[sociablepsych]

Hi,

I'm new to these forums and was wondering if anyone would offer their advice/opinion on a topic that I am doing a research paper over for a psychoactive drugs course.  First, I do not have a strong background in chemistry so I am relearning things I have forgotten over the past years.  Ok, so I am researching into the effects of a street drug named "Krokodil;" some of you have probably heard of it and its effects on drug users.  The drug is made from various over-the-counter chemicals and is never quite the same (depending on how it is cooked, what is put in, etc...).  Most people know the drug as a morphine derivative called desomorphine (or dihydrodesoxymorphine-D).  Although other impurities exist in the drug, another compound has been identified through gas-chromotography to be trifluoroacetyl & trimethylsilyl derivatives of desomorphine. 

I'm highly interested in the drug's corrosive effects on skin and organs so trifluoroacetyl seems to be the culprit, either in its trifluoroacetate structure or trifluoroacetyle chloride structure (both of these compounds are highly corrosive to skin).  My question is this, if the trifluoroacetyl stays attached to desomorphine, is it possible that it carries over its corrosive effects into the body or does it take on new properties?

Also, I was unsure if this should go into the organic chemistry section or here, but since it is a biological question as well, I decided to post here.  Thank you for any help.

[Babcock_Hall]

My answer consists of educated guesses.  First, it is often the case that to make compounds volatile enough for gas chromatography, one has to make derivatives.  Trimethylsilyl groups used to be a common way to derivatize hydroxyl groups (maybe this is still true).  In other words, I am not sure that either of these groups is actually present in the drug itself.  I did a quick search and found that there is also an analysis for this compound using liquid chromatography:  http://www.nmslabs.com/uploads/PDF/2013_07_08_DBUpdate.pdf

Second, trifluoroacetyl chloride is probably corrosive because it is a highly reactive acyl chloride.  Trifluroacetic acid is a medium strong acid, and may be corrosive for that reason, although I am not certain.  This link has more information:  http://fortox.org/crocodile-designer-drug/

[sociablepsych]

I appreciate the response.  The .pdf you provided does not seem that they are actually analyzing the drug itself but rather just desomorphine or its brand name Permonid.  I believe this is partly because they would not be able to obtain specific homemade samples of Krokodil (being as it reads the analysis is New York state approved) because the drug has not quite made it to the United States.  Perhaps I am reading this wrong though? 

The problem resides in the fact that nothing I have read or seen suggests that any opioid derivative (including desomorphine) would cause skin, tissue, bone and organ deterioration.  Toxicity of this sort suggests another concomitant compound in the homemade solution.  The study I'm referring to I wish I could share but I do not see the ability to unless I upload via some filesharing site.  Either way, they took many different Krokodil samples and urine samples of addicts, alongside the desomorphine (and some other analogues), they found a different compound.  This suggests that even in the un-injected forms of the drug, this compound exists as a product of cooking process.

I suppose again, I am at this point of trying to figure out of if trifluroacetyl bound to desomorphine would contain any corrosive properties. 

[Babcock_Hall]

I found this passage from my second link to be helpful:  "The skin at the site of injection eventually becomes grey and green, scabrous and can flake off and so resembles the skin of a crocodile, hence the name. This is a result of the impurities within the drug (residues of acids and alkalis, petroleum derivatives, industrial oils, organic solvents, red phosphorus, iodine and heavy metals) damaging blood vessels which usually ends up with limb ischemia followed by necrosis requiring surgical intervention and even limb amputation."  I suggest doing a Medline search on this compound, so that you can concentrate on what is in the peer-reviewed literature.

[sociablepsych]

Oh yes, I have done much literature searches regarding the drug.  I have many databases at my disposal in my University's library.  Now, much of what you quoted from that passage is really describes localized damage (i.e., near the injection site) which is understandable.  Someone who injects wrong, poorly, not sanitized is really going to experience many problems locally.  What is puzzling though is the systemic damage that occurs far from the injection site (e.g., rotting of facial bone, ears, nose, lips, etc..).  In essence, without being able to look at the drug myself (even if I could I wouldn't know what to do), I am trying to whittle down particular suspects that would cause systemic rotting.  This could particularly be a futile search, but at least it makes for somewhat of a decent discussion when I write a portion of this paper for my course.

[408]

You will not want to be looking at scientific literature regarding desomorphine to determine why krocodil is so damaging at the injection site.

You want to be seeing how the street chemists make it.  A quick google of "как сделать крокодил"  /"how to make crocodile" leads to a procedure with no importance placed on purification where phosphoric acid, Iodine, and gasoline is definitely in the final product.  Another likely leaves thionyl chloride in the mix.... 

All of these are far worse than a bit of trifluoroacetate in the drug. 

[Babcock_Hall]

"The derivatization of samples was performed as fol- lows: (i) BSTFA (100 μL) was added to the extract evaporated to dryness, and the mixture was kept for 30 min at 55°C to obtain trimethylsilyl derivatives. The sample was evaporated to dryness, and the residue was dissolved in 50 μL of ethyl acetate. (ii) MBTFA or TFAA (100 μL) was added to the extract evaporated to dryness, and the mixture was kept for 1 h at 70°C to obtain trifluoroacetyl derivatives. The sample was evaporated to dryness, and the residue was dissolved in 50 μL of ethyl acetate."

