Beta Carboline MAOIs - towards a more effective e-liquid

[deusXmchna]

Somehow I got the word "fractional" or something in my head, sorry. This one looks good as a whole kit of stand/holder/funnel for a little over $50.

Since I started the sep funnel mess..
Apparently that's a crappy ringstand. Reading up on the 1l sep funnel & stand from the same vendor, the review said it was a light plastic base. That plastic "sep funnel holder" looks pretty sketchy too. Maybe I'm old and crotchety, but a ringstand should use a (metal) ring, not a plastic semi-circle. Clamps... clamps... you can never have too many extra clamps.
My equip has been mothballed for well over a decade and I don't remember exactly what it's made of, but the base on my ringstand is HEAVY. So, either that one is sub-par, or they-don't-make-um-like-they-used-to.
Don't ever skimp on equipment. You want heavy, thick, solid, sturdy. (just like I want my women.)

I found this. Cheap, glass, and probably to the task (of the final separation- not the entire a/b):
glass baster

 

[kinabaloo]

aprioristic -

simple truth is we don't don't for sure which alkaloids are important/useful, but we do know that the full range does the trick. Working out which we really need is something for the future, perhaps (or perhaps never).

I wouldn't put too much weight on CigRx including Anatabine; their website claims that nicotine is the addictive compound!

It might (or might not) be more to do with the harmala alkaloids (though in very small amounts).

It might well be a hundred years hence before we can better the tobacco alkaloid mix.

 

[DVap]

Tuesday will write up the method in a new thread. Hopefully it will be sufficiently tested and verified by then. I will do another run-through myself before then also.

So any experiences and coments, speak up !

It would be nice to have a figure for the overall extraction efficiency; looking like it will be over 90%.

And that the calcium carbonate / hydroxide removal of excess citric acid is effective.

I think there are a few trials in the pipeline so after the weekend, we should hopefully be able to tie some things down, else we'll estimate.

Don't want to lose the momentum.

Good idea going after verification that the acid neutralization works. If I had a nickel for all the things I've seen that worked on paper, and not in the lab, or only after considerable tweaking, I'd be swimming in nickels.

Getting a figure for extraction efficiency isn't easy. There is a single test where I was able to get a recovery comparable to a lab WTA procedure, but that procedure itself has an unknown recovery, so while there is evidence to quote 90%+ relative to another procedure, there is no evidence to quote 90%+ recovery relative to the actual content.

We could say "90%+ assuming a 1.2% alkaloid content", and that would be sufficiently qualified.

Better to make a more conservative statement that's been verified/tested than a more ambitious statement that hasn't!

 

[kinabaloo]

We could say "90%+ assuming a 1.2% alkaloid content", and that would be sufficiently qualified.

Better to make a more conservative statement that's been verified/tested than a more ambitious statement that hasn't!

Good point !

 

[DVap]

You are talking about Normality here right? I actually didn't catch how much sodium carbonate people are using per 20ml solution or whatever, but I am going to make an effort to go through this thread again later today. Let me see if I understand the basic idea though:

The further above the target alkaloid's pKa, say nicotine at roughly 8, which the alkaline solution is, the greater amount of freebase salts will be extracted from the tobacco. So, if we're using acids/bases that aren't strong enough, we might not get an accurate ratio of what naturally occurs in tobacco.

Each tobacco alkaloid is going to have it's own degree of protonation (single -vs- non & single -vs- double) -vs- pH graph. For practical purposes, I've only seen the graph for nicotine, and I've identified the ~95%+ double protonated and ~95%+ non protonated pH's as occurring at pH=2 and pH=9. One could try to come up with greater granularity than this for individual alkaloids, but I wouldn't be that person! Far too much work -vs- the near certainty that pH < 2 or pH > 10 would be sufficient to take care of the whole affair.

By "required" here, I take it that you mean that a fairly concentrated sodium carbonate solution, or relatively weak solution of something higher pH is good enough for a "kitchen method" to get what kinabaloo called 90% WTA.

