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The N-Isopropylbenzylamine “myth” and developments in Drug Testing

Jabberwocky

Frumious Bandersnatch
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Nov 3, 1999
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There are many people on this forum far more expert then me about what follows. I look forward to their comments and corrections if I’ve got any of this wrong.

Isopropylbenzylamine (n-iso) is a chain isomer of methamphetamine. It is known in the scientific literature under numerous other names. In their salt (HCL) forms, the two substances appear similar in terms of crystalline structure and melting point although shard density and opacity are sometimes (erroneously) claimed to be a means to differentiate them. It is claimed that reagent tests cannot differentiate the two substances. The substance has achieved near mythical status amongst methamphetamine users who blame either claim it has no psychoactive effects or induces negative physical sided effects such as nausea and headache and a general feeling of being “sketched out”. It is very widely advertised for sale by international RC and other chemical suppliers - suggesting there is a significant illicit market for it. It is also claimed by some Chinese researchers that n-iso gives a false positive for meth on the standard colloidal gold urine test.

An extensive search of the internet using multiple names for n-iso reveals only a very small number of primary sources conclusively proving methamphetamine and n-so being found together. I would guess less than a dozen mentions. However, there is an observable discourse about methamphetamine and n-iso that takes it for granted that n-iso is a not uncommon adulterant in meth supply. This speculative discourse is evident even in reports at the level of The UN office on Drugs and Crime. Primary sources include significant amounts of pure n-iso being used to bulk out methamphetamine shipments (US), large amounts of n-iso being imported by known methamphetamine distributors (Aus), and a small number of methamphetamine seizures (approx 8 from 6,000 tests) testing positive for n-iso contamination (Aus). Proponents of the n-iso theory argue that this is because n-iso is so similar to meth that the two substances are so similar they cannot be differentiated by drug testing technology.

A recent Chinese article (https://www.hindawi.com/journals/jnm/2021/6679515/) has added to the discourse because it strongly implies that Gas Chromatography/Mass Spectrometry (GC/MS) is not capable of effectively differentiating the two substances. It also implies that GC/MS is the only viable method to differentiate the two substances. It then proposes a new GC/MS technique that better differentiates the two and tests it on 8 samples seized by Chinese police. However the literature and some online chemical databases suggest their claims may be exaggerated. Differences between spectra results for both substances can be seen on PubChem

Observable Differences Between Meth and N-ISO

While the NMRI spectra are clearly different NMRI is not commonly used in drug testing

N-ISO NMRI Spectra (on Varian CFT-20 instrument)


Meth NMRI Spectra (Varian)


On the other hand, the IR spectra shows clearly different results.

N-ISO AT-IR Spectra


Meth AT-IR Spectra


Finally, the Raman spectra are also distinct

N-ISO Raman Spectra


Meth Raman Spectra


Why Is This Significant?

There are a range of ways of testing drugs and different organisations and agencies use techniques from the cheapest one-shot reagent test up to GC/MS machines costing a million dollars or more. In many jurisdictions GC/MS is mandated as the only legally admissible evidence in drug cases. In some jurisdictions GC/MS and isotope analysis is used regularly because it provides intelligence on what precursors were used and the geographical location of production techniques and the specific of those production techniques themselves. So this level of testing is happening around the world. The FBI and the Australian Federal Police maintain programs to do it purely for high level intelligence gathering.

But this level of testing is also becoming cheaper and portable and available to harm reduction organisations either on their own or in partnership with commercial private-sector labs.

A mass spectrometer can be obtained from $5,000 up though it requires a lot of consumables and an expert operator and is not practical for an HR clinic. However many services are available that do use it. Wedinos for example uses both NMRI and GC/MS to analyse samples and could therefore presumedly differentiate meth and n-ISO. They have accepted one sample claimed to be n-iso, but upon testing it proved to be meth. They also regularly use NMRI to detect analogues of different drugs in mixture.

