Chemical compounds, which include ester-, azomethine-, (amide) bonds, silyl groups and ketals/acetals (strong acid medium) can be decomposed in (concentrated) acids (low pH) or bases (high pH). Isocyanates are sensitive toward a lot of nucleophiles including alcohols, amines and water.

Yes, that is right. Above mentioned method is one of the standard methods in defining the stability of the compound or a formulation. Another things you could do is to simply prepare 2-3 different formulations of identical strength and consistency and then store one at a room temperature conditions, the other in the fridge and 3d in the freezer or something similar. Have them tested all after various conditions at set intervals (1, 4, 8 and 12 weeks) to see if there is any difference in composition, appearance, etc. Use analytical techniques, including IR spectrometry (for organic), or mass spectrometry and coloidometry.

Run a two dimesional TLC. it quick and easy!!!

Dear Ahmed,

Yes the structure of an organic compund carry clues about its stability. If you cannot find anything about the stability of your compound in reference sources or litreature, e.g if it is a new compound,please identify the functional groups it carries and look at chemical properties of each. This may help you to make some predictions. Generally most organic compounds are stable in common organic solvents regadless of functional groups, water, acidic or basic solutions or buffers may cause degradation e.g hydrolyse esters depending on their structural properties.

I recommend you trial-error.method if you have enough material. Try to solubilize your compound and check whether it degrades or not by tlc or hplc.. Good Luck!

From the chemical structure of a compound, one could spot out the active functional groups at the same time you could easily identify the reactivity site(s) of your solvent. Now, ask yourself Do they match? if yes then you should take care adding them together for long time or heat. Taking melting point of your compound which shows that it melts with decomposition, indicates that you should not use solvent boils above the melting point of your compound [if you have to heat to solubility].

Very recent article dealing with this topic see:

---An Expert System To Predict the Forced Degradation of Organic Molecules; Alexis D. C. Parenty , William G. Button , and Martin A. Ott * (Lhasa Limited, 22-23 Blenheim Terrace, Woodhouse Lane, Leeds, LS2 9HD, United Kingdom)

Mol. Pharmaceutics, 2013, 10 (8), pp 2962–2974

Good luck

thank u al

Dear Victor Fedoseev, I can not do that because I am working on with very expensive compound.

Dear Anton Kolosov. I am not asking about the stability of the formulation I am talking about solubility which completely different from ur answer.

Dear Akgul Yesilada,

well said. I will do what u said.

Dear Adel Amer, I am amazed from ur sentence ""one could spot out the active functional groups at the same time you could easily identify the reactivity site(s) of your solvent."""

Can you explain more about reactivity site of solvent ?

Chemical compounds, which include ester-, azomethine-, (amide) bonds, silyl groups and ketals/acetals (strong acid medium) can be decomposed in (concentrated) acids (low pH) or bases (high pH). Isocyanates are sensitive toward a lot of nucleophiles including alcohols, amines and water.

Dear Ahmed, I was coming to answer you back when I saw Akgul Yesilada and Albrecht Berg's answers. Well, looking for water or alcohols as solvents with an oxygen atom carrying two lone pair of electrons as nucleophiles (active site) where isocyanates [active functional group] are senstive to such sites. Hope you got it now?

Beside TLC or HPLC you may follow the stability by running 1H-NMR at different time intervals.

Best wishes

You can perform TLC for samples taken from the solution at regular intervals, any new spot indicates the presence of new product, then you can perform IR and NMR for it. You can use preparative TLC plates, so you extract the new product directly from the plate.

I agree with the recommendations of A.Berg and A.Amer. But if you want further contribution I think we need more information about your compound and aim of the study. For example is your compound a macro molecule or small molecule? Is it natural, synthetic or biotechnogical product?.Is it new or known? v.b.

It is just an additional step I will use DSC technique.

Structures that contain ester and amide functional groups are usually subject to acidic and basic hydrolytic degradation in aqueous solutions. The rate of such is higher in instances where you have to warm the sample to achieve full solubility

I support Rajani.

Hi Ahmed, you just need to run 2D TLC its an easy way to monitor the stability of any compound especially if this compound is acid or base sensitive.

