On-line LC-MS Method Validation Course 2024-2025: Registration is open!

The ninth edition of the online course LC-MS Method Validation is open for registration (registration link is here)! The course will be offered as a Massive Open On-line Course (MOOC) during November 26, 2024 – February 7, 2025.

This is a practice-oriented on-line course on validation of analytical methods, specifically using liquid chromatography-mass spectrometry (LC-MS) as technique, mostly (but not limited to) using the electrospray (ESI) ion source. The scope of the course is sufficiently broad, so that it will be useful also to chromatography practitioners using other detector types. The course introduces the main concepts and mathematical apparatus of validation, covers the most important method performance parameters and ways of estimating them. More information about the course can be found in Course introduction page.

Participation in the course is free of charge. Receiving digital certificate (in the case of successful completion) is also free of charge. Printed certificate (to be sent by post) is available for a fee of 60 EUR. Registration is possible until the start of the course. The course materials are available from the above address all the time and can be used via web by anyone who wishes to improve the knowledge and skills in analytical method validation (especially when using LC-ESI-MS).

Märt Lõkov – recipient of the IUPAC’s Balarew award!

Märt_Lõkov_in_front_of_pKa_measurement_setup_with_Balarew_awardMärt Lõkov works in our group focusing on investigations of acid-base equilibria – first of all, determination of acidity and basicity constants (pKa values) of molecules – in nonaqueous solutions. This is a core research direction in our group and he is one of the key people in advancing it.

He has made significant contributions to the self-consistent acidity scale and self-consistent basicity scale in acetonitrile, containing pKa values 231 acids and pKaH values of 279 bases, respectively. Because of how these values have measured (“multiple overlapping” relative spectrophotometric measurements), these scales are widely regarded as the most reliable sets of pKa values in acetonitrile. Thus, assembling those scales was to a large extent also a revision of existing pKa values for many compounds and assigning new values to them.

Märt has mastered the art of pKa measurements in nonaqueous media to the highest degree and is right now one of the most skilful people on planet Earth in performing nonaqueous pKa measurements. Besides doing these measurements himself, he has supervised and is supervising numerous master’s and doctoral students who measure pKa values in their degree projects. Thus, indirectly, via the supervised students, his contribution is even larger.

Perhaps the most ambitious endeavour that Märt is now engaged in is a large-scale re-evaluation and revision of pKa values of carboxylic acids in three nonaqueous solvents – acetonitrile, DMSO, dimethylformamide. The analysis of available pKa data that we have carried out in the framework of the IUPAC project 2015-020-2-500 Critical compilation of acid pKa values in polar aprotic solvents reveals that the non-aqueous pKa values available in the literature for this very important compound class are often significantly in error, sometimes by several orders of magnitude. The revision will involve measurements and analysis of literature data. Märt has assembled a group of people involving several students and the expected outcome will be a large amount of high-quality nonaqueous pKa data of carboxylic acids.

These contributions have been noticed by the International Union of Pure and Applied Chemistry (IUPAC) and Märt has been awarded the Balarew Award for an Outstanding Young Scientist working in the field of critical evaluation of solubility and/or related chemical equilibria!

Märt, please accept our warm congratulations!

How to make maximum use of the available pKa data in non-aqueous solvents?

At the recent Balticum Organicum Syntheticum conference Ivo Leito made a presentation titled How to make maximum use of the available pKa data in non-aqueous solvents? (Photo on the left)

The presentation started with how acid and base strengths, typically expressed as pKa values (acids) or pKaH values (bases), depend on solvation of the proton, as well as of the neutral and ionized forms of the acid/base. Every solvent has different solvation properties. Thus, the pKa values for the same acid/base in different solvents are also different (often dramatically different).

In principle, whenever using pKa values for predicting or rationalizing chemical processes, the pKa values determined in the same solvent should be used. In some solvents, e.g. water, DMSO or acetonitrile large bodies of pKa data exist, while in most solvents either very few pKa values are available or none at all. This leads to the frequent need of estimating pKa values in one solvent from the data in other solvent(s) (Picture on the right). An additional consideration is the (often problematic) quality of pKa data in the literature.

When estimating pKa values in one solvent based on the data in another solvent it is important to clearly define the aim. Is it needed to have the absolute pKa value or is it rather necessary to have the acidity/basicity differences (or acidity/basicity order) within a set of compounds? Perhaps the question is just “can base B deprotonate acid A in solvent S”? If absolute pKa value is needed then what accuracy is necessary? Depending on the aim, there are different possibilities of estimating pKa and pKaH values in a solvent on the basis of data in other solvents.

The presentation gave an overview to what extent such estimates can be usefully done, highlighting both successes and failures, as well as how to recognize clearly erroneous pKa data. The presentation also highlighted the IUPAC project Critical compilation of acid pKa values in polar aprotic solvents that is nearing completion. The critically evaluated pKa data of acids in dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, pyridine, acetone, propylene carbonate, tetrahydrofuran are available from Ivo Leito on request.

The presentation turned out to be highly interesting for the participants, receiving a large amount of questions, which extended well into the coffee break!

