analyzed using larger measurement cups (Figure 2b).

Figure 2. Solid sample placement for NIR spectra measurement. A) Direct measurement of powders in a vial. B) Large heterogeneous sample such as pellets can be analyzed using large sample cups.

Learn more about the DS2500 Polymer Analyzer on our website!

The measuring mode is referred to as «diffuse reflection», generally an appropriate procedure for analyzing granules, fibers, flakes, and both coarse and fine powders. For diffuse reflection (Figure 3), the NIR light comes from below the sample, penetrating and interacting with it, while being partially absorbed. Unabsorbed NIR light reflects to the detector. In less than 1 minute, the measurement is completed, and the results are displayed.

Figure 3. Schematic display of the light path interacting with a sample during diffuse reflection.

The procedure to obtain NIR spectra already highlights two major advantages of NIR spectroscopy: simplicity regarding sample measurement and speed.

  • Fast technique with results in less than a minute.
  • No sample preparation required – measure sample as-is.
  • Low cost per sample – no chemicals or solvents needed.
  • Environmentally friendly technique – no waste generated.
  • Non-destructive – precious samples can be reused after analysis.
  • Easy to operate – inexperienced users are immediately successful.
Read our previous blog posts to learn more about NIRS as a secondary technique.

What kinds of polymer manufacturers in the production chain might benefit from using NIR spectroscopy?

Figure 4 illustrates the individual production steps from the plastic producer, via plastic compounder and plastic converter to the plastic parts producer. The first step in which near-infrared lab instruments can be used is when pure polymers are produced, and their purity requires confirmation. NIRS is also a very useful technique for the next step, when polymers are compounded into products to be used for further processing. 

Figure 4. Simplified illustration of the polymer production chain.

A plastic part producer, typically an injection molding or extrusion company, assesses the quality of the received polymer batches. In many cases, the certificate from the supplier is trusted without any further verification. However, a rapidly growing number of companies that create products for the medical industry or that produce parts of high value or in high quantities have started to assess the important rheological quality parameters of each polymer batch before using it for injection molding or extrusion. Feeding an out-of-specification polymer to the production process leads to costly standstill of the equipment and its time-consuming cleaning.

Here, a quick pre-check of the starting polymer material used in the process would be ideal to avoid such risks and potential downtime. For this purpose, NIRS is the ideal solution because it is fast, has low running costs, and can be operated by personnel without any extensive chemical education.

When the final part is created at the end of the production process, it can also be subjected to NIR spectroscopic investigations for quality control. This is useful for assessing the homogeneity or thickness of bottles or sheets of material, for example.

What kinds of polymer applications and parameters are possible with NIRS in general?

In principle, NIRS analysis is more suitable for measuring bulk materials and not for trace analysis. Furthermore, polymer samples should contain no more than 3% carbon black and a reference method should be available. When complying with these prerequisites, NIR spectroscopy can be used as a fast and cost-saving alternative measurement technology.

Metrohm Application Bulletin 414 describes several applications for the polymer industry that can be carried out with the aid of NIRS instruments. This document contains analyses of a wide range of parameters in a very large array of samples.

Examples for use of NIR spectroscopy for selected polymers are indicated in Table 1.

Table 1. Examples for use of NIRS for selected polymers.
Polymer type Parameter Conventional analysis method Advantage of using NIRS Related NIRS application note
Polyethylene (HDPE/LDPE) Density Densimeter Results within 30 seconds AN-NIR-003
AN-NIR-081
Melt Flow Index MFI apparatus

Time-saving

No cleaning of equipment

AN-NIR-083
Polypropylene (PP) Melt Flow Index MFI apparatus

Time-saving

No cleaning of equipment

AN-NIR-004
AN-NIR-082
AN-NIR-083
Polyamide (PA) Intrinsic Viscosity Ubbelohde viscosimeter