An IR spectrometer can be obtained for about $5,000 and is common in pharmaceutical labs. It is capable of differentiating isomers. In Australia the harm reduction organisation Pill Testing Australia offers a IR drug testing service. Although they emphasise pills they state that “if you can consume it, we can test it” and will test powders and shards. However they are set up for testing at festivals and don’t seem to have a walk-in or mail-in service. IR treating is non-destructive so technically you can consume your drugs if they test ok.

Raman spectrometry is relatively cheap and highly accurate. It will identify an aqueous solution of only 1% meth in a plastic bag. Like IR spectrometry none of the field test results I looked at ever gave a false positive, unlike reagent testing which give false positives frequently. However it is known that some US police agencies use Ramen spectrometers (Kentucky was one discussed in the literature). However, field testing showed that lower end machines such as those used by police are unable to generate a result on substances that exhibit a high degree of fluorescence. However higher end machines were shown to be able to clearly differentiate between synthetic cathiones based on regioisomer positions on the phenyl ring. Raman testing is also non destructive. There is one study that empirically demonstrates the feasibility of IR spectrometry to differentiate meth and n-ISO (https://onlinelibrary-wiley-com.ezp...au/doi/full/10.1111/j.1556-4029.2010.01336.x#). However the study indicates the ability to do so is dependent on the relative proportions/concentrations of meth and n-iso in the sample. However this study used a low power IR spectrometer, and other studies show that higher power machines are far more discriminatory.

Bottom Line

There are numerous theoretical and empirically validated testing mechanisms available to both law enforcement and the general public that are able to differentiate between methamphetamine and n-isopropylbenzylamine. It may be possible that such testing has been conducted and the negative presence of n-iso has simply not been reported (negative results that do not prove a hypothesis are commonly not written up for scientific journals). Given the online noise around n-iso once would expect we’d pretty soon hear about a positive result. More likely though is the possibility that no-one has bothered to use the above mentioned technologies to field test suspected contaminated meth.

I encourage those people who believe in the n-iso phenomenon to contact publicly accessible drug testing agencies and enquire whether they employ these technologies and whether their equipment is sufficiently sensitive to differentiate the two substances. This may not be a productive avenue because not all testing machines are created equal and not all agencies would want to do a custom test outside their normal protocols. However, even making the enquiry would be an improvement on the unsubstantiated assertions n-iso is in every second bag of meth out there.
 
A seizure of isopropylbenzylamine from 2008 (US) and a blog entry from someone who wanted to test the physical properties of isopropylbenzylamine -so he purchased DNM meth assuming it to be isopropylbenzylamine- these are the two most commonly cited sources proving 110% that n-iso is the reason meth isn't the same as it was when they started using.
 
There is no doubt that there are a large number of sources for it on the internet. Many may be scams, but it seems there must be a large market for it. But they are sub-commercial quantities. If it’s not low level dealers buying it’s hard to imagine who else might want it. But the cartels definitely aren’t buying it 250g at a time online!
 
Yeah, that Chinese article came up in another thread, it's garbage that wouldn't have gotten through proper peer review.

By "NMRI" you meant NMR (nuclear magnetic resonance), although it is indeed the same technology as MRI (magnetic resonance imaging). The spectra you posted seem to be simplified versions of the actual spectra, and only the most downfield peak is showing. Regardless, the conclusion is correct: the NMR spectra of methamphetamine and N-isopropylbenzylamine are easily distinguishable. Here are the proton NMR spectra of methamphetamine and N-isopropylbenzylamine freebase, respectively, in chloroform-d:

methamphetamine_proton_nmr.jpg


n_isopropylbenzylamine_proton_nmr.jpg
 
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Yeah, that Chinese article came up in another thread, it's garbage that wouldn't have gotten through proper peer review.
Avoid producing yet more garbage which wouldn't pass proper peer review: When making claims comparing proton NMR try posting 2 proton spectra not one proton and one 13C spectra.

The upper spectra you posted is a 13 carbon NMR the lower is 1H proton.

