Examples of toxic compounds left in final products for end users.

[Vesp]

As some may know, I am wanting to work even more towards more harm reduction discussion here at The Vespiary. I think an important discussion to help reduce harm on the manufacturing side is to understand what potentially dangerous and toxic by products or side reactions might end up in the final product and hurt a user.
An excellent and famous example of where MPTP was a side product from a Desmethylprodine synthesis which was made and distributed to users and gave them all Parkinson's disease. (http://www.ncbi.nlm.nih.gov/pubmed/18638988)

Perhaps if the manufacturer had better information about such a side product and the dangers of it, he could have avoided the mistake and fewer lives would be ruined because of the war on drugs.

We should discuss what other possible things could come about from all varieties of drugs. Anyone have examples and explanations on how to avoid toxic compounds getting into end products?
If we make such information available, we can all help reduce the harm of drugs and the drug war.

[nintey]

great topic. Hope it gets some interest from folks smarter than me!

[Vesp]

Yeah same here!
I really want to start collecting all the possible issues - even down to things such as "Don't use Phalaris as a DMT source, it has gramine which is toxic... etc"
followed by some recorded incidences, etc.

It seems like the harm reduction movement always focuses on users, but obviously a big part of this is also the manufacturers who obviously have no intentions of hurting their clients. More information on how to make drugs safely is better for everyone.

[embezzler]

A noble endevour - this would have to be written based on synthetic route and by products.

That said I have never seen reliable reports of human toxicity from either safrole or gramine.

[NeilPatrickHarris]

A noble endevour - this would have to be written based on synthetic route and by products.

That said I have never seen reliable reports of human toxicity from either safrole or gramine.

same here, below is some information about safrole's carcinogenic metabolite in rats not being detected in humans:

No evidence exists for sassafras tea or safrole ingestion causing cancer in humans.

In humans, the close amphetamine relative of safrole, MDMA has been shown to protect against cancer formation.[6]

The very closely related allylbenzene myristicin has also shown anti-cancer properties. A 65% inhibition of the tumor multiplicity in the lung was observed as the result of treatment of myristicin in rats.[5]

Animal in vitro tests determined safrole to act as a possibly weak carcinogen, but human tests have not shown this to be the case. Animal tests showing potential carcinogenicity were enough for it to be banned for use in food in the USA, despite no evidence of human carcinogenicity.

The main metabolite of safrole leading to possibly carcinogenicity in rats is 1-hydroxysafrole after SULT metabolism to its sulfate conjugate. However, this metabolite has not been detected in humans after the oral ingestion of safrole using the same tests that found it occurred in rats.[7]

Its believed that the banning of safrole, despite a total lack of evidence of it being carcinogenic in humans, and it's close relatives actually showing anti-cancer effects in vivo, was a move to prevent the sale of safrole because of its use in the manufacture of the illegal drug MDMA.

^ http://herbpedia.wikidot.com/safrole

to go into a little more detail about the claim of the article:

Absorption, metabolism and excretion of safrole in the rat and man.
Benedetti MS, Malnoë A, Broillet AL.

Abstract
The metabolic disposition of different doses of [14C] safrole were studied in rat and man. In both species, small amounts of orally administered safrole were absorbed rapidly and then excreted almost entirely within 24 h in the urine. In the rat, when the dose was raised from 0.6 to 750 mg/kg, a marked decrease in the rate of elimination occurred as only 25% of the dose was excreted in the urine in 24 h. Furthermore, at the high dose level, plasma and tissue concentrations of both unchanged safrole and its metabolites remained elevated for 48 h probably indicating impairment of the degradation/excretion pathways. The main urinary metabolite in both species was 1,2-dihydroxy-4-allylbenzene which was excreted in a conjugated form. Small amounts of eugenol or its isomer 1-methoxy-2-hydroxy-4-allylbenzene were also detected in rat and man. 1'-Hydroxysafrole, a proximate carcinogen of safrole, and 3'-hydroxyisosafrole were detected as conjugates in the urine of the rat. However, in these investigations we were unable to demonstrate the presence of the latter metabolites in man.
PMID: 14422

^ http://www.ncbi.nlm.nih.gov/pubmed/14422

[zekoner]

It seems like the harm reduction movement always focuses on users, but obviously a big part of this is also the manufacturers who obviously have no intentions of hurting their clients. More information on how to make drugs safely is better for everyone.

Firstly i'm glad to find someone interested in manufacture and Harm Reduction as i'm myself heavily involved in Harm Reduction at my little level.
But about manufacturers i'm not sure the majority are all full of good intentions. What to think about Dutch moonrocks who are brown like shit smelling sass and full of byproducts, making users sick; or even if it's a cut about cartels who are cutting cocaïne with levamisole at pasta to Hcl labs level to synergize the effects, and not giving a damn about  health consequences (i will post sources about effects of levamisol on health later if people are interested). BTW if people know a way to remove levamisole simply and i insist on the simply (a little bit like the acetone wash for some of the others cuts) I will be happy to learn it and then share it to users around me.
But yes Harm Reduction Should works towards manufacturers too I totally agreed with you.

