Any interest in determining nicotine--by DVAP

[DVap]

Anyone ever wonder why ethylene glycol is considered toxic while propylene glycol is not?

It's all about what happens when the body oxidizes the two molecules.

Ethylene glycol is metabolized (oxidized) to oxalic acid (the simplest dicarboxylic acid). Oxalic acid has an affinity for metal cations, which messes up blood chemisty, and ultimately tends to form insoluble precipitates which gather in the kidneys. In short, the body doesn't know what to do with it, so it does what it can with it, none of which are good.

Propylene glycol, on the other hand, is metabolized (oxidized) to pyruvic acid. The body knows what to do with this stuff. The pyruvate dehydrogenase enzyme goes to work on it, and pretty soon the citric acid cycle takes over, and it's metabolized for energy.

Relax, there will not be a test.

[exogenesis]

Very nice work DVap, good to see some informative & practical chemistry analysis here.

But one thing comes to mind, if this is a simple base titration with acid,
then it's measuring only the free-base nicotine proportion of that present.
Wouldn't some of it already be in the salt form, for whatever reason ?
(e.g. from reactions with additives, or even from direct formulation pH-modification).

This is an older post showing the (theoretical / possible) ratio of nicotine free-base/salt with pH
(supposedly this is for smoke, no specific liquid 'matrix', so it's a bit generic).

pH and nicotine

If e-juice intially at pH 8.3 did 'only' contain 60% freebase, then wouldn't the titration
method read 40% low ?

Not knocking you efforts, which are great,
just curious to know


PS, if refrigeration for long term stability was important,
I'd use PEG-400, since it solidifies at ordinary fridge temps (4 ish deg.C),
I'm using a juice with this & it's definately stopped the progressive
'pinking' and 'browning' seen with PG & VG,
although the latter also change much slower when cooled.

[kinabaloo]

The other day, I checked out Chris Yeltin's website myfreedomsmoke.com

He's got e-liquids for sale at volumes large and small, and the price seemed pretty good, so I bought 60 mL of 48 mg unflavored. It ran me $36.95 plus $5.95 for USPS Priority shipping, so I paid $42.90 for 60 mL of the 48 mg e-liquid.

I don't know the guy, never talked to him, just bought from him this once.

You might be wondering how the 48 mg unflavored liquid from myfreedomsmoke.com tested.

Replicate 1: 45.5 mg
Replicate 2: 46.1 mg
Average (replicate 1 & 2): 45.8 mg
Average % of labeled concentration determined: 95.4%

This is an excellent result. I'll be buying from Chris again.

(If I'm off 5% either way, it could range from 43.5 - 48.1 mg).

This stuff is legit.

This is important because it shows (in all likelihood though not sufficiently robustly statistically speaking) that your measuring is accurate - and accurate in this range.

The 4% could be explained by oxidation?

Any thoughts on whether oxidised nicotyine could still be psycho-active / become so when heated, or is it permanently lost, usefully speaking, when this occurs in an e-juice?

I'd love to join in with this practically but am seriously short of time (and my science background leans more to physics than chemistry, though i understand titration, no problem).

Even with just the one person out here who might test anything at anytime, it can only be doing us all a big favor (and the companies themselves too, in fact).

[Mister]

DVap, thank you so much for your work and your sharing of knowledge about this subject!

If you have the time and an interest in it, there's another subject which I'd love to hear your thoughts about.

It seems that the body metabolizes one stereoisomer of propylene glycol far better than the other. It also seems that all commonly available propylene glycol is racemic, presumably including all that we vape. Do you know of any way to isolate the stereoisomer our bodies are better equipped to deal with? That might make significantly better eliquid. Perhaps an eliquid without negative affects for any user.

There's a thread on this subject if it interests you: Enantopure Propylene Glycol ?

BTW, I'm a layman, please forgive my (probable) misuse of terminology in some of my posts about this.

[kinabaloo]

Anyone ever wonder why ethylene glycol is considered toxic while propylene glycol is not?

It's all about what happens when the body oxidizes the two molecules.

Ethylene glycol is metabolized (oxidized) to oxalic acid (the simplest dicarboxylic acid). Oxalic acid has an affinity for metal cations, which messes up blood chemisty, and ultimately tends to form insoluble precipitates which gather in the kidneys. In short, the body doesn't know what to do with it, so it does what it can with it, none of which are good.

Propylene glycol, on the other hand, is metabolized (oxidized) to pyruvic acid. The body knows what to do with this stuff. The pyruvate dehydrogenase enzyme goes to work on it, and pretty soon the citric acid cycle takes over, and it's metabolized for energy.

Relax, there will not be a test.

I could pass this one

Excellent simple yet thorough explanation.

[kinabaloo]

Very nice work DVap, good to see some informative & practical chemistry analysis here.

But one thing comes to mind, if this is a simple base titration with acid,
then it's measuring only the free-base nicotine proportion of that present.
Wouldn't some of it already be in the salt form, for whatever reason ?
(e.g. from reactions with additives, or even from direct formulation pH-modification).

This is an older post showing the (theoretical / possible) ratio of nicotine free-base/salt with pH
(supposedly this is for smoke, no specific liquid 'matrix', so it's a bit generic).

If e-juice intially at pH 8.3 did 'only' contain 60% freebase, then wouldn't the titration
method read 40% low ?