Whatever it takes for the pH to be > 9 and perhaps more desirably > 10 (I don't like "working on the edge").

After finding this PDF, it seems clear that the alkaloid profile varies between types of tobaccos (see Tables 2/3). So that makes me want to go back to the neurochemistry of these alkaloids individually and ask what exactly it is that we want.

Also, I assume that I will end up with nornicotine (7.75 pKa) no matter what, but I don't think we want 4-(N-methyl-N-Nitrosoamino)-Nornicotine (9.46 pKa) or 2,2'-Bipyridine (Dipyridyl, 4.55 pKa).

Maybe I am just confused here, but besides Anabasine @9.2, there is nothing else that high of pKa, so maybe we don't even want to use a very strong basic solution? I'm having a hard time though finding out what these things like anabatine and anabasine really do to us though.

Generally speaking, these are good and interesting questions/points, but on the more practical side, this sort of procedure just doesn't have the degree of selectivity required to selectively recover or leave something behind. There are miscellaneous chemical tricks that might operate on one alkaloid -vs- another, but I wouldn't support or encourage such tweaking.

Looking at CigRx again, it is anabatine and yerba mate extract. I found some stuff about Native Americans and tobacco which said that the species containing more anabatine/anabasine and little nicotine were used similarly to the more popularly cultivated nicotine-containing species. We have plenty of pure nicotine and I take it that we don't get much mg/ml out of these extractions anyhow, so why shouldn't we be extracting from a species like n. glauca if we are after stuff like anabatine?

Different plants certainly have different profiles, and as you mentioned nicotiana glauca (aka tree-tobacco), it's a great example of a plant with an extremely slanted (toward anabasine) alkaloid profile. My instinct is to stay with regular old nicotiana tabacum since it is what we're accustomed to and it tends to kill us, um... more slowly , so it offers, perhaps, the minimum of surprises in not getting a LOT of something we're used to getting a little of.

Somehow I got the word "fractional" or something in my head, sorry. This one looks good as a whole kit of stand/holder/funnel for a little over $50. I only got to talk to my brother briefly last night, but it looks like we might do two batches, one along the lines of the kitchen process here that should be relatively safe for the untrained, then he seems to know what to do in some sort of lab procedure. It seems like he can use his lab, but probably not any of their chems. I got the idea that some of the hardware-store type solvents really aren't good to use, or need removed by vacuum. He seems to have various ideas about making the WTA more pure, so I am just going to leave that up to him.

As for the hardware store solvents, to say they "really aren't good to use" is an understatement. The grade on this stuff is generally "technical", which means "mostly", which also means "some" of God only knows what (well, God and we mass spectroscopists). Some kitchen chemists don't scare me that much.. but the one who would go to the hardware store for solvent, that guy scares the hell out of me and makes we wonder if I want to be within 100 miles of this thread. Without belaboring the point, because I've made it before at length, don't be that guy!

 

[kinabaloo]

Thanks again for your efforts kina. This really is your baby.

But actually it is not - tceight is the real developer; I can perhaps lay claim only to the (as yet untested) removal of the excess citric acid - quite a big thing if it works

So maybe it would be better for tceight to write it up (and welcome to borrow any text, pics etc).

 

[DVap]

I recently did a test of alkaloid partitioning in water -vs- organic at various pH values using the WTA made from the Thunder Snus that KathyD26 sent me (her impressions here). I was a little grumpy because I had to take my purified and isolated alkaloids and put them in water/organic and start hitting it with acids and bases to get the various pH values to eyeball where (which phase) the tinted alkaloids ended up and it would be a lot more work to re-isolate them. But since several hundred mg of alkaloids is nothing to waste, I went through the steps to isolate these alkaloids this evening, and decided to see what might happen if I went to extremes and did a couple more exchanges of the already essentially pure alkaloids.

