It’s been noticeable that most (nine out of ten) ketamine samples analyzed by DrugsData since March 2019 have contained 1-[(2-Chlorophenyl)(methylimino)methyl]cyclopentanol (CAS #6740-87-0), or “Ketamine Precursor A”. Synonyms of this substance in the literature include “Ketamine Related Compound A” and “Ketamine Impurity A”.
Since 2019, only 37 ketamine samples have been analyzed by DrugsData that contain only ketamine (zero in 2022). An additional 297 sample contained Ketamine + Ketamine Precursor A, and 19% of these 297 samples also contained MSM.
Ketamine Precursor A has been notably present in black market ketamine, but should not be present in commercial, pharmaceutical ketamine inside the United States or Europe.
Ketamine Precursor A is not considered harmful, just a waste of mass and chemical. We do not know of any good research on its toxicity, but unfortunately, most drug research that shows “no effect” doesn’t get published. If it were super toxic, we’d probably know about it.
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:
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:
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:
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.
The unidentified substance has mass spectrum major ions at 96; 217.1; 174.1 with an elute time at around 10.7 in our main setup.
This small sample of white powder in a blue bindle was submitted to DrugsData via research partners we’re working with to do lab confirmatory testing. Besides Fentanyl and 4-ANPP, it contained a third chemical we were initially unable to identify.
We publish the Mass Spectrum (MS) images for substances we need help identifying. A colleague at UNC’s drug checking project examined this substance’s image and reached out with some clues, which put us on the path of figuring out what its structure is.
One of our top volunteer analytical chemistry experts, Eddee, found a close match in Wiley’s 2020 “Designer Drugs” library, a library that our DrugsData lab doesn’t have. The close (though not perfect) match is for ethyl-despropionyl-fentanyl (ethyl-4-ANPP). Our experts (thanks, Koby!) guess that this is likely to be much less potent than fentanyl and might not be very active, similar to despropionyl-fentanyl (4-ANPP).
There’s a PubChem page for it, but no CAS number yet:
Eddee speculated that the difference between our sample and the Wiley library match might not be meaningful. In the following image, which is pretty complex to look at, the top chemical is our DrugsData sample’s unidentified substance. The lower chemical is the Mass Spectrum for the presumptive ethyl-despropionyl-fentanyl. The middle part of this image is a comparison of the two, with our sample on the top (lines going up) and the proposed match on the bottom (lines going down). You’ll need to open it in a new tab to see the detail, it’s dense stuff.
What you’re looking at are the relative heights of the largest peaks (vertical lines), aka the “ions”. Mass spectrometry (MS) relies on breaking up a chemical with a high energy stream of electrons; Erowid’s DrugsData lab uses an “electron spray” method. The resulting bits are highly charged ions that get spun through a magnetic whirlwind inside a specialized detector. The heights of the lines indicate how many of each ion was detected for this chemical using specific equipment and methods. Perfect matches usually require using the exact same equipment at the same settings, but there’s a lot of similarity when using equivalent machines.
Looking at the middle graph, where the two are compared against each other, you can see there’s a short line on our sample at 199 that doesn’t exist in the lower sample. And the relative heights of some of the key ions are different between the two. That doesn’t mean it’s not a match, but it isn’t a perfect match.
So Eddee checked and his lab did have a tiny bit of despropionyl-Fentanyl (aka 4-ANPP) left in their Fentanyl Analog Screening Kit (FAS Kit, sometimes referred to as a Traceable Opioid Material Kit, or TOM Kit).
There wasn’t much left, but he decided to try wet chemistry “derivitization” (a simple synthesis) using iodoethane, and was able to get a tiny amount of product he believes to be ethyl-despropionyl-fentanyl. He then ran that new product through a GC/MS and got the following output.
As above, in this image our unidentified substance is on the top; Eddee’s new ethyl-despropionyl-fentanyl is on the bottom.
Again, if one looks closely, there are some important differences between our sample (in blue on the top of the middle graph) and the newly synthesized chemical. There are several complexities we can’t completely account for. First, Eddee had only a teeny tiny amount of his synthesized chemical and sometimes “very low signal” amounts of a drug can have different Mass Spectrum profiles. Usually this doesn’t make a difference in which ions show up (except at the shortest peaks), but it can cause the relative ratios to be slightly different. Second, Eddee isn’t using the exact same GC/MS brand, model, and components as we have.
We might be able to change our GC coil and run parameters to better match this, but it’s so close, we’re going to consider this matter closed.
In an amusing postscript, one day after Eddee finalized this identification (Apr 4, 2022), DEA Special Testing and Research Laboratory (SFL1) wrote that they had come to the same identification of the so-called “308-G impurity”.
On July 12, Jurek from protestkit.eu, a Polish harm reduction and field reagent specialist, inquired about this sample, noting that the Ehrlich reagent photo showed an unexpected purple reaction. Jurek pointed out that 1P-LSD isn’t known to result in a purple color in the presence of Ehrlich reagent, helping to differentiate it from LSD-25, which does cause a purple color change with Ehrlich reagent.
We discussed this with our lab and learned that there was a small GC peak they had not initially reported in the results: inactive salts and inks on blotter do not always get reported due to DEA-imposed limitations.
Given the unexpected Ehrlich reaction, we published the spectrum for the unidentified chemical and added it to the results as a second chemical present in the sample.
A chemist in the Erowid Expert Network identified the unknown chemical as tryptamine, so we ordered a lab standard for tryptamine and found that it was a perfect match via GC/MS.