By "NMRI" you meant NMR (nuclear magnetic resonance), although it is indeed the same technology as MRI (magnetic resonance imaging). The spectra you posted seem to be simplified versions of the actual spectra, and only the most downfield peak is showing. Regardless, the conclusion is correct: the NMR spectra of methamphetamine and N-isopropylbenzylamine are easily distinguishable. Here are the proton NMR spectra of methamphetamine and N-isopropylbenzylamine freebase, respectively, in chloroform-d:

methamphetamine_proton_nmr.jpg


n_isopropylbenzylamine_proton_nmr.jpg
 
Can u identify the peaks? Past 7ppm are aromatics. ~4ppm are N-H peaks. Have fun with the others.
 
The difference between the two 1H Spectra can be viewed here:

D-Meth HCL: https://spectrabase.com/spectrum/84o8jLZSmV9

N-ISO HCL: https://spectrabase.com/spectrum/Bp4LghXaC7o

We’re not doing a peer-review article. We’re just trying to prove the point that a lab using NMR spectra analysis (in this case) could easily differentiate d-meth HCL from n-ISOv HCL.. I don’t know how to interpret spectra results, but they clearly look different. It would be useful if someone could explain how these results could or could not confirm the presence of n-iso in a meth sample.
 
Well yeah. You would use chromatography if the samples were mixtures. Like a chromatography column. Then NMR. These samples are pure compound in the spectra. One peak is solvent, one is for water. The rest are for the isopropyl hydrogen or n-methyl hydrogen. And then N-H and aromatics. I could ID the peaks, it would just take some thinking.

This is on my shelf.

9780470616376_l.jpg
 
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The difference between the two 1H Spectra can be viewed here:

D-Meth HCL: https://spectrabase.com/spectrum/84o8jLZSmV9

N-ISO HCL: https://spectrabase.com/spectrum/Bp4LghXaC7o

We’re not doing a peer-review article. We’re just trying to prove the point that a lab using NMR spectra analysis (in this case) could easily differentiate d-meth HCL from n-ISOv HCL.. I don’t know how to interpret spectra results, but they clearly look different. It would be useful if someone could explain how these results could or could not confirm the presence of n-iso in a meth sample.
I can't see the spectra right now but you should be able to differentiate between those 2 molecules.
NISOMETH.jpg


Meth: the 2 CH3 groups are not chemically equivalent. The blue hydrogens couple with the pink hydrogen so the signal should be a doublet accounting for 3 protons. On the other hand, the red hydrogens do not couple with the pink one, plus this CH3 group is directly adjacent to the nitrogen atom, so the red hydrogens should give a different signal (with a different chemical shift).

n-ISO: the 2 CH3 groups are basically chemically equivalent (though there may be some variations in the case of the HCl salt depending on the experiment conditions). They (the green hydrogens) couple with the pink one so the signal should be a doublet accounting for 6 protons.
 
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While isopropylbenzylamine has most certainly been used as a cutting agent (or outright sold as meth) due to it's similar physical properties, it is those properties which greatly limit it's potential for wide-scale use.

N-Iso is relatively costly, bulky in crystal form, may field test as meth (of which it is an isomer), and for all of those reasons and more - is difficult to import / smuggle.

The growing popularity of online sales are most likely a self-fulfilling prophecy of methamphetamine users and their awareness-raising campaigns.

I think we've concluded that the only surefire way to identify isopropylbenzylamine in samples sold as methamphetamine, is to give it to people who got 'dat 🔥🔥' back in the good ol' days (somewhere between the early 80s and 2019 - coincidentally, whenever that particular scientist started using).
 
Avoid producing yet more garbage which wouldn't pass proper peer review: When making claims comparing proton NMR try posting 2 proton spectra not one proton and one 13C spectra.

The upper spectra you posted is a 13 carbon NMR the lower is 1H proton.
Look a little closer, particularly at the chemical shifts.
 
LOL what the actual fuck?

Varian CFT-20?

that shit is like like 50 years old. No literally. It may very well be THE OLDEST commercial NMR.

also what the fuck is with all these right to left spectra (reference std on the right with greater shift on the lift)

I never saw a single example of that, either in textbooks or any NMR aquisition software, until recently.
 