The first observation I could make after reducing to pure alkaloids is that each acid/base exchange pair takes a bit of a toll on the alkaloid yield. I know what I started with, and I know what I got back in the end. The extra cleanup steps appeared to take about a 10% share each, so I lost a good 20%. Worth it? Probably not due to the fact that these alkaloids were already essentially pure from the extraction/cleanup previously done. However, the extra steps did take a bit off the tint, not much, but a little. Here's 20 mg/mL of extra-purified akaloids in VG/PG -vs- deionized water.



That's some mighty tasty alkaloids.

This suggests that the cleanup steps I've done to go from a more technical alkaloid grade (alkaloids plus a good bit of tobacco matrix) to a purified grade probably reduce my yield a good 20%. Which would further suggest that if I'm consistently getting about 12 mg alkaloid per gram of tobacco, I'm probably extracting a bit more, perhaps 15 mg/g and losing some of them for the sake of purity, which further suggests that American Spirit tobacco is probably at least 1.5% alkaloids. If I had to take a good hard guess, I'd say that the available alkaloids (if a 100% extraction efficiency could be achieved, it really can't.. at least not without heroic effort) would be closer to 1.8 - 2%... which would be very much in line with American Spirits' reputation as a good strong tobacco. (There's nothing authoritative about this guess, so don't quote it as gospel...it's just my chemists' gut feeling). If 2% were the working guess, this would mean I'm getting 60% in the end, from about a 75% extraction.

I also need to eventually reconcile the color of the alkaloid isolate obtained from a sodium carbonate/mineral oil extraction -vs- my normal procedure. The isolate from the sodium carbonate/mineral oil extraction was noticeably less tinted than that which I consistently get with my lab procedure. Since the pH is pretty tightly controlled, I have to wonder if it's not something about the mineral oil. I can't speculate too far on why the color is different (That's why we have Kin!), but it's worth running to ground. Perhaps the oil extraction doesn't pull alkaloids from the tobacco quite as aggressively as my procedure? This would suggest a somewhat modified alkaloid profile in the oil extraction product -vs- my lab extraction. If this were the case, what would it mean for the efficacy of the alkaloids from an oil extraction? I would hope not very much, but again, it just something that I think I need to look at some more. The proof is, as they say, in the pudding, and if an oil extraction is doing x-factor duty acceptably, then it's got what it needs to have.

Lol.. so many tests, so little desire to do them all!

Anyone else tired of listening to me talk, or am I the only one?

 

[kinabaloo]

Might be that mineral oil is not a good solvent. Not that it needsto accept much, but compared to veg oil, much paler color. Mineral oil: pale yellow; veg oil: deep amber.

In 1ml of oil we expect to hold ~50 mg+. That is 50g / liter - not a lot. But maybe it simply is a poor solvent.

Might be worth looking again at veg oils. I'm not too worried that there might be some free glycerine (joins water layer, no harm) and vitamin e (stays in oil layer, no harm). It shouldn't make much difference to the end product. And soap is not produced without considerable heat.

Alternative I guess is more oil; and slow transfer to acidified water because that will be in far lower volume.

 

[DVap]

The oil seems to be a good enough solvent to extract from the solid matrix, but is perhaps not quite as aggressive. The color of the oil really won't make any difference. That's long gone with purification. Again, interesting, worth looking at again, but perhaps nothing to get hung on.

 

[kinabaloo]

The oil seems to be a good enough solvent to extract from the solid matrix, but is perhaps not quite as aggressive. The color of the oil really won't make any difference. That's long gone with purification. Again, interesting, worth looking at again, but perhaps nothing to get hung on.

But you just said the color is different with mineral oil than for lab solvent. So maybe it is just more dilute?

 

[kardenm]

But actually it is not - tceight is the real developer; I can perhaps lay claim only to the (as yet untested) removal of the excess citric acid - quite a big thing if it works

So maybe it would be better for tceight to write it up (and welcome to borrow any text, pics etc).

