Mr. Baroudi,

The ISO17025 is standard for callibration of the analytical instrumentation. Validation is term used to the field of the ''Analytical Chemistry,'' which means that the method that you have developed produces highly precise, selective, sensitive and accurate analytical information by means of already callibrated analytical instrumentation.

Toward application of NMR for quantitative purposes, this method, in general is inaplicable to microcomponents, trace components and multi-component systems; further, it operates at high concetration LODs; as well as there is significant error contribution, due to mathematical data-processing of the experimental NMR patterns.

Simply, speaking your quantitative protocols, despite that they are validated and based on callibrated NMR instrumentation are not reliable from the perspective of the chemometrics and the ''Analytical Chemistry.''

They do not provide reliable analytical information which can be treated as property of physical evidence, looking at your affiliation.

The best currently developed quantitative analytical instrumentation is the mass spectrometry. The methods of the mass spectrometry provide only exact analytical information and show superior instrumental characteristics (Consider references [61-84] shown in our work [2] to discussion [A] presented, below.)

Despite, the currently approved by the European Union Directives (2002/657/EC; Official J. Eur. Commun. L 221/8, 17.8.2002) analytical protocols for quantification by mass spectrometry, operate at lower capability of the method, thus producing a reliability of the data comparable with the fluorescence spectrocopy (at about 98 %.) (Consider detail on reference [2] in discussion [A], below.)

However, our more recently developed quantitative mass spectrometric method and own authored formulas for quantification of the mass spectrometric outcome ''intensity'' within the framework of our stochastic dynamic theory, has shown that the method of mass spectrometry provide absolute (or exact) quantitative and 3D structural information of the analytes in condense phases. Our studies of analytes in mixture at concentration levels of pg.(mL)-1 and ng.(L)-1 show coefficients of linear correlation between the theoretical formulas introduced and written by us (me and my co-author) and the experiment up to /r/ = 1. Our mass spectrometric protocols are validated with corresponding chromatographic experiments. (Consider references [1,3] to discussion [A].)

[A] [https://www.researchgate.net/post/Any_instrument_available_on_the_market_to_replace_the_UA-3_Uranium_analyser]

The corresponding references, contain information about the type of the analytical instrumentation used to our validated protocols.

I hope that you understand what is the difference between the terms ''validation of a method'' and ''callinbration of the analytical instrumentation.'' (Our validated analytical protocols are obtained by means of already callibrated analytical instrumentation.)

Also, our experience (the experience of me and my co-author) with the most advanced currently developed analytical instrumentation is show in discussion [B]. In addition, I should mention that our experience with NMR is accounted for at about 20 000 NMR spectra (at 1000 data published.)

Thus, as I have written to discussion [B] what we have written as comments on the capability of the analytical instrumentation can be regarded as 'expert opinion.'

You understand, I hope that 'Experts' are those persons, who have developed not only optimized and validated new quantitative protocols, but also have written and discovered innovative mathematical models and formulas for quantification and structural analyses, like us (See our completely innovative model formulas in reference [1] to discussion [A] with the corresponding reference section to reference [1].)

[B] [https://www.researchgate.net/post/Sensitivity_Coefficient_in_Uncertainty_Calculations_for_HPLC_assay_method_UV_assay_methods_and_pH_measurement]

The application of our stochastic dynamic mass spectrometric concept to determine the 3D structures of the analytes in mixture exactly has beem reviewed in reference [2] shown in discussion [C].

[C] [https://www.researchgate.net/post/What_is_the_Mechanism_of_a_Wohl_Ziegler_Reaction_with_a_Iodine_Atom]

Since, as I have written above, the discussed innovative mass spectrometric concept and formulas are our, own, authored contributions to the field of the quantitative mass spectrometry, if you have any questions regarding their direct application to the analytical practice, then do not hesitate to ask your questions, herein, and we shall provide to you a comprehensive guideline step-by-step.

The aim of this public discussion is to introduce our innovative quantitative mass spectrometric method not only to the analytical practice, but also to the educational planes of MSc degree strudents of the field of the ''Chemistry,'' explicitly underlying the educational planes of MSc-strudents of the field of the ''Analytical Chemistry.''

Because of, the currently developed MSc-programmes of the latter field are based on a review of available literature data published by other authors and using mainly old classical analytical protocols; including old theoretical models and concepts, respectively. The same is true for the corresponding textbooks to these educational courses, as you could expect.

Simply speaking, currently, the students of the field of the ''Chemistry'' and the ''Analytical Chemistry'' at the Universities of the European Union do not receive the novelty in the field of the 'Analytical chemistry' and the 'Analytical mass spectrometry' as knowledge.

Bojidarka B. Ivanova Your work is impressive and I hope that you will successfully bring it to light. NMR is inherently an insensitive method, there is no point to compare its quantification capabilities (LOD and LOQ) with mass spectrometric methods. However, when the concentrations are high enough I believe that NMR is the method of choice for many applications related to analytical chemistry, for example ''Purity Checks'', where NMR is much more reliable than mass spectrometry as it sees everything, it has no selectivity except the observed nucleus.

Method validation is a vital requirement of ISO 17025 and is defined by the latter as follows: '' The confirmation by examination and the provision of objective evidence that the particular requirements for specific intended use are fulfilled''. And it also defines the method performance parameters that need to be investigated. So I believe that asking about Method validation in ''accordance with ISO17025'' is not wrong and that ISO 17025 is not limited to instrument calibration.

What I am looking for is: The correct analytical approach as to how develop and validate NMR methods for a specific application, let's say screening and structure elucidation of certain chemical families.

Thank you for all the precisions and the definitions you brought.

Mr. Baroudi,

When we are talking about properties of physical evidences, there are not ''beliefs.'' There are accepted only highly accurate, precise, selective and sensitive experimental evidences. Because of, you operate with the so-called 'legislation accuracy,'' not with the 'academic accuracy.'

The 'Academic Science' permits 'belief' in the course of clarifying a theory and hypothesis as well as its exsperimental proof. However, the Legislation Authorities accept only experimental facts and arguments.

I am not surprised why Western Europe has the largest market of drugs. Perhaps, because of, the corresponding respective and responsible Authorities operate with ''beliefs.'' (If you have 800 g sugar and 200 g drug(s) in muxture, which method you shall apply to quantify this mixture? NMR?)

So, there is important to underline, again, that the mathematical data processing of the NMR patterns provides significant error contribution to the experimental quantitative data.

Thus, could you provide experimental NMR spectrum at the concentration LODs of any analyte and we shall carry out a public online quantification of your outcome, thus illustrating how many is the significance of the error of the mathematical data processing of your NMR data?

Ms. Bojidarka,

Good luck promoting your work !

Wish you all the best for the upcoming new year.

Mr. Baroudi,

I would like to thank you for the wishes.

Happy New 2021 Year for you, as well.

Successful work!