No time-consuming dissolution in hazardous chemicals

No waste

Cost savings

AN-NIR-005
AN-NIR-060
COOH, NH2, Moisture Titration

Time & cost savings

No chemicals needed

No chemically educated operator needed

AN-NIR-077
Polyethylene terephthalate (PET) Intrinsic Viscosity Ubbelohde viscosimeter

No time-consuming dissolution in hazardous chemicals

No waste

Cost savings

AN-NIR-023
Acid number Titration

Time & cost savings

No chemicals needed

No chemically educated operator needed

Isophtalic acid HPLC

No eluent solvents needed

Time & cost savings

No chemically educated operator needed

Polyurethane (PU) OH of polyols Titration

Time & cost savings

No chemicals needed

No chemically educated operator needed

AN-NIR-006
AN-NIR-007
Isocyanate content Titration AN-NIR-035
AN-NIR-065
AN-NIR-068
Polyvinyl Alcohol (PVA) Degree of alcoholysis Titration

Time & cost savings

No chemicals needed

No chemically educated operator needed

AN-NIR-076
Silicone Rubber Vinyl content Gas Chromatography

Time & cost savings

No chemicals needed

No chemically educated operator needed

AN-NIR-084
Polyvinylidene Chloride (PVDC) Sheet thickness Weighing

Time-saving

Reduced user error risk

AN-NIR-092

Save up to 90% on running costs with NIRS

Underestimation of quality control processes is one of the major factors leading to internal and external product failure, which have been reported to cause a loss of turnover between 10–30%. As a result, many different norms are put in place to support manufacturers with their QC process. However, time to result and the associated costs for chemicals can be quite excessive, leading many companies to implement near-infrared spectroscopy in their QC process.

Our free white paper illustrates the potential of NIRS and displays cost saving potentials up to 90%.

Future installments in this series

This article is only a general overview of the use of NIR spectroscopy as the ideal QC tool for the polymer industry. Future installments will be dedicated to the most commonly produced and commercially important polymers and will include much more detailed information. These polymers are:

 

  • Polyethylene and Polypropylene (PE & PP)
  • Polyethylene Phthalate (PET)
  • Polyamide (PA)
  • Polyols and Isocyanates to produce Polyurethane (PU)

For more information

About spectroscopy solutions provided by Metrohm, visit our website!

We offer NIRS for lab, NIRS for process, as well as Raman solutions

Post written by Wim Guns, International Sales Support Spectroscopy at Metrohm International Headquarters, Herisau, Switzerland.

Developing the electrochemical sensors of your dreams

Developing the electrochemical sensors of your dreams

«Measurement is the first step that leads to control and ultimately to improvement. If you can’t measure something, you can’t understand it. If you can’t understand it, you can’t control it. If you can’t control it, you can’t improve it.»
H. James Harrington

 

The statement above relates very well to the demand to measure more and more about our lives—one option available to achieve this improvement is through the development of electrochemical sensors. Sensor manufacturing is in high demand and is expected to grow exponentially in the coming years.

Everything around us gives valuable information, including the chance to discover and the ability to know how we need to act. Developing sensors opens up new opportunities to develop and customize powerful and accurate solutions for specific applications in multiple fields, as well as being able to monitor different parameters outside the laboratory on the spot.

Electrochemical sensors and biosensors that are developed in small sensor strips allow for many measurement and monitoring possibilities. Sensors with new strategies have evolved by working with new materials, substrates, and formats that improve their accuracy, miniaturization, and portability in response to new analytical paradigms in various markets.

Why are electrochemical sensors needed?

Electrochemical sensors are a sensitive, fast, accurate, and cost-effective solution for point-of-care measurements. Such characteristics make these solutions suitable for integration into various monitoring or automation systems which, combined with a data communication structure, can generate considerable advances in the field of biosensing, creating new and important possibilities for the market as practical and future-proof solutions.