There are new set of instruments like FTIR and Mass which will analyze solid compounds directly, you may analyse using these instruments.

I agree with all the answers. TLC is the simplest and cost effective way to determine if the compound is undergoing degradation. First you have to determine appropriate solvent system to monitor your compound on TLC. If your compound has aromatic rings, it will be UV active which is easy to track. Otherwise you may have to using staining solutions to track your compound (iodine chamber, acidified KMnO4 solution to mention a few). One thing to note is that for TLC measurements, first of all you have to ensure that your compound is pure and doesn't contain impurities which might interfere.

I agree with all the colleagues opinion. but in solubility tests you can monitored the physical and chemical changes for your sample like temp. , color , transparency ....etc. after that you can take it ( your sample and check it by hplc techniques with your reference.

Hello Ahmad,

I am new to this forum so forgive me in advance if the questions have been asked and answered.

Can you describe the system a bit more? If I followed Akgul below, it appears she has asked this. JMD

Hello Ahmad,

By stability indicating HPLC analysis we can Identify the degradation of a compound.The degradation compounds can also be quantifed if we have the reference compound with us.

If I understand the question properly, you are not looking to detect degradation (which any analytical method will) but predict degradation via solvent. This is essentially a solvolysis reaction (assuming no acid/base additive) and using the general rules of organic chemistry, one can predict which functional groups would be problematic. For example, reactive groups like acrylates, primary alkyl iodides and acid chlorides may have problems in water solutions. However, there are some acid chlorides that are not as reactive to water as you would think - so like everything, be cautious with your prediction.

With spectral information of FTIR after and later you can view changes in molecular structure.

I still insist that the question does not have to do with any method per se but rather with ingenious prediction based on sound theoretical knowledge of effects of some groups on physico-chemical properties of compounds that bear upon their solubility, in which case I affirm my previous answer and agree with the second part of Kalyan Sethi answer- sound theoretical knowledge of known effects of functional groups on hydrophobic and hydrophilic properties of the compound under study, with regard to how they affect chemical stability of the compound. For example, if you are studying the aqueous solubility of an amide or an ester compound and you are aware of its susceptibility to hydrolytic cleavage catalysed by acidic/basic medium, this will help you take precautions and also predict degradation products. Solubility data from solubility studies on a compound accompanied by degradation is not useful scientifically, because the recorded solubility might be due to the new product

Molecular structure of a compound depicts bonding pattern and presence of functional groups. It can give a vague idea about its solubility and its status (disintegration) in solution. Functional groups that influence physicochemical properties and reactivity of compounds may provide indication for their response to solvolysis reaction with different types of solvents including hydrophobic and hydrophilic solvents.

From the structure of the compound one could predict degradation of it by the solvents if it contains labile functional groups prone to solvolysis. Of course steric and electronic factors may have some influence on degradation on sovolysis.

Dear Ahmed,

The first thing to do is to look for more information in the literature on stress degradation studies of your compound. If no information is available, you can go through the analysis your compound by HPLC analysis at the end of the solubility test. If you have more than one peek comparatively to the freshly prepared compound. This is probably due to the product dégradation of your compoud in the medium studied.

If the degradation is slow enough, you can use HPLC, NMR, IR, TLC (especially 2D TLC), MS, EPR, sometimes UV-VIS... But if the decomposition is very fast, you need to use more advanced techniques. Make a few experiments: dissolve the compound in a few different type of solvent (aprotic/protic, polar/nonpolar, dipolar aprotic, always use very pure, dry, degassed, acid and/or base less solvents) e.g. THF, DMF, DMSO, CHCl3, hexane, benzene... Since I don't know what is your compound I can't say which ones are suitable. Sometimes it might be good to try also water, water+HCl, water+NaOH, MeOH, pyridine, AcOH... When you manipulate with the compound, solvents and solutions - do everything under Ar. Perform as many analysis as you can in each solvent - you should be able to find some solvent in which the compound is stable. In some extreme cases you need to work even in very low temperatures (liquid N) and in sealed (one piece of glass - no joints) Ar line. After you find the solvent in which the compound is stable you can compare all other solvents.

I wish you a stable compounds.

Good luck.