[Vesp]

Wow that levamisol thing is really interesting! We should definitely talk about an easy way for people to detect and remove it.
Perhaps a kit exists already to detect it?

[zekoner]

yes i think EZ test a dutch company sell a kit to detect it and i remember seeing somewhere a receipe to make your own i will post it here when i will find it back. Nowdays it is something like 80% of seized cocaine who contains levamisole and sometimes at rates like more than 20% check the energy control website (spanish harm reduction association) they have some analysis of cocaine with up to 22% of levamisole inside if i remember well.
As you seems interrested in the hours coming i will be posting all the informations i get.

edit

so here is the recipe for levamisole test kit http://www.thestranger.com/seattle/levamisole-test-kit-recipe/Content?oid=6854940 BTW in the links there is a very good article about this new trend it's named the mystery of the tainted cocaine.

the why levamisole https://www.ncbi.nlm.nih.gov/pubmed/24440755

too speak effects of levamisole the most common secondary effect is agranulocytosis. To have much info on levamisole secondary effect hit Pubmed.

https://www.ncbi.nlm.nih.gov/pubmed/?term=levamisole+cocaine

[Impossible]

Levamisole base is far more solublein hexane than the cocaine freebase.

Multiple water/hexane washes of freebase, discarding hexane layers, is shown to effectively separate the two compounds.

Ref: http://www.justice.gov/dea/pr/microgram-journals/2013/mj10-1_12-16.pdf

[myhero]

discarding hexane? From reading it seems that Cocaine base is soluble in hexane and it's the water we need to discard.

For mixtures of cocaine base/tetramisole base, the best method to purify the cocaine was a liquid/liquid separation employing hexane and water; five water washes suc- cessfully removed tetramisole base from the cocaine.

[Baba_McKensey]

page 504 contamination with o-toluidine
http://books.google.com/books?id=OWFiVaDZnkQC&pg=PA505&lpg=PA505&dq=toluidine+anthranilic+polyphosphoric&source=bl&ots=58uM1eubxO&sig=uNFEEs4fiyUFKqswAZ03E9SVncg&hl=en&sa=X&ei=G5IZVLWvGuHJ8AG6s4HgDQ&ved=0CCUQ6AEwAw#v=onepage&q=toluidine%20anthranilic%20polyphosphoric&f=false

[Scarecrow]

The Hofmann rearrangement on helionamide forms 2-Cl-4,5-MDA as a side reaction (http://dx.doi.org/10.1016/j.forsciint.2012.10.002), this byproduct forms in particularly large amounts when a large excess of chlorine is used. Cyanuric acid also forms if TCCA is employed as a chlorine source. Removal of cyanuric acid should be done by vacuum filtering the cold reaction mixture before heating and discarding the precipitate. If not, taking your crude MDA it should be basified then steam distilled, extracted into something more selective such as ether, left to evaporate then MDA freebase should be vacuum distilled.

[Vesp]

Whay does 2-Cl-4,5-MDA so on a neurological basis?

[Scarecrow]

I dont know much about this compound, apparently MDA contaminated with the chloro derivative gives the MDA experience far more negative/bodyload effects but I dont know this from my personal experience. Ive attached the full article if you want to have a more detailed look.

[thewire]

There isn't much  in the literature about  x-MDAs.

2-BR-4,5-MDA
http://www.erowid.org/library/books_online/pihkal/pihkal019.shtml

It is just an unwanted compound. Everybody wants a 100%  pure product or at least as pure as possible.

[Burgi-Dunit-Again]

Toxicity data on the chloro-mda compound would be great, but I don't think much is available as yet sadly

People are also using a crude mixture of aldehydes/ketones (stemming from oxidation of a conspicuously ecstasy-like aldehyde) in reductive amination to yield MDMA as well as "n-methyl piperonylamine" and "n-methyl-helionamine." A quick search for the former didn't bring up any leads, but I'm sure some sort of toxicology study for this compound exists. It is well established as a byproduct of MDMA synthesis from a variety of routes.. For the n-methyl helionamine there is unlikely to be any data available.


As to something I actually can weigh in on: when synthesizing DMT from tryptamine by reductive methylation with formaldehyde, if special precautions are not taken one will form a substantial amount of pictet-spengler cyclization product 2-methyl tetrahydrobetacarboline. Given the structural similarity between this compound and MPTP, its ability to selectively destroy dopaminergic neurons in the substantia nigra is of utmost concern.

Interestingly, the compound has been isolated from brain and nerve tissue, so it is produced endogenously to some degree.

