Simultaneous Determination of Methamphetamine and Its Isomer N-Isopropylbenzylamine

[Dr. J]

This study sought best practice for accurate detection of completely legal and non psychoactive N-isopropylbenzylamine from its nearly identical chemical cousin, methamphetamine. Authors examined 8 samples from 2017/2018 determined to be methamphetamine and discovered that traditional testing methods including infrared spectroscopy, colloidal gold-based immunoassays, and GC/MS analysis were insufficient in distinguishing between the two.

This seems to confirm that synthesis using N-ISO is happening at the source, even in China. Moreover, if the advanced super scientific tests can’t tell the difference, using a reagent kit at the user level would be pointless.

Study Link

“Among drugs of abuse, methamphetamine (MA) is the second most popular illicit drug worldwide which has been listed as a category I psychotropic substance under strict state control in most countries. However, an isomer of MA, called N-isopropylbenzylamine (N-IBA), has often been used as the adulterant of MA in drug crimes due to their high similarity in structure (Figure 1), which easily resulted in the misidentification of N-IBA as MA in suspected samples. For example, the forensic science laboratory of the United States Drug Enforcement Administration (DEA) reported several cases of counterfeiting MA hydrochloride with N-IBA hydrochloride from 2007 to 2008.”

 

[Jabberwocky]

Definitely the paper we've all been waiting for. One of the things it also seems to point to, but did not clearly elaborate, is the indistinguishability of the product when it is a combination of MA and N-ISO. As I read it, the physical character (density etc) of pure MA and MA/N-ISO in combination versus the pure version of each was not directly commented on (but would have been evident in the tests used). That's important given the common view that re-rocked n-iso and MA makes obviously soft crystals with a particular opacity.

 

[4meSM]

Seeing N-ISO/N-NBA as an adulterant in Chinese meth samples is not too surprising, it's a fairly common chemical reagent and most of those chemicals are produced in China.
I don't think it's a significant problem nowadays though, at least according to the latest DEA reports. It might be more prevalent in other meth markets outside North America and Europe, maybe in countries closer to China and India?
(I haven't really looked into it)

I guess N-IBA could be difficult to quantify in some scenarios. But it doesn't seem like a super complex problem either, at least in my view, but I could be wrong since I don't know the ins-and-outs of the forensic field...

Here's an official DEA document from 2008 on the characterisation/identification of N-IBA and other alkylbenzylamines (as well as dimethylsulfone, AKA MSM) in meth samples.
Microgram Journal, June 2008
This relevant paper is on page 36. This is a direct download from erowid, I couldn't find an open access version of the paper. I think the DEA took down every single microgram report from their site (incluiding this one) and merged them into a single 1000+ page document...

 

[Dr. J]

Seeing N-ISO/N-NBA as an adulterant in Chinese meth samples is not too surprising, it's a fairly common chemical reagent and most of those chemicals are produced in China.
I don't think it's a significant problem nowadays though, at least according to the latest DEA reports. It might be more prevalent in other meth markets outside North America and Europe, maybe in countries closer to China and India?
(I haven't really looked into it)

I guess N-IBA could be difficult to quantify in some scenarios. But it doesn't seem like a super complex problem either, at least in my view, but I could be wrong since I don't know the ins-and-outs of the forensic field...

Here's an official DEA document from 2008 on the characterisation/identification of N-IBA and other alkylbenzylamines (as well as dimethylsulfone, AKA MSM) in meth samples.
Microgram Journal, June 2008
This relevant paper is on page 36. This is a direct download from erowid, I couldn't find an open access version of the paper. I think the DEA took down every single microgram report from their site (incluiding this one) and merged them into a single 1000+ page document...

Seeing N-ISO/N-NBA as an adulterant in Chinese meth samples is not too surprising, it's a fairly common chemical reagent and most of those chemicals are produced in China.
I don't think it's a significant problem nowadays though, at least according to the latest DEA reports. It might be more prevalent in other meth markets outside North America and Europe, maybe in countries closer to China and India?
(I haven't really looked into it)

I guess N-IBA could be difficult to quantify in some scenarios. But it doesn't seem like a super complex problem either, at least in my view, but I could be wrong since I don't know the ins-and-outs of the forensic field...