The latest advances in the miniaturization of electrochemical sensors is another reason for their growing use and popularity. These portable and simple formats are geared towards the end user—technical and non-technical—to obtain results in their daily work. This makes electrochemistry very attractive to anyone thinking of taking an idea or research to the next level and commercializing their findings.

This progress makes the development of electrochemical sensors one of the most active areas of analytical electrochemistry. These sensors are capable of providing information with superior features such as: real-time data generation, disposability, high accuracy, or wide-range linearity that make these small sensor strips an advanced alternative to conventional, bulky and expensive analytical instruments.

Multiple possibilities for production of electrochemical sensors

Your dream sensor is now possible thanks to expert manufacturing from Metrohm DropSens that allows customization and production according to your required quantity and specifications. Using an innovative and experienced production process, large quantities of customized sensors can be produced while maintaining high product quality and scalability stability as well as an attractive price-performance ratio.

Optimized design

Metrohm DropSens R&D experts understand the application concept in depth. The engineering and design departments assist in the development process to implement a final prototype, always finding a solution in which all specifications converge.

 

Custom-made solutions

The development of these sensors allows their miniaturization while at the same time allowing the possibility of modifications in terms of spatial distribution, shape, area, substrate, or the use of a wide range of materials, to name just a few. In addition, flexible sensors, textile sensors, biosensors or other types of solutions can be manufactured to suit the biochemical and electronic process needs of each individual application.

 

 Manufacture on demand

Take advantage of this capacity to produce custom-made electrochemical sensors on demand efficiently and quickly, regardless of the quantity ordered, meeting future needs without ever running out of supply.

 

High performance market-ready solutions

Be the first to bring a sensor to market, avoiding long processes and an abundance of partners. Count on the fast and professional manufacturing capability from a company positioned directly in the launch and production of electrochemical sensors to the market.

 

The highest quality standards

Production is carried out with the highest quality materials, printing, and finishing. In addition, the solutions are approved by quality management systems, which allows the highest levels of reliability and stability to be achieved in each product, guaranteeing its scalability.

From small-scale prototyping to large-scale sensor production, Metrohm DropSens offers support throughout the entire process: initial conceptualization, in-depth prototype design, and helping to achieve results that meet your goals.

This expert manufacturing is backed by the global support of Metrohm’s extensive worldwide network of partners. With more than 75 years of experience, Metrohm offers the highest standards of product and service quality, providing all you need for chemical analysis support.

Sensors for infinite uses

Progress and improvement cannot be adequately defined without the use of sensors. Everything can be measured (and usually quantified), which gives many opportunities to grow. State-of-the-art sensors based on the most recent scientific accomplishments excel in their customer-friendliness, allowing sensors to become part of everyday life as they are accessible to more people. Furthermore, the development of these decentralized devices can leverage R&D in many different industry sectors by addressing their specific applications and needs, giving them the option to reach the market.

The measurement of human health, pollution, information about foods and beverages, environmental analysis, water contamination, illicit drugs, or viruses, among other things, can be performed with electrochemical techniques and solutions. Sensors also play a fundamental role in industrial sectors such as agriculture and livestock farming, being able to measure an infinite number of parameters applicable to their improvement and development.

Another aspect to be taken into account regarding the development and growth of relevant sectors is the capacity of sensors for continuous electrochemical monitoring of different biomarkers. Combined with automated wireless data communication systems, this has represented a considerable advance in the field of biosensing towards new market possibilities.

Certified by ISO 13485 for the manufacture of sensors for medical devices

In the clinical setting, point-of-care (POC) testing dominates as an end-user application. The main areas of development focus especially on POCs for home monitoring of chronic diseases and POC testing of infectious pathologies, among others.

The COVID-19 pandemic, caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a threat to global public health. Therefore, the development of a rapid, accurate, and easy-to-apply diagnostic system for the detection of the virus has become crucial to control the outbreak of infection and monitor the progression of the disease. 