Further, DrugsData’s lab did side-by-side comparison in a ceramic well plate of lab standards for 1B-LSD, 1P-LSD, and LSD-25. The third of four wells is the ‘blank’ labeled MeCN (acetonitrile) which was the solvent used to dissolve each of the ergoloid standards (1B-LSD, 1P-LSD, LSD-25). Ehrlich reagent was applied to each, demonstrating that neither 1B-LSD nor 1P-LSD turn purple with Ehrlich, where LSD-25 does.
So the mystery of the the unexpected Ehlrich reaction for this 1P-LSD blotter is resolved, but the reason why someone added tryptamine to 1P-LSD blotter is still open. We all guess the goal was to be able to sell the 1P-LSD blotter as LSD-25, and that adding tryptamine to the 1P-LSD will result in reagent reactions consistent with LSD-25.
This is the first time Erowid has seen this type of adulteration of non-LSD ergoloids with the chemical tryptamine.
The image below is a link to a video of the reagent test:
Then, a photo of lab-grade tryptamine reacted with Ehrlich. A strong purple color:
Erowid’s DrugsData project recently tested two samples of 5-MeO-DMT that both contained an unidentified chemical. The first was dd10559, published Jun 08, 2021 and the second was dd10808, published July 19, 2021. Both samples were sold as 5-MeO-DMT and were reportedly sourced from the Netherlands to California. The unidentified chemical in the two samples appeared to be the same substance.
In June, one of our EEN experts (Eddee) proposed a possible identification for the chemical in the first sample, and we began consulting others in our network. Once we received the second sample, with apparently the same unidentified chemical, an outside expert weighed in with a slightly different proposed identification. We examined these more closely and with Eddee’s help, we think we’ve finalized our current opinion on the identity of the chemical dd10559-unid1 and dd10808-unid1:
This chemical is likely an unwanted byproduct resulting from imperfect synthesis of 5-MeO-DMT. Borax, one of Erowid’s main chemistry experts, proposed the name “N-methyl-Pinoline”, and Eddee proposed “N-methyl-5-Methoxytryptoline”.
Another expert pointed out that PubChem’s synonym list for this chemical includes 2-Methyl-6-methoxy-1,2,3,4-tetrahydro-beta-carboline (CAS# 6582-80-5), and cites the Japan Chemical Substance Dictionary for the CAS#. Isomer Design, a longtime supporter of the DrugsData project, refers to it as 6-MeO-2-Me-THβC.
We do not believe it has any common trivial name, and are currently settling on the name “N-methyl-Pinoline”. Its structure:
There were no published GC/MS graphs for this chemical. The identification is based on analysis of the fragmentation pattern, and on a 2020 paper, Synthesis and Characterization of 5‑MeO-DMT Succinate for Clinical Use, by Sherwood et al. Because of this paper, we originally considered calling this chemical “5-MeO-DMT Synthesis Byproduct A”, to parallel names given to unwanted synthesis products in other drugs.
The other proposed identification was the very similar compound 2,3,4,5-Tetrahydro-8-methoxy-2-methyl-1H-pyrido[4,3-b]indole (CAS# 41505-84-4).
The two proposed identified chemical structures have the same number of elements and chemical formula: C13 H16 N2 O ( C13H16N2O ). The only difference is which order the carbons are coming off the indole ring relative to the amine nitrogen.
This very technical image shows a comparison of the two chemicals, with our proposed ID in the upper panel and CAS 41505-84-4 in the bottom:
Now look again at the drawing of our identification and note the red line showing the bond between the indole ring and the methyl (carbon) coming off the nitrogen.
Finally, take a look at the structure of 5-MeO-DMT:
Imagine that the red line in the structure of N-methyl-Pinoline was broken where it connects to main rings. That substance, with that connection free, is 5-MeO-DMT. 5-MeO-DMT just happens to also have the same chemical formula: C13H18N2O.
Quoting from the Sherwood et al. 2020 paper: “Several small-scale attempts were initially evaluated with reaction monitoring by liquid chromatography-mass spectrometry (LCMS). Though product formation was evident, the reaction was plagued by challenges that would likely multiply at larger scales. The Pictet−Spengler reaction to the corresponding tryptoline (8) was difficult to suppress and removal of this structurally similar and possibly biologically active byproduct was challenging. Further optimization to Route 1 may be possible, but ultimately, the reaction was not recommended for further development.”
Their Scheme 1 Graphic shows what they label the “intractable byproduct”, which is the chemical we are proposing as the identification of the impurity in these two 5-MeO-DMT samples.
Thanks to everyone who participated in this: the submitter of the samples, Eddee, our anonymous experts, Borax, Sylvia, and the authors Sherwood AM, Claveau R, Lancelotta R, Kaylo KW, and Lenoch K for their excellent 2020 paper, which nailed down the reason for this unwanted contaminant in these synthetic 5-MeO-DMT samples.
Erowid’s DrugsData lab has recently changed from reporting simply “levamisole” to instead reporting “tetramisole/levamisole”. Tetramisole is the “real” primary name for this substance, a chemical that has two stereoisomers/enantiomers. For those unfamiliar, left (“lev”) and right (“dex”) isomers are only different in the same way that left- and right-handed gloves are different. They are also referred to as the “S-enantiomer” (lev) and the “R-enantiomer” (dex) of tetramisole. (Tetramisole refers to the “racemic” or mix of the S-enantiomer and R-enantiomer of the chemical.)
Many (though certainly not all) chemicals have this type of physical isomerism. An update in 2020 to the SWGDrug library that our lab uses as one of its sources changed the way it reports the name of the substance upon match. Neither the chief chemist at our lab nor any of our team remembers ever seeing the name “tