For over forty years, methamphetamine-using communities have been speculating why some batches of meth seem qualitatively different than others. When we started working in this field in the 1990s, the claim was that l-meth, solvents, and synthesis impurities were the culprits.
Since around 2010, the DEA’s policies have resulted in most methamphetamine inside the United States coming from large manufacturers outside the US. In the ensuing years, some have claimed that the unpleasant effects of street meth in the US are a result of meth containing N-Isopropylbenzylamine (isopropylbenzylamine; N-IPBA; “N-iso”) [PubChem]. It is a common enough claim that many skeptics have called N-iso the new meth boogeyman.
The most common claims about isopropylbenzylamine are that it is present in combination with meth, and causes more paranoia, psychotic ideation, and worse hangovers. It’s also blamed for effects atyptical for stimulants, such as lethargy and “brain fog”, 1-3 days into a meth-using session.
We’ve been asked about N-iso many times between 2019 and 2022. We purchased the certified reference lab standard for isopropylbenzylamine twice in the last two years in order to run experiments to check our methods. We have repeatedly confirmed that zero (0) meth samples analyzed by DrugsData to date have contained it:
https://drugsdata.org/results.php?substance1=94&substance2=2036
Erowid’s DrugsData reported those findings to the people submitting the samples in question, and on the corresponding entries on DrugsData.org. Up until now, we haven’t specifically pointed out publicly that multiple submitters have claimed that isopropylbenzylamine could be present in their methamphetamine and that our findings have not substantiated their claims.
Our results caused others to ask us more and more pointed questions about how sure we were that N-iso wasn’t in the meth we tested. So we dug deeper. After re-analyzing and examining the GC/MS data for more than a dozen samples submitted to DrugsData for which the submitter was certain their meth sample contained isopropylbenzylamine, we’ve still seen no results where this is the case.
Out of 271 samples containing methamphetamine analyzed between January 2019 and July 2022, none contained isopropylbenzylamine:
https://drugsdata.org/results.php?s=methamphetamine&search_field=substance&y1=2019&y2=2022
Re-examining Our Findings
In late 2020, we ran several samples of alleged meth + N-iso and they came back meth only. We bought the reference standard and tried slightly-modified procedures using this standard. It seemed to us that meth + isopropylbenzylamine resolved easily via GC/MS. That is to say, meth and N-iso were easily differentiated in our lab. They are close, but we deal with much harder problems all the time.
In May 2022, D.M. contacted us to point out a paper that said it is possible that mixed samples containing both meth and isopropylbenzylamine could cause analysis to fail to see one or the other. Essentially, they claimed our previous findings might be wrong because one of the two could hide inside the GC curve of the other and then elute (come out) at such a similar time into the Mass Spectrometer that our software would report only one of the two chemicals.
That paper is Luo Y, et al. (2021) “Simultaneous Determination of Methamphetamine and Its Isomer N-Isopropylbenzylamine in Forensic Samples by Using a Modified LC-ESI-MS/MS Method”. (ResearchGate Link) The authors write:
“However, the two compounds [methamphetamine (MA) N-isopropylbenzylamine ([N-IPBA]) ] were hard to be effectively discriminated by GC/MS when there was a large concentration difference between them. Because the retention times for MA and [N-IPBA] chromatographic separation were very close due to their high similar chemical structure, the compound with high concentration would interfere with another one with low concentration as the two compounds yield similar ion fragments for detection [25].”
Note the relevant claim in their paper is actually cited to someone else and is not something these authors themselves demonstrate in their article. The original citation (Xuan J et al 2015) is a paper in a Chinese journal that we’ve been unable to locate.
Given this new, reasonably specific claim from a 2021 paper, despite having done it before, we purchased a new isopropylbenzylamine reference standard, this time from a different chemical supplier. Unsurprisingly, it matched exactly the previous standard and also matched the GC/MS data in the main public/research/commercial/forensic libraries.
A Series of Experiments
We mixed pure d-meth with N-IPBA at 1:1, 1:10, 1:100, 10:1, and 100:1 ratios. In all of the conditions, our setup showed isopropylbenzylamine as clearly distinct from methamphetamine. They would not be mistaken for one another or lost, even way below 1:100. Our standard procedure involves methanol run through an Agilent GC/MS 5973 MSD with the GC column being an HP-5ms Ultra inert (5%-phenyl)-methylpolysiloxane. Unless you’re a lab tech, that won’t mean anything to you, but it’s a fairly normal setup for doing drug work like this and it’s well suited to analyzing chemicals of this type.