Here's an official DEA document from 2008 on the characterisation/identification of N-IBA and other alkylbenzylamines (as well as dimethylsulfone, AKA MSM) in meth samples.
Microgram Journal, June 2008
This relevant paper is on page 36. This is a direct download from erowid, I couldn't find an open access version of the paper. I think the DEA took down every single microgram report from their site (incluiding this one) and merged them into a single 1000+ page document...

Here’s the thing. I think we’re all familiar with the DEA report from 2008… it’s referenced in this study. This has a publish date of Feb 2021 and notes specifically that 8 samples that were deemed to contain meth using regular validation methods were not able to determine that some of those 8 — it wasn’t quite clear from the article— contained no meth. These were samples in American criminal drug cases/samples from 2017/2018.
At the very least, this confirms N-ISO is indeed involved/present jn “meth” currently circulating around the U.S. It also supports the numerous subjective reports of those who know something is off with batches out there. It was also unclear how easily updated testing methods could adequately confirm a majority N-ISO w/ small amount of d-meth or l/d meth. Of the 8, it concluded at least some of those contained only the inactive legal chemical.
I don’t know the sophistication of places like DrugsData to be able to detect and distinguish as from my browsing, I’ve not found a sample turned in that was reported as meth and instead was identified to be either entirely or completely the N-ISO. Reagent testing kits are reacting as would be expected because, again, they’re nearly identical chemically.
To me, this study seems to validate what I and others have long been claiming about the sad state of affairs in some/most of what’s out there right now. To be sure, I have no doubt that others are able to get hands on the real deal… since this is happening at the source—at least as sampled from China, that means it’s going to be this crappy mixture throughout all hands in the supply chain, increasing the likelihood that “your” bag isn’t as pure as thought. I dunno, seems like a bigger deal/confirmation/validation than I think you’re giving it credit for. Im not as well versed as others here, but I’ve been around the block and following this stuff for a few years and this is the most definitive article/study I’ve seen.

 

[4meSM]

Here’s the thing. I think we’re all familiar with the DEA report from 2008… it’s referenced in this study. This has a publish date of Feb 2021 and notes specifically that 8 samples that were deemed to contain meth using regular validation methods were not able to determine that some of those 8 — it wasn’t quite clear from the article— contained no meth. These were samples in American criminal drug cases/samples from 2017/2018.
At the very least, this confirms N-ISO is indeed involved/present jn “meth” currently circulating around the U.S. It also supports the numerous subjective reports of those who know something is off with batches out there. It was also unclear how easily updated testing methods could adequately confirm a majority N-ISO w/ small amount of d-meth or l/d meth. Of the 8, it concluded at least some of those contained only the inactive legal chemical.
I don’t know the sophistication of places like DrugsData to be able to detect and distinguish as from my browsing, I’ve not found a sample turned in that was reported as meth and instead was identified to be either entirely or completely the N-ISO. Reagent testing kits are reacting as would be expected because, again, they’re nearly identical chemically.
To me, this study seems to validate what I and others have long been claiming about the sad state of affairs in some/most of what’s out there right now. To be sure, I have no doubt that others are able to get hands on the real deal… since this is happening at the source—at least as sampled from China, that means it’s going to be this crappy mixture throughout all hands in the supply chain, increasing the likelihood that “your” bag isn’t as pure as thought. I dunno, seems like a bigger deal/confirmation/validation than I think you’re giving it credit for. Im not as well versed as others here, but I’ve been around the block and following this stuff for a few years and this is the most definitive article/study I’ve seen.