From anion-receptor binding constants to a working ion-selective electrode – PhD dissertation of Kerli Martin

On 7th of August, 2024, Kerli Martin successfully defended her PhD dissertation titled Recognition of carboxylates by synthetic receptors – from structure-affinity studies to solid-contact anion-selective electrode prototyping.

This dissertation begins with the observation that while polymer membrane ion-selective electrodes (ISEs) have been well known and widely used for decades to detect small cations, determining organic anions with ISEs remains a challenge, essentially without a solution. The dissertation presents a journey starting with the study of the interactions between small monocarboxylates and numerous anion receptors – potential new ionophores.

By measuring the binding constants of eight carboxylates (formate, acetate, pivalate, lactate, ibuprofen, ketoprofen, glucuronate, and benzoate) to 44 synthetic receptor molecules using nuclear magnetic resonance, Kerli constructed eight binding affinity scales where all the binding affinities are comparable. These results were then assembled into a large overall map of the receptor-anion binding constants (Figure on the right). The results revealed that the selected synthetic hydrogen-bond donor receptors can distinguish between carboxylates with different structures.

As a result of this binding study, a 1,3-bis(carbazolyl)urea derivative (receptor 13 in the Figure on the right) was selected as the hydrogen-bonding ionophore to create prototypes of ion-selective electrodes that can detect acetate. The electrodes built by Kerli displayed a unique selectivity pattern for different anions. The addition of this ionophore to the electrode membrane significantly (by up to several orders of magnitude) reduced the interference from other common ions such as chloride, bromide and nitrate. Kerli’s work is an important step forward in designing ionophores that can specifically bind carboxylates and building sensitive and selective ion-selective electrodes for different anions.

The defence procedure itself was quite a battle for Kerli! It started with the detailed questioning by the opponent prof. Claudia Caltagirone (University of Cagliari, Italy) on all the aspects of the thesis. Particularly interesting and difficult were some of her highly technical questions regarding the fluorescence measurement of binding affinities. Then there was a long string of questions from the defence committee members. The topics of Kerli’s thesis ranged from receptor-anion binding to computational chemistry and from materials science to hard-core electrochemistry. Thus, most committee members found something familiar and worth asking about. Kerli managed nicely with all the questions and left a very good impression on everybody in the room!

Please accept our warm congratulations, Kerli!

LC-MS Validation online course 8th run has finished!

On February 8, 2024 the on-line course (MOOC) LC-MS Method Validation offered by the University of Tartu finished successfully.

Eventually, altogether 1014 people registered from 109 countries. Around half of them, 508 participants actually started the course (i.e. tried at least one graded test at least once) and out of them 311 successfully completed the course. The overall completion rate was 31%. The completion rate of participants who started the studies was 61%. The completion rates of active participants (i.e. who started the course) seems to have stabilized at around 60%, which can be considered good. In addition, the overall completion rate is starting to increase again. In any case, there is some food for thought for us on how we could improve the overall completion rate…

LC-MS Validation online course 8th run has finished

At the same time, those participants who actually took part in the course, were very active and asked lots of questions. The questions were often very much to the point and addressed things that are really important to analysts in their everyday work. The course has several forums (general and by topic) and during the course period the overall number of forum posts was above 400 (!) (overall number of posts, both from participants and from teachers) and the forums are still active and posts are still coming in.

This active participation made teaching of this MOOC a great experience also for us, the teachers. The discussion threads gave a lot of added value to the course and some of them triggered making important modifications to the course materials, even during the course. Importantly, thanks to active participants, several mistakes were found and corrected in the course materials. As a result, the overall quality of the course improved.

We want to thank all participants for helping to make this course a success!

We plan to repeat this course again in Autumn 2024.

Measurement Uncertainty online course, March 19 – May 2, 2024: Registration is open!

The 2024 edition of the web course (MOOC) Estimation of Measurement Uncertainty in Chemical Analysis will be running from March 19 to May 2, 2024. Registration is now open!

The full course material (as well as the registration link) is accessible from the web page. The course materials include videos, schemes, calculation files, and numerous self-tests (among them also full-fledged measurement uncertainty calculation exercises) and examples. Almost all areas of analytical chemistry are addressed, ranging from simple volumetric operations and titrations to sophisticated instrumental analysis, such as determining pesticide residues by LC-MS. Efforts are made in the course to address also such uncertainty sources encountered in chemical analysis that are difficult to quantify, e.g. uncertainty due to possible interference effects (incomplete selectivity), analyte losses, etc.

In order to pass the course, the registered participants have to take six graded tests and get a higher than 50% score in every graded test. These tests are available to registered participants via the Moodle e-learning platform.

Participants who successfully pass the course will get a certificate from the University of Tartu. A digital certificate of completion is free of charge. A certificate of completion on paper can be requested for a fee of 60 euros.

You are welcome to distribute this message to potentially interested people!

 

On-line LC-MS Method Validation Course 2023-2024: Registration is open!

The eighth edition of the online course LC-MS Method Validation is open for registration (registration link is here)! The course will be offered as a Massive Open On-line Course (MOOC) during Nov 21, 2024 – Feb 02, 2024.