While isopropylbenzylamine has most certainly been used as a cutting agent (or outright sold as meth) due to it's similar physical properties, it is those properties which greatly limit it's potential for wide-scale use.

N-Iso is relatively costly, bulky in crystal form, may field test as meth (of which it is an isomer), and for all of those reasons and more - is difficult to import / smuggle.

The growing popularity of online sales are most likely a self-fulfilling prophecy of methamphetamine users and their awareness-raising campaigns.

I think we've concluded that the only surefire way to identify isopropylbenzylamine in samples sold as methamphetamine, is to give it to people who got 'dat 🔥🔥' back in the good ol' days (somewhere between the early 80s and 2019 - coincidentally, whenever that particular scientist started using).
That would be me. I was also manufacturing it back in the 90s. RPI so I’m not a chemist I never claimed to be one but I will tell you this using Isopropyl alcohol 91% pouring it hot on top of powdered broken down samples that I took from several different sources and letting it sit and evaporate slowly it separates the n-ISO from the Methamphetamine. As a matter fact I had one .06g beveled square princess cut diamond crystal that formed in the mother liquid and of course the racemic collects on the house side of the alcohol on the sides of the glass like powdered sugar
 
While isopropylbenzylamine has most certainly been used as a cutting agent (or outright sold as meth) due to it's similar physical properties, it is those properties which greatly limit it's potential for wide-scale use.

N-Iso is relatively costly, bulky in crystal form, may field test as meth (of which it is an isomer), and for all of those reasons and more - is difficult to import / smuggle.

The growing popularity of online sales are most likely a self-fulfilling prophecy of methamphetamine users and their awareness-raising campaigns.

I think we've concluded that the only surefire way to identify isopropylbenzylamine in samples sold as methamphetamine, is to give it to people who got 'dat 🔥🔥' back in the good ol' days (somewhere between the early 80s and 2019 - coincidentally, whenever that particular scientist started using).
n-ISO is a liquid in original form, and Its sold in 50 gallon liquid drums which I presume is what they have been busting people with lately
 
n-ISO is a liquid in original form, and Its sold in 50 gallon liquid drums which I presume is what they have been busting people with lately
It is also sold on designer crystal forms from Chinese manufacturers who produce it in a wide variety of crystalline shapes - needles to nuggets. They also tinker with it and pre-blend it with MSM to move the melting point as close to meth as possible.

That said, there is zero evidence you get in your Aussie meth.
 
It is also sold on designer crystal forms from Chinese manufacturers who produce it in a wide variety of crystalline shapes - needles to nuggets. They also tinker with it and pre-blend it with MSM to move the melting point as close to meth as possible.

That said, there is zero evidence you get in your Aussie meth.
I don’t live in Australia mine comes from the Mexican cartels, im in America. And I had one of them actually today admit to it
 
That would be me. I was also manufacturing it back in the 90s. RPI so I’m not a chemist I never claimed to be one but I will tell you this using Isopropyl alcohol 91% pouring it hot on top of powdered broken down samples that I took from several different sources and letting it sit and evaporate slowly it separates the n-ISO from the Methamphetamine. As a matter fact I had one .06g beveled square princess cut diamond crystal that formed in the mother liquid and of course the racemic collects on the house side of the alcohol on the sides of the glass like powdered sugar

This is not in any way a form of separation or analysis. Crystallization from a solvent can occur at different times in different places in the container with varying size/shape crystals.

I could easily explain this away as the small crystals on the side occurred during the major drop in heat while the crystal grew during a longer more drawn out phase of cooling.

While it is possible to separate substances like this based on solubility you’d then need each analyzed to know if they are different substances or the same.

-GC
 
I don’t live in Australia mine comes from the Mexican cartels, im in America. And I had one of them actually today admit to it
You were talking to a Mexican cartel chemist working in a super lab producing hundreds of kilos of meth every week?

Fuck, what an awesome connect! What else did you learn?
 
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