Not knocking you efforts, which are great,
just curious to know


PS, if refrigeration for long term stability was important,
I'd use PEG-400, since it solidifies at ordinary fridge temps (4 ish deg.C),
I'm using a juice with this & it's definately stopped the progressive
'pinking' and 'browning' seen with PG & VG,
although the latter also change much slower when cooled.

Exo - i did wonder that too but it would seem from the results that come out right that this possibility doesn't affect the practical results. Be interested to hear from DVap on this - and on freebase generally.

Good to see some confirmation re refrigerating for long-term storage too.

edit: Went back to review the pH-freebase% data; and the change is more dramatic than i had remembered.


http://www.exogenesis.co.uk/FreebaseNicotineWithpH.jpg

[kinabaloo]

DVap, thank you so much for your work and your sharing of knowledge about this subject!

If you have the time and an interest in it, there's another subject which I'd love to hear your thoughts about.

It seems that the body metabolizes one stereoisomer of propylene glycol far better than the other. It also seems that all commonly available propylene glycol is racemic, presumably including all that we vape. Do you know of any way to isolate the stereoisomer our bodies are better equipped to deal with? That might make significantly better eliquid. Perhaps an eliquid without negative affects for any user.

There's a thread on this subject if it interests you: Enantopure Propylene Glycol ?

BTW, I'm a layman, please forgive my (probable) misuse of terminology in some of my posts about this.

Very interesting, even if of no practical signifance (no viable source of natural PG and no way to separate the isomers). The body's better handling of one isomer suggests natural selection for the one found in natural foods (yet some random and not always good, yet not disastrous, things get coded into dna too sometimes; like our inability to make ascorbic acid). Juice PG is derived from the petrochemical 'natural gas' so would have both isomers, afaik.

Hope to get some time to look into this later, starting with your link.

[DVap]

I think I covered the state of the nictotine freebase vs salt in a previous post. The comment I made was that the presence of other bases would bias the nicotine result high while the presence of acidic components would present a low bias. I selected bromothymol blue as the indicator because it goes yellow at pH 6, and once all base is consumed, the drop past pH 6 with 0.1N acid is rapid. While it's possible to have other tobacco alkaloids determine as nicotine, I can't see why anybody would be acidifying the e-liquid they sell.

I would not assume oxidation as the reason for a 95+% result on the liquid I analyzed yesterday, it can more likely be put down to a) experimental error, or b) that's the real concentration in the liquid.

As for the stereochemistry of propylene glycol, it's the asymmetrical carbon that gives rise to enantiomerism. You'd need an optically pure starting material to synthesize an optically pure single enantiomer of PG.

Metabolically, on it's path from PG to pyruvic acid, I see nothing that would stand in the way of oxidation of either component of the racemic mix to pyruvic acid. Here's the rub, pyruvic acid is not chiral. So I wonder if the body ultimately cares?

[kinabaloo]

I think I covered the state of the nictotine freebase vs salt in a previous post. The comment I made was that the presence of other bases would bias the nicotine result high while the presence of acidic components would present a low bias. I selected bromothymol blue as the indicator because it goes yellow at pH 6, and once all base is consumed, the drop past pH 6 with 0.1N acid is rapid. While it's possible to have other tobacco alkaloids determine as nicotine, I can't see why anybody would be acidifying the e-liquid they sell.

I would not assume oxidation as the reason for a 95+% result on the liquid I analyzed yesterday, it can more likely be put down to a) experimental error, or b) that's the real concentration in the liquid.

As for the stereochemistry of propylene glycol, it's the asymmetrical carbon that gives rise to enantiomerism. You'd need an optically pure starting material to synthesize an optically pure single enantiomer of PG.

Metabolically, on it's path from PG to pyruvic acid, I see nothing that would stand in the way of oxidation of either component of the racemic mix to pyruvic acid. Here's the rub, pyruvic acid is not chiral. So I wonder if the body ultimately cares?

I believe that some recipes do add citric acid (not sure why as it would not vaporise; preservative perhaps); not enough to alter the pH too much though one would imagine. Would be nice to know the pH of the anomolous juice though.

RE oxidised nic - should be very little in anopened juice; i guess that your point. Once oxidised could it still be active/activated?

[DVap]

I believe that some recipes do add citric acid (not sure why as it would not vaporise; preservative perhaps); not enough to alter the pH too much though one would imagine. Would be nice to know the pH of the anomolous juice though.

RE oxidised nic - should be very little in anopened juice; i guess that your point. Once oxidised could it still be active/activated?

I'm not convinced that a solution equi-molar in citric acid and nicotine (both weak) would neutralize in the same manner a strong acid will neutralize nicotine.

If there were citric acid, the question would be how much? My next question would be why?

Citric acid decomposes at 175°C into water and aconitic acid (the body can handle it) which itself decomposes around 200°C with acrid smoke. The temperature at the business end of an atomizer (especially one on the dry side) would likely easily reach 175°C (347°F). In short, citric acid, at a glance, isn't something I'd want in my e-liquid.

Back to the possibility that formulation can mask nicotine in a titration. I've already conceded that as a possible stumbling block. I can envision a simple cleanup using extraction of e-liquid from basic solution, evaporation of the solvent, and addition of water to a known volume to eliminate any possibility of bias from acidic species in the e-liquid matrix. The recovery should be essentially 100%, and result in a higher titration if (and it's a big if) a biasing acidic species was present in the first place.