Metrohm DropSens manufactures electrochemical sensors under ISO 13485 certification, which attests to the ability to provide production that consistently meets customer and regulatory requirements applicable to medical devices and related services.

The sectors of medical and diagnostic services are driven by a strong interest in rapid point-of-care testing and monitoring devices. In addition, the integration of biosensors into medical diagnostic equipment will offer endless opportunities for the market for prevention and control of the spread of disease.

Moreover, the proliferation of biosensors employing electrochemical sensing technology has been gaining ground due to the strong demand for rapid and non-invasive POC applications. These are market-ready sensors that can be used by anyone.

Electrochemical test strips are a suitable canvas and format for the creation of a motorized diagnostic and testing system in this area and can provide a solution to these new analytical paradigms. The development of non-invasive sensors for decentralized and continuous monitoring has received a great deal of attention from researchers in different industries for painless analysis of important health parameters.

These are extraordinary times for sensor development

We constantly look for ways to mark our progress, and having the ability to measure parameters is one way to achieve this. The development of electrochemical sensors opens up a wealth of possibilities, and thanks to the customization and mass production capabilities of Metrohm DropSens, you will be able to produce high quality electrochemical devices that are tailored to specific applications. This production process is designed to meet the long-standing market demand for end-user-oriented sensor solutions with features such as: portability, wireless functionality, and simple usability without any loss in measurement accuracy.

Electrochemical sensors, based on small sensor strips, are now simpler, smarter, more user-oriented, and cheaper than conventional electrodes, which rely on cleaning or recovery tasks and have lower reproducibility in many areas of analysis. These devices are also characterized by the ability to acquire data in real time, which, combined with portability and ubiquitous availability, makes them practical and powerful tools for measurement purposes. In addition, they can provide an alternative solution for applications where complexity is involved, as they can be developed to adapt to infinite specifications.

Electrochemical sensors guarantee optimum quality, excellent measuring accuracy, and use perfectly bonded materials, prints, and substrates. They can be developed in various formats and are reproducible on flexible or even wearable materials, always maintaining good conductivity and preserving the correct alignment of the different sensor elements in all cases.

Metrohm DropSens is able to produce these electrochemical sensors in large quantities on a customized basis while still maintaining all the benefits and features scaled up from the customer-developed application. This is possible while guaranteeing market-ready production, an efficient price-performance ratio, and no risk of stock-outs – always with continuous global and specialized support service. Contact us to make your dream sensor a reality!

Dream of your sensor

and together we will make it true

Post written by Belén Castedo González, Marketing Communication at Metrohm DropSens, Oviedo (Asturias), Spain.

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.

    Easy moisture determination in fertilizers by near-infrared spectroscopy

    Easy moisture determination in fertilizers by near-infrared spectroscopy

    Blooms or bombs?

    As the global population steadily increases, it is important that sufficient crops are produced each year to provide enough food, clothing, and other products. Crops such as corn, wheat, soy, and cotton receive nutrients from the soil they are grown in. Fertilizers play a crucial role in providing these crops with the nutrients they need to grow properly.

    An important ingredient in the production of high quality, effective fertilizers is ammonium nitrate (NH4NO3), a good source of nitrogen and ammonium for plants.

    Produced as small beads similar in appearance to kitchen salt, ammonium nitrate is cheap to buy and usually safe to handle – but storing it can be a problem. Over time, the compound absorbs moisture, which leads to clumping of the individual beads into a larger block. When such a large quantity of compacted ammonium nitrate is exposed to intense heat it can trigger an explosion.

    Over the last century, ammonium nitrate has been involved in at least 30 disasters and terrorist attacks. One of the most recent occurrences was on the evening of August 4th, 2020 in Beirut, where an ammonium nitrate explosion killed at least 220 people and injured more than 5000. This blast is one of the largest industrial disasters ever linked to NH4NO3.