Savchuk, S., S. Barsegyan, I. Barsegyan and G. Kolesov (2008): “Chromatographic study of expert and biological samples containing desomorphine,” J. Anal. Chem. 63: 361-370.

[sociablepsych]

All right, I think I'm understanding this a bit more now that you pointed that out Babcock_hall.  That is indeed also the article I was looking at as well.  So if I understand correctly then, part of the procedure they were using to analyze the substance (compound 1) was MBTFA or TFAA which then creates that trimethylsilyl and trifluoroacetyl derivatives?  Consequently they identify compound 1 as didehyrdodesomorphine (p. 365)?  So then that means, as you stated before, these derivatives are most likely not in the drug itself when it is being cooked.

@408, thank you for more information on the subject, and yes I have been looking through different methods of cooking as well.  There seems to be quite a few variations and I was looking for common ingredients (or impurities) to account for the systemic damage that seems apparent in all of them.

Appreciate all the feedback.  It really helps to talk this over with other people.

[Babcock_Hall]

I can't seem to find a table of abbreviations in the paper, which makes it a little bit more difficult.  BSTFA is an abbreviation for a strong trimethylsilyl donor if I recall correctly.  TFAA is probably trifluoroacetic anhydride.  MBTFA is not an abbreviation with which I am familiar, but I bet someone else here knows what it is.

[sociablepsych]

I looked up those abbreviations as well and found a few, but not all of them.  Those substances seem to be what is causing the trifluoroacetyl & trimethylsily derivatives of desomorphine.  This leaves the compounds mentioned in the beginning (not in the table) as possible perps in causing the caustic nature of the drug.  I suppose also that the gasoline and paint thinner used in other cooking recipes could definitely cause the damage as well.

[Babcock_Hall]

It sounds to me as if there are also infections resulting in gangrene.

[sociablepsych]

Yes, there are problems resulting from gangrene, but those seem to be highly localized at the injection site.  So, systemic damage that has been reported would be things such as: pneumonia, blood poisoning, coronary artery burst, meningitis, rotting gums/tooth loss, bone infection and decayed structure of jaw & face, ulcers/sores on forehead and skull, rotting ears, lips, nose, liver and kidney problems, and some other gangrenous wounds. 

So, what I've been looking for is obviously other chemicals in the drug that could destroy the tissues in such a way that could a)eventually cause gangrene (which is easy if you look at the localized damage) and b)something strong enough to eat away at the facial structure of a person.  Anyway, I think now its just a matter of looking at various chemicals (as I've been doing) and looking at the toxicity of each.  Apparently, after looking at toxicology of red phosphorous, that if it is contaminated with white phosphorous and chronically ingested, it will cause necrosis of the jaw bone.  Then again people are also mixing this with Iodine which could form Hydriotic Acid (HI), so if that gets injected into the system, it would not be great either.  So many substances that are possible considering each batch is different, but they all do have a few things in common.

[Archer]

So, systemic damage that has been reported would be things such as: pneumonia, blood poisoning, coronary artery burst, meningitis, rotting gums/tooth loss, bone infection and decayed structure of jaw & face, ulcers/sores on forehead and skull, rotting ears, lips, nose, liver and kidney problems, and some other gangrenous wounds. 

A large proportion of clandestine desomorphine production is for personal use, i.e. it is conducted by an individual in small quantities rather than by large scale manufacture for distribution to users.

The preparation of desomorphine should not be discussed on this forum in any way but suffice to say that clandestine manufacture is not conducted in a controlled manner, the fumes which are produced by the reaction are extremely destructive to mucous membrances and the soft tissues of the face.

This drug also has a much shorter duration of action compared to other opiates so most of the users short life is spent making the next hit. Nutrition and personal hygeine are not considered to be important so the immune system eventually diminishes.

[sociablepsych]

...the fumes which are produced by the reaction are extremely destructive to mucous membrances and the soft tissues of the face.

And which fumes would these be?  Also, I think it has been well-established that desomorphine in regards to Krokodil is not mass produced by any large scale manufacture...hence why this discussion has been about the effects of the homemade drug which has more impurities in it than if it was made by the "gold-standard" process of creating desomorphine.  Also, the short duration of the drug is also known, this would interact very specifically with neurological pathways such as the mesolimbic dopamine pathway starting at the ventral tegmental area, heading to the nucleus accumbens and to the frontal lobe.  Most drugs interact with dopamine pathway which causes reinforcement and thus addictive behaviors.  The faster acting of the drug, the quicker an addiction can develop.  This is partly why the drug is so dangerous, because those impurities are being introduced quicker and more often than in other drugs.

However, if you could specify what types of fumes that could be produced as a result of many of these different processes, narrowing down health affects as a result would be great for the paper I am writing for this course.  Fumes seems an obvious thing to consider, but if nothing is pinpointed down, even with an educated guess, then it is not much to go on.

[Archer]

I don't want to discuss this on an open forum. Please PM me and I will do my best to point you to the correct literature.

If you could include in your PM the preparative methods which you have encountered as this makes it easier for me to identify the potential fumes which are hazardous to health.