Yes. tceight and Dvap. But that's not what i mean. You put it all together and coordinated the information. Without that organizing we wouldn't have a simple, summarized method. Lots of people can and have done various and similar extractions (for many years). Heck, I myself did lots of extracting of alkaloids from other plant material back in my hippie days (ever here of the Isomerizer!?). But, lots of geeking chemist would not take the time to do anything other than just report some results or details of their lab methods. Keeping track of what everyone is doing and reporting and turning that into useful information, well, that's your baby.

 

[kinabaloo]

DVap - it's a bit confusing ... you analysed KathyD'd watr extraction (Virk style) ??

And I guess separately you are saying that even purified alkaloids diminish by 10% at each acid/alkali transiton? Why would that be ?!

 

[DVap]

But you just said the color is different with mineral oil than for lab solvent. So maybe it is just more dilute?

I'm referring to the color of the concentrated alkaloids after they've been purified leaving essentially zero non-alkaloidal material.

 

[DVap]

But, lots of geeking chemist would not take the time to do anything other than just report some results or details of their lab methods.

Pardon me if I take your comment as a shot, but that's rather how it sounds. I'm hoping it's just me being overly sensitive and reading into it something that's not there... because if it was intentioned, you need to read up a few thousand posts of background first and spout off later.

Those geeking chemists sometimes also spend a great deal of their time, money, and effort experimenting, recruiting testers, and trying to make damned sure nobody gets harmed in a proof of concept based around a lab method to get an idea off the ground that might have otherwise come to nothing, gotten lost in theoretical non-action, or taken a great deal longer to come to light, if at all.

If I read your tone all wrong, my apologies in advance.

 

[DVap]

DVap - it's a bit confusing ... you analysed KathyD'd watr extraction (Virk style) ??

And I guess separately you are saying that even purified alkaloids diminish by 10% at each acid/alkali transiton? Why would that be ?!

The snus that Kathy sent was extracted and cleaned up to pure alkaloids. I took the half of the product that I didn't send to her and did the pH based partitioning tests with it.

Partition coefficients better than around 5:1 are usually effective for getting a good enough separation with some loss inherent. In the case of the alkaloids, I'm starting to more suspect that we're looking at an organic -vs- aqueous partition coefficient of perhaps 8 or 10 to 1, even with pH carefully controlled which means the more twiddling around, the more the loss. And while we hope for large partition coefficients of 100:1 or such, in real life, we don't always get them... c'est la vie.

The entirety of this whole pursuit is much more complicated than folks might imagine... each detail, in fact, has sub-details, and so on. The reality here is (and tceight would agree, I suspect) that this whole kitchen procedure is fundamentally a case of "doing it all wrong" (by design to avoid more correct and far more hazardous procedures) and still coming to a workable outcome... a bit brute-force, but with a certain elegance all the same.

 

[kinabaloo]

The snus that Kathy sent was extracted and cleaned up to pure alkaloids. I took the half of the product that I didn't send to her and did the pH based partitioning tests with it.

Partition coefficients better than around 5:1 are usually effective for getting a good enough separation with some loss inherent. In the case of the alkaloids, I'm starting to more suspect that we're looking at an organic -vs- aqueous partition coefficient of perhaps 8 or 10 to 1, even with pH carefully controlled which means the more twiddling around, the more the loss. And while we hope for large partition coefficients of 100:1 or such, in real life, we don't always get them... c'est la vie.

The entirety of this whole pursuit is much more complicated than folks might imagine... each detail, in fact, has sub-details, and so on. The reality here is (and tceight would agree, I suspect) that this whole kitchen procedure is fundamentally a case of "doing it all wrong" (by design to avoid more correct and far more hazardous procedures) and still coming to a workable outcome... a bit brute-force, but with a certain elegance all the same.

I see.

Had to reboot just now

 

[kinabaloo]

Strange if the freebase alkaloids 'dissolve' better in water than in mineral oil! Are they just in suspension in e-liquid and lab WTA ?

Hydrogen bonding?