The National Drug Threat Assessment documents starting from 2016-2017 don't mention N-ISO as an issue (not sure about the ones before that time). Why wouldn't they mention it if it was such a big problem? They have known about it at least since 2008 (as shown in the microgram journal) and even developped a couple of analytical methods.
As shown on the graphs below, the quality of methamphetamine has increased a lot since 2008, and even more so in recent years. Nowadays (since ~2017) the average North American meth contains more than 90% dextromethamphetamine.

 

[Jabberwocky]

Unless the tests being used in the above give n-iso a false positive for being d-meth?

 

[Dr. J]

Unless the tests being used in the above give n-iso a false positive for being d-meth?

My thoughts exactly. The whole point of the study was to show that even standard confirmation tests were unable to identify the N-ISO. But, this begs the question of how they were able to spot the N-ISO back in 2007/2008.
Maybe they’ve improved their synthesis to either adjust the amount/composition of whatever the hell they’re sending north these days to make it no longer stand out as N-ISO the same way it did many years ago. And, despite the charts published by the government/DEA itself claiming purity is off the charts, why does it seem (at least to me and many of the reports I’ve read elsewhere online and those I’ve spoken with) are not shouting from the hills about this great, strong, even more pure product. Quite the opposite, in fact. Now, why would that be?? Not trying to be cute with that comment, it’s a genuine question….

 

[Jabberwocky]

My thoughts exactly. The whole point of the study was to show that even standard confirmation tests were unable to identify the N-ISO. But, this begs the question of how they were able to spot the N-ISO back in 2007/2008.
Maybe they’ve improved their synthesis to either adjust the amount/composition of whatever the hell they’re sending north these days to make it no longer stand out as N-ISO the same way it did many years ago. And, despite the charts published by the government/DEA itself claiming purity is off the charts, why does it seem (at least to me and many of the reports I’ve read elsewhere online and those I’ve spoken with) are not shouting from the hills about this great, strong, even more pure product. Quite the opposite, in fact. Now, why would that be?? Not trying to be cute with that comment, it’s a genuine question….

I don't have an answer on this at a general market level. However, as a moderator and active forum participant I see time and time again that many (most) people who turn up complaining about meth quality have one or more of the following qualities:

1. They are a long term daily user of at least a year (possible alternative explanation: tolerance)
2. They are taking dopaminergic psychiatric drugs (e.g. 2nd/3rd gen antipsychotics) (this drugs render the best meth near worthless)
3. They seem chauvinist about non-US produced meth (esp. mexican) in an almost racist way and, related to that
4. They want to emphasise they are in direct contact with domestic cooks (invariably 'bikers') who produce boutique amounts 'just like it used to be back in the day'

Now points 1 and 2 have applied to me at different times. With one year off both meth and psychiatric drugs a point of Asian meth sent me into an 18 hour whole body euphoric frenzy and obsessive sexual psychosis. Best high of my life. But as I kept using and then added psychiatric drugs back into the mix that euphoria and total frenzied high was quickly lost and only returned (to a lesser degree) when I took a month or longer off the product and the meds.

As to points 3 & 4 I would agree that there is something substantially different about the 2021 high from the 1990's high that must be explainable by some aspect of the product. Today's high is far less physically energising, has much more stereotypy and is far more prosexual than 30 years ago when we were all consuming something almost definitely made from pseudoephedrine but not (at least in Australia) called meth.

However, I don't understand how the product made from pseudo and the product made from P2P can provide such markedly different experiences if they are both the chemical methamphetamine HCL. That is except where pseudo is known to produce more d-meth and P2P to produce more racemic meth and while l-meth is argued to be not particularly psychoactive alone, it does seem to potentiate d-meth in different ways based on varying proportions of d- and l- in the product.

The presence of N-ISO would go a long way to explaining the difference between the 1990s and the 2021 experience as would some as yet unrealised difference in what is produced by pseudo routes and the P2P routes.

 

[S.J.B.]