This is a practice-oriented on-line course on validation of analytical methods, specifically using liquid chromatography-mass spectrometry (LC-MS) as technique, mostly (but not limited to) using the electrospray (ESI) ion source. The scope of the course is sufficiently broad, so that it will be useful also to chromatography practitioners using other detector types. The course introduces the main concepts and mathematical apparatus of validation, covers the most important method performance parameters and ways of estimating them. More information about the course can be found in Course introduction page.

Participation in the course is free of charge. Receiving digital certificate (in the case of successful completion) is also free of charge. Printed certificate (to be sent by post) is available for a fee of 60 EUR. Registration is possible until the start of the course. The course materials are available from the above address all the time and can be used via web by anyone who wishes to improve the knowledge and skills in analytical method validation (especially when using LC-ESI-MS).

We are also glad to announce, that the course has been added into the BIPM (Bureau International des Poids et Mesures) e-learning platform. The BIPM is the most important international metrology organization established by the Metre Convention, through which Member States act together on matters related to measurement science and measurement standards. BIPM is also the home of the International System of Units (SI) and the international reference time scale (UTC). The Institute of Chemistry of University of Tartu is a designated institute by the BIPM since 2010.

Dr. Andre Leesment – PhD thesis on the acidity in biphasic systems and gas-phase

Last Friday, June 9th, 2023, Andre Leesment successfully defended his PhD thesis titled Quantitative studies of Brønsted acidity in biphasic systems and gas-phase. The opponent was Prof. Kiyohiko Sugano from the Ritsumeikan University, Japan.

Dr. Andre Leesment (on the right) after his PhD defence with his supervisor Prof. Ivo Leito (on the left).

Experiments for measuring acidity of medicines, catalysts, and other chemicals are almost always performed under monophasic conditions. However, many of them are lipophilic compounds, and in biphasic systems they prefer the nonpolar organic phase, where their properties are much different from their properties in an aqueous phase. Yet the interactions with the organic phase are completely ignored in a typical acidity measurement. It’s like seeing only half of the picture. Why is such an incomplete approach being used for something this important?

Until recently, there was no theoretical basis or experimental method to conduct measurements of acidity under more relevant conditions. Andre’s PhD thesis focuses on providing the tools to measure acidity, and by extension, many other properties of molecules in biphasic systems in a more realistic and accurate way. Hopefully, these tools lead to a more effective drug development, catalyst research, etc.

Congratulations to you, Andre!  

 

LC-MS Validation online course 7th run has finished!

On February 10, 2023 the on-line course (MOOC) LC-MS Method Validation offered by the University of Tartu finished successfully.

Eventually, altogether 903 people registered from 104 countries. Less than half, 376 participants actually started the course (i.e. tried at least one graded test at least once) and out of them 218 successfully completed the course. The overall completion rate was 24%. The completion rate of participants who started the studies was 58%. The completion rates of active participants (i.e. who started the course) seems to have stabilized not too far from 60%, which can be considered good. However, the overall completion rate is still in decline (although there is no statistically significant difference between the 25% and 24% of the last two editions). In any case, there is some food for thought for us on how we could improve the overall completion rate…

At the same time, those participants who actually took part in the course, were very active and asked lots of questions. The questions were often very much to the point and addressed things that are really important to analysts in their everyday work. The course has several forums (general and by topic) and during the course period the overall number of forum posts was above 400 (!) (overall number of posts, both from participants and from teachers) and the forums are still active and posts are still coming in.

This active participation made teaching of this MOOC a great experience also for us, the teachers. The discussion threads gave a lot of added value to the course and some of them triggered making important modifications to the course materials, even during the course. Importantly, thanks to active participants, several mistakes were found and corrected in the course materials. As a result, the overall quality of the course improved.

We want to thank all participants for helping to make this course a success!

We plan to repeat this course again in Autumn 2023.

LC-MS Method Validation web course: 904 participants from 104 countries!

On Tuesday, November 22, 2022 the web course LC-MS Method Validation was launched for the fifth time as a MOOC (Massive Online Open Course). There are 904 registered participants (the largest number ever in this course) from 104 countries, ranging from Sudan to Suriname and from Malaysia to Macedonia. Image on the left shows the countries where the participants come from.

This is a practice-oriented on-line course on validation of analytical methods, specifically using LC-MS as technique. The course introduces the main concepts and mathematical apparatus of validation, covers the most important method performance parameters and ways of estimating them. The LC-MS validation course is delivered by a team of 7 teachers, each with their own specific area of competence. This way it is expected to offer the best possible knowledge in all the different subtopics of analytical method validation.

The full set of course materials is accessible from the web page https://sisu.ut.ee/lcms_method_validation/. The course materials include videos, schemes, calculation files and numerous self-tests (among them also full-fledged calculation exercises). In order to pass the course, the registered participants have to take all tests and get higher than 50% score from each of them. These tests are available to registered participants via the Moodle e-learning platform. Participants who successfully pass the course will get a certificate from the University of Tartu.