The GC output pictured above is from N-IPBA (“N-iso”) (1 part) mixed with meth (100 parts). The other main peak (9.972) is a calibration chemical. The slightly messy baseline to the right of the meth peak is related to the way that the salt versions (Meth HCl, for instance) of the two drugs differ in their elution times in the GC column. This example graph is after several tests in a row using different ratios of meth and isopropylbenzylamine. It is common when running methamphetamine salts to end up with a little right-side, baseline noise after the sharp freebase meth peak.
Methamphetamine and isopropylbenzylamine do elute at similar times, but using our procedure, they are clearly distinct. Note in the GC image the sharp valley between the N-iso and meth peaks: N-iso at 3.4777 minutes and meth at 3.687 minutes in this run.
And they always have clearly distinct Mass Spectra (MS), so they simply don’t get confused at our lab. If a lab were running a different column and procedure that isn’t targeted for doing work on methamphetamine and related drugs, it’s easy to imagine other procedures and rigs where an analytical chemist could confuse one with the other.
As of August 2022, DrugsData’s lab has found isopropylbenzylamine in eight samples total, ever, and two DEA-tested samples are republished in our database:
https://www.drugsdata.org/results.php?search_field=substance&s=Isopropylbenzylamine
It is Erowid’s view that most negative effects from meth use are a result of lack of sleep combined with irregular water and food consumption. People mistakenly attribute differences in experience from time to time to differences in impurities in the drugs, instead of other factors such as diet, mood, context, electrolyte levels, and physical rest.
It’s certainly possible that a sample analyzed in DrugsData’s lab in the future could contain both methamphetamine and isopropylbenzylamine. We feel certain that for such a sample, lab results would clearly show this to be the case.
—earth, Sylvia, Fire, Roi
I love this article and tend to agree… But what about the articles reporting synthesis impurities such as butylamphetamine popping up in samples over recent years?
Here’s a link to a BL thread with relevant info.
https://bluelight.org/xf/threads/maybe-the-meth-has-changed.919721/
Is it possible to look for these impurities? It seems at least butylAmp would lessen some of the positive effects based on the scant pharmacological data present.
We could be looking at a combination of new synthesis impurities and high availability of cheap product leading to the supposed change many users claim today
This specific experiment was designed ONLY to look at the question of whether we were missing n-iso when we analyzed samples of methamphetamine. This is something that’s come up many times over the years and we are now sure that we can see n-iso when it’s mixed with meth. You’re absolutely right there might be other impurities or substances we are not seeing.
If we have a specific list of substances for which there are available reference standards (CaymanChem, Sigma, etc) we can buy those standards and run similar experiments. The most obvious three are 1:10; 1:1; and 10:1 . If we can reliably see the impurities in those conditions, great. If we can’t, that’s importable information.
We use a very standard method in the field of analytical chemistry (aka forensic toxicology) to look at meth and related drugs. We dissolve in anhydrous methanol and run it in a very normal GC coil with a standard heat ramp parameter. Meth shows up very easily. But some substances simply don’t gasify very well. This is a known weakness of GC/MS and something that every person who understands the technology knows. There are workarounds for many substances, but for some one needs to use another type of testing such as LC/MS or HPLC. Both of those technologies also have ‘blind spots’ where some substances simple do not show up.
For LC (liquid chromatography), the substance must have a strong solubility in the given solvent. If one optimizes for meth and related compounds that dissolve nearly 100% in methanol, but an impurity only has a 1% solubility in room temperature methanol, then it’s totally possible to miss that impurity because it disappears into the background noise.
For HPLC, the issues are similar. There are just certain things that don’t dissolve in the same way as other chemicals and they can be missed — unless one knows you’re looking for them.
We use GC/MS almost exclusively for DrugsData samples, but for the substances known not to GC very well, we use wet bench chemistry methods known as ‘derivitization’: simple reactions that attach something to the substances that allow them to gasify and thus show up in the GC.
So, please email us a list of possible impurities and we’ll plan a new set of experiments to see if they would show up using our standard methods or not.