Maybe it's not so much that the mineral oil is a poor solvent, but that the freebase alkaloids are not unhappy in water (are slightly polar).

Maybe use acetone or ethanol instead of water, then the freebase alkaloids will more readily migrate to the oil ?

If do use water, maybe makes sense to ensure that it is fully saturated with carbonate (with extra carbonate powder); leave no roon for the alkaloids.

 

[kinabaloo]

I'm referring to the color of the concentrated alkaloids after they've been purified leaving essentially zero non-alkaloidal material.

Hmmm ... will have to give this some thought; but seems either the spread of alkaloids is different, or their oxidarive state (for some reason).

ps: don't think kardemon meant anything other than comment on my role, and wasn't thinking of you; just an oversight if you will; sometimes words alone read different to the thought.

 

[DVap]

Strange if the freebase alkaloids 'dissolve' better in water than in mineral oil! Are they just in suspension in e-liquid and lab WTA ?

Hydrogen bonding?

Maybe it's not so much that the mineral oil is a poor solvent, but that the freebase alkaloids are not unhappy in water (are slightly polar).



Maybe use acetone or ethanol instead of water, then the freebase alkaloids will more readily migrate to the oil ?

If do use water, maybe makes sense to ensure that it is fully saturated with carbonate (with extra carbonate powder); leave no roon for the alkaloids.

Not suggesting that at the free alkaloids would dissolve better in water at all. The idea of saturation with one component to leave no room for another quite different component isn't really one that I've ever come across. Not to say there can't be cases where this might apply, but I'd guess they'd be so specific as to not leave any room for generalization.

A partition coefficient, is simply, the ratio of how much of a material ends up in one specific phase -vs- another specific phase. One commonly quoted pair is octanol and water. Say we have a gram of a particular compound, and when shaken in a vial containing solvent A and solvent B, 800 mg ends up in solvent A and 200 mg ends up in solvent B. We would say that the solvent A/solvent B partition coefficient is 4 (800 mg/200mg). 4 isn't very ideal at all.

The mistake that might be tempting to make here is to assume that we can easily find solvent pairs that display large partition coefficients for the compound(s) of interest such that we can get 100% into one of the phases. Doesn't happen as often as we'd like (and not always with the most convenient/economical/available solvent pairs), or rather, whole methodologies are created around such an ideal situation. Ultimately, when there is a less than "perfect" partitioning, we have to be more aware of the trade-off, especially when performing repeated cycles.

A long while back, I came across and posted a link to an article that was excellent. It warned against getting too caught up in a "specific principle" when looking a complex system... there are a lot of principles at work, and we can fail to fully appreciate and account for their interactions or even their presence in the first place.

 

[DVap]

ps: don't think kardemon meant anything other than comment on my role, and wasn't thinking of you; just an oversight if you will; sometimes words alone read different to the thought.

Dunno, if one was taking a shot at my general "coyness" about not getting into any detail about my procedures, better words couldn't have been chosen. The comment, "But, lots of geeking chemist would not take the time to do anything other than just report some results or details of their lab methods." seemed just a bit directed as I'm about the only person here who resembles that comment.

It probably was inadvertent, but I'm a bit on edge since I've got a nervousness about this process that I've been pretty open about. I could be much more helpful than I am here, but it would read like gibberish to most, and lead others down alleyways they'd probably best not go down. Part of me cringes at the details of the procedure, but I also understand what tceight set out to do. In that we have the context of my comment earlier about, "doing it wrong and getting a workable result". I've discussed much of this in some detail with tceight, and there are a lot of things he'd do differently with the procedure if he really wanted to optimize it, but then he'd be forgetting his over-riding goal... to steer clear of the more hazardous procedures that this would require.

pH and partitioning are the 800 pound gorillas in this whole affair. The initial extraction is as much a physical process as a chemical one.... getting desired compounds to leave the matrix so we can chuck the matrix. After that, it's all acid/base manipulation, far less physical and far more chemical.