This is not a reliable article. It's published in an obscure journal that isn't even related to the subject of the article. The references they gave as examples of methods for analysis of GC/MS samples of N-isopropylbenzylamine (refs. 25, 27, 28 ) did not, if fact, have anything to do with N-isopropylbenzylamine. This would never have passed legitimate peer review, but the Journal of Nanomaterials does not seem to be the kind of outlet that has legitimate peer review. The 2008 Microgram article posted by 4meSM makes it clear that methamphetamine and N-isopropylamine can be separated by GC, and their ionization patterns (these can be found in the Journal of Nanomaterials article but also from Wiley Subscription Services, Bio-Rad, and in the case of N-isopropylbenzylamine, in the Microgram article) are easily distinguishable from each other.

I would not worry about the DEA's capacity to analyze the N-isopropylbenzylamine content of methamphetamine samples.

 

[Jabberwocky]

Thanks @S.J.B. I didn’t stop to think it might be in a pay-to-publish predatory journal. But now I come to think on it, a lot of Chinese and Indian research does get published in such journals in every discipline.

I was only reading the discussion. I wouldn’t have any idea it the science was robust.

 

[4meSM]

Unless the tests being used in the above give n-iso a false positive for being d-meth?

It's a numbers game. The DEA has plenty of resources and they have tested many thousands of samples. Even if some samples were analyzed using obsolete equipment (or bad analytical methods) they would still have plenty of high quality results as well. They would definitely notice if n-iso was so prevalent.
They're even able to detect trace amounts of impurities in the sample, which allows them to figure out which synthetic route is currently being used by the cartels .

 

[S.J.B.]

Thanks @S.J.B. I didn’t stop to think it might be in a pay-to-publish predatory journal. But now I come to think on it, a lot of Chinese and Indian research does get published in such journals in every discipline.

I was only reading the discussion. I wouldn’t have any idea it the science was robust.

It's not that the actual experimental methodology and conclusions were wrong. It's just that they framed it in a way that overstated the importance of what they were contributing (and added irrelevant references, which is the greater sin). They pretty much were just screening LC conditions to get better separation. They are definitely not the first lab to do so for these two compounds, and if it hasn't been published before it's most likely because it's such a routine thing that a proper journal wouldn't consider it publication-worthy (which is why they had to go for this obscure -- not necessarily predatory, but definitely of lax standards -- journal in a different field).

 

[sekio]

My thoughts exactly. The whole point of the study was to show that even standard confirmation tests were unable to identify the N-ISO. But, this begs the question of how they were able to spot the N-ISO back in 2007/2008.
Maybe they’ve improved their synthesis to either adjust the amount/composition of whatever the hell they’re sending north these days to make it no longer stand out as N-ISO the same way it did many years ago.

if your analysis methods are more complex than vaporizing some in a meth pipe and looking at the crystals, it should be trivial to seperate the two on a properly configured GC. I bet you could even find a TLC method to analyze the two,

there is something substantially different about the 2021 high from the 1990's high that must be explainable by some aspect of the product. Today's high is far less physically energising, has much more stereotypy and is far more prosexual than 30 years ago

And you don't think 30 years of drug use might be the factor here, rather than the meth?

[N-isopropylbenzylamine] is a fairly common chemical reagent

It's not what I would call "common", it's not really used for much in the lab.

I would assume there's at least some competition between dealers who get different supply lines, meaning anyone cutting wirh N-iso has to go out of their way to spend money to get a cut that will make the dealer's product inferior to others',

I also know that some meth users are never satisfied with their meth, and assume that it must be cut when they have a less then awesome experience (low blood sugar, bad environment, not enough sleep etc are all factors that make for a less enjoyable time).

 

[Gaffy]

For thé last Time, npropylbenzylamine has nothing to do with meth, it's two complète différent moles

 

[Nagelfar]

I also know that some meth users are never satisfied with their meth, and assume that it must be cut when they have a less then awesome experience (low blood sugar, bad environment, not enough sleep etc are all factors that make for a less enjoyable time).