What about the levels of methylcathinones? Manganese dioxide could explain all the symptoms including erectile dysfunction — around here it seems to be the case with every male middle aged or older meth user. The meth around here does not taste like it did in the early 2000s nor doesn’t crystallize the same nor is it the same color. It turns brownish rather fast and tends to have a nutty flavor.
Thank you for your excellent work. i really appreciate your willingness to consider your methods when questioned along with your transparent intent to provide good science.
In your tests, you used the ratios of d-meth to n-iso at 1:1, 1:10, 1:100, etc. Thing is, most if not all the meth we get here in the US is a racemic mix of 50% d-meth and 50% l-meth, or so I’ve been told. I don’t know if that would have any affect on the testing or not.
Another point is the ratios used should be inversed. Most meth users prescribing to the iso cut theory believe the meth they are getting now is around 50% racemic meth or 25% d-meth and 25% l-meth and 50% n-iso or 1:1, I guess?
What if the ratio was 25% n-iso or 35% n-iso? Your testing was for n-iso in excess to meth. No one believes their meth is 1:10 meth to n-iso. But the other way around seems plausible. I’m not a scientist or chemist but it seems to me that your test parameters were flawed from the start.
The article describes that we designed and implemented a series of tests to do exactly what you’re asking. We proved that we can reliably detect n-iso (N-Isopropylbenzylamine) at any ratio, whether the amount of n-iso exceeds that of methamphetamine, equal to, or lower than the amount of meth.
We did not address the issue of d-meth or l-meth in this series of experiments, but that would have zero effect the outcome because our GC/MS method has d-meth and l-meth appear identically. It’s too technical to describe why, but you just have to trust that this is just how GC/MS works with pure d-meth, pure l-meth, or any mixture of the two. They elute at identical times and their mass spectrums are identical. There are methods to make them appear different in GC, “derivitizations”, but that doesn’t matter for the specific experiment we were doing here.
We can see N-Isopropylbenzylamine as separate (but close) to methamphetamine in elution time and they have distinct mass spectrums. So both analytical tools that make up a GC/MS can tell the difference between n-iso and methamphetamine.
Our lab has so far never seen any sample of methamphetamine with *any* n-iso. We have asked folks on Reddit who use the home separation method to send us their samples where they believe they have separated the two substances, but we have had no takers of free analysis so far.
If you have used the “How to Separate N-iso Easily; and Why You Should” method and have had results as described where you start with crystalline material, do the procedure, and wind up with two separate crystalline materials: we want to test all three. We want a sample of the un-separated material and samples of the “garbage” and the “good stuff”, marked as such. Please email info@drugsdata.org to discuss free analysis of your materials.
I think the claim that most negative effects from meth use are a result of lack of sleep combined with irregular water and food consumption is a bit out there. I do agree that the whole N-iso story is mostly false. But people don’t have a chemistry background, they hear something that sticks and run with it. It makes some sense chemically and so this is now almost a meth meme.
In reality, because of the purification of the racemic meth, cartels and other big orgs now have this super pure d-meth which they could cut 80% and even then sell as “premium grade”, I don’t think they really do unless you are close to the source. And they have left-over l-meth, which they also are able to sell, apparently. You get batches of 98% l-meth and 2% d-meth, it’s PURE METH, that’s the funny part about it, it’s not even a lie. I think it’s hard for people to grasp this and it’s hard to figure out anyway. Ok I’ll buy a sample but let me first do some enantiomeric analysis – that doesn’t fly well at your local meth house.
Ok, so new theory (to us) being proposed here is that the meth is “pure”, but its not racemic and the variations in experiential effects might be related to different portions of d versus l enantiomers. Our main methods don’t differentiate, but we can. If someone has some meth they think has an n-iso problem or something similar, we could look at it for enantiomer proportions.
Thank you so much for this fantastic, succinct post. This is very helpful.
Here in Aotearoa New Zealand our drug checking services are seeing increased reports of unexpected effects from meth but we are also seeing more confirmed presence of N-Iso in methamphetamine samples. Primarily analysed with FTIR but also confirmatory testing with GC/MS.
We are currently trying to determine what the actual effects and risks of N-Iso are. There is very little info available which is coupled with confirmed presence of N-Iso. If anyone has any info to inform that question, please share!