As with MPTP -> MPP+, the 2-me-thbc needs to be first oxidized in vivo to form the potentially toxic species. While the beta carboline is a poor substrate for MAO (this is good), it CAN be oxidized to the "toxic" compound by heme peroxidases. See Herraiz, Tomás, Hugo Guillén, and Juan Galisteo. "N-Methyltetrahydro-?-carboline analogs of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxin are oxidized to neurotoxic ?-carbolinium cations by heme peroxidases." Biochemical and biophysical research communications 356.1 (2007): 118-123.

Studies using direct intracerebral perfusion of the 2-me-thbc into rat brains suggest that it does NOT destroy dopaminergic neurons in the manner that MPTP or MPP+ does, however perfusion of the pre-oxidized beta-carboline (2-mbc+) is neurotoxic, though to a lesser degree than MPP+. The thought is that the beta-carboline is not efficiently oxidized by MAO, and so toxic levels of 2-mbc+ are never reached (phew). See: Rollema, Hans, Raymond G. Booth, and Neal Castagnoli. "In vivo dopaminergic neurotoxicity of the 2-?-methylcarbolinium ion, a potential endogenous MPP+ analog." European journal of pharmacology 153.1 (1988): 131-134.

More good news: when monkeys were loaded up with 2-me-thbc on a daily basis, they did not get parkinson's disease! Collins, Michael A., and Edward J. Neafsey. "?-carboline analogues of N-methyl-4-phenyl-1, 2, 5, 6-tetrahydropyridine (MPTP): Endogenous factors underlying idiopathic Parkinsonism?." Neuroscience letters 55.2 (1985): 179-184.

So the moral of the story? The impurity from sloppy DMT synthesis will probably not give you parkinson's disease. But it's still a good idea to keep the temperature low in your methylation and avoid taking any risks


Now some bad news for methcathinone fans: Trace amounts of permanganate left in the product after oxidation of [pseudo]ephedrine will cause irreversible damage to the basal ganglia, resulting in permanent parkinsons-like symptoms including changes in gait and speech. See Stepens, Ain?rs, et al. "A Parkinsonian syndrome in methcathinone users and the role of manganese." New England Journal of Medicine 358.10 (2008): 1009-1017.

It should be noted that the participants in the study were heavy intravenous users.. But even still, Beeee safe folks. No buzz is worth permanent neurological damage.

[lullu]

There are a variety of forensic journal paper showing a vast number of byproducts by lots of common routes used by users on this board, it seems to me a lot of people here
would profit from better literature reviews, you have a responsibility if you are going to market or share your product.

At least running TLC's should be the norm here for all of us!

Talking of which, did you notice byproducts after recrystallization of the DMT Burgi? I guess correct recrystallization and running the reaction can yield a very clean product (see miamiechin, he ran a HPLC on hyperlabs) and I think another person had fairly good mp on his product too, but yes this concerned me too in the past.

Talking of DMT, here is another good example (see attachment) of what you would not suspect.
For all people who love DCM for whatever reason have a look at this

Harm reduction should not only mean to be concerned about purity but also about health of the chemist and pollution. I've yet to see a thread talking about waste reduction / disposal or health concerns regarding solvents used in workup.

[Burgi-Dunit-Again]

I was able to get GC-MS data on a well-recrystallized sample that showed no beta-carboline presence. Before crystallization it was below 1%, but still disconcerting, as the methylation was performed with very careful technique.

A sample containing nearly 40% beta-carboline could not be cleaned by crystallization or even distillation. The two compounds have very similar solubility properties and boiling/melting points..

As long as you recrystallize and mind the temperature you should be fine. Endogenous compounds concern me much less than some of these chlorinated amphetamines.. or even the trace amounts of bizarre beta-carbolines formed during the decarboxylation of tryptophan.

[thewire]

6 Chloro MDMA
http://www.bluelight.org/vb/archive/index.php/t-390422.html

6-hydroxydopamine
https://en.wikipedia.org/wiki/Oxidopamine

Pathways of MDMA metabolism
http://pharmrev.aspetjournals.org/content/55/3/463/F3.expansion.html

Quite likely  that the x-derivatives of both MDA and MDMA are  neurotoxic.

The Identification of 2-Chloro-4,5-
methylenedioxymethylamphetamine in an Illicit
Drug Seizure

http://bitnest.ca/Rhodium/pdf/forensic/6-chloro-mdma.pdf

[YaYa]

Traces of heavy metal in vitamins = traces of heavy metal in drugs
Drugs full of impurities = retarded cash hungry chemists as cleaning many products is the easy part, if not easiest part of most drug synthesis from what I understand
Being chemist and not lab testing your product (especially some novelty shit) in a proper lab analysis before letting it go on market = pissing in food to costumers in your restaurant, and making sure piss is not sterile at all