    Moisture analysis methods for fertilizers

    During the production process of ammonium nitrate it is important to control the moisture content. A low moisture content is preferable, but unnecessary excess drying leads to additional manufacturing costs.  Regulations for different fertilizers vary across the globe, but local legal limits ensure that the maximum amount of water present must not be exceeded.  Therefore,  rapid, reliable, and accurate methods for the determination of moisture is necessary. Out of those available, Karl Fischer titration is one of the most common; oven drying, for example, cannot be used with fertilizers containing ammonium nitrate.

    Compared to these methods, near-infrared spectroscopy (NIRS) offers unique advantages. It is a secondary technique that generates reliable results within seconds without needing any sample preparation. NIRS is a non-destructive measurement technique and at the same time does not create any chemical waste.

    Read our previous blog posts below to learn more about NIRS as a secondary technique.

    NIRS analysis of solids

    The most suitable NIR analyzer to measuring different parameters in fertilizer or ammonium nitrate pellets is the Metrohm DS2500 Solid Analyzer with Large Sample Cup.

    Solid samples (e.g., granules and pellets) that are filled in the rotating DS2500 Large Sample Cup must be placed on the analyzer window. While scanning the sample, the Large Sample Cup will rotate in order to compensate for inhomogeneity.

    As the DS2500 Solid Analyzer is a pre-dispersive system, the sample is illuminated with monochromatic light in order to keep the energy level as low as possible. Therefore, the instrument lid must be closed prior to starting the analysis so external light does not affect the results. The NIR radiation comes from below and is partially reflected by the sample to the detector, which is also located below the sample vessel plane. After 45 seconds, the measurement is completed, and a result is displayed. As this reflected light contains all the relevant sample information, this measurement technique is called diffuse reflection.

    Advantages of using NIRS

    The procedure for obtaining the NIR spectrum already highlights its simplicity regarding sample measurement and its speed. Several advantages of NIRS are listed below:

     

    • Fast technique with results in less than 1 minute.
    • No sample preparation required – solids and liquids can be used in pure form.
    • Low cost per sample – no chemicals or solvents needed.
    • Environmentally friendly technique – no waste generated.
    • Non-destructive – precious samples can be reused after analysis.
    • Multiple component analysis – prediction of different constituents in parallel.
    • Easy to operate – inexperienced users are immediately successful.

    Overall, near-infrared spectroscopy is a robust alternative technique for the determination of both chemical and physical parameters in solids and liquids. It is a fast method which can also be successfully implemented for routine analysis by staff without any higher laboratory education.

    Related Applications

    Specialty chemicals have to fulfill multiple quality requirements. One of these quality parameters, which can be found in almost all certificates of analysis and specifications, is the moisture content. The standard method for the determination of moisture content is Karl Fischer titration.

    This method requires reproducible sample preparation, chemicals, and waste disposal. Alternatively, near-infrared spectroscopy can be used for the determination of moisture content. With this technique, samples can be analyzed without any preparation and without using any chemicals.

    More information about the application details can be found below!

    Moisture content is one of the most commonly measured properties of fertilizers. Globally, regulations for different fertilizers vary, but local legal limits ensure that the maximum amount of water must not be exceeded. A number of analytical techniques are available for this purpose. Next to gravimetric methods, Karl Fischer titration is often used for accurate moisture determination.

    Compared to these methods, near-infrared spectroscopy offers unique advantages: it generates reliable results within seconds, and at the same time does not create chemical waste. This Application Note explains how NIRS can offer fast, reagent-free analysis of moisture content in various fertilizer products.

    Read on for more technical details…

    To learn more about how Karl Fischer titration and NIRS complement each other for the analysis of moisture in different products, read our blog post!

    For more information

    About spectroscopy solutions provided by Metrohm, visit our website!

    We offer NIRS for lab, NIRS for process, as well as Raman solutions

    Post written by Wim Guns, International Sales Support Spectroscopy at Metrohm International Headquarters, Herisau, Switzerland.