I would wager this to be the case as much as 99% of the time (I may be exaggerating – though considering the degree to which every user puts the responsibility of the high entirely onto their drug & not on the plasticity of their selves - i.e. they are a dynamic lifeform capable of, and even undergoing continual, change: the best possible quality controlled chemical, simple is not, wholly devoid of these factors)

 

[4meSM]

It's not what I would call "common", it's not really used for much in the lab.

Yeah maybe common isn't the right word... But what I meant is that it's just an N-substituted aklylbenzylamine, it's a pretty simple and straightforward molecule that can be bought from most chemical suppliers.

TBH I was kind of trying to give them the benefit of the doubt. I personally don't see any difficulties with the separation of meth and "n-iso" from a drug sample, either via GC or LC (unless you're using very outdated equipment).
But there may be some issues regarding the LOQ (limit of quantification) if you're analyzing more complex samples such as bodily fluids, depending on your column and analytical method.

Everyday there's a new thread about fake meth, I was open minded at first but now I think it's just "groupthink". It has become a pretty widespread drug myth, I wouldn't be surprised if reddit had something to do with this.

 

[Jabberwocky]

.

Everyday there's a new thread about fake meth, I was open minded at first but now I think it's just "groupthink". It has become a pretty widespread drug myth, I wouldn't be surprised if reddit had something to do with this.

A few years ago some guy launched his own ‘research paper’ on n-ISO and meth on Reddit and it took off from there. The paper is still circulating. I think a lot of people who take pharma drugs that affect the dopamine system are getting less bang out of their buck with meth and not connecting the dots. As well as the fact that quality occasionally does vary over time.

 

[4meSM]

A few years ago some guy launched his own ‘research paper’ on n-ISO and meth on Reddit and it took off from there. The paper is still circulating. I think a lot of people who take pharma drugs that affect the dopamine system are getting less bang out of their buck with meth and not connecting the dots. As well as the fact that quality occasionally does vary over time.

Yeah I think I've seen that thread on reddit.
Now it's really getting out of control, everyone thinks they have "n-iso"...
I think it does a disservice to harm-reduction, more and more side effects are being attributed to n-iso. As if d-meth was completely free of side effects and 100% consistent every single time.

We know most cocaine is cut with levamisole, that north american heroin often contains fent or other synthetic opioids, etc... There's a ton of evidence, you can even go to drugsdata.org and see a bunch of test results.
But "n-iso"? There's an extreme lack of evidence of it being so widespread (or even having any psychoactive effects whatsoever), yet so many meth users see it as a fact.
I literally haven't seen a single lab report confirming its precense in a sample of supposedly fake meth.

 

[Dr. J]

Yeah I think I've seen that thread on reddit.
Now it's really getting out of control, everyone thinks they have "n-iso"...
I think it does a disservice to harm-reduction, more and more side effects are being attributed to n-iso. As if d-meth was completely free of side effects and 100% consistent every single time.

We know most cocaine is cut with levamisole, that north american heroin often contains fent or other synthetic opioids, etc... There's a ton of evidence, you can even go to drugsdata.org and see a bunch of test results.
But "n-iso"? There's an extreme lack of evidence of it being so widespread (or even having any psychoactive effects whatsoever), yet so many meth users see it as a fact.
I literally haven't seen a single lab report confirming its precense in a sample of supposedly fake meth.

I would direct you to page 36 of this link. It’s a bit dated but this is proof from the DEAs own analysis that there is truth to this happening “in the wild” … if it was found in 2007/2008, what’s to say it wouldn’t still be happening?

https://erowid.org/library/periodicals/microgram/microgram_journal_2008-1.pdf

 

[Jabberwocky]

In laboratory testing over 6000 separate methamphetamine seizures ranging in size from hundred of kilos being imported to grams seized on the street, the Queensland police detected n-iso in only a handful of samples (less than 20 I can’t remember the exact number). They found about as many as they found meth contaminated with seroquel. If it’s a problem it’s an American problem not an Australian one. More than 95 % of seizures were pure meth or meth cut with inert substances. That’s not to say there wasn’t a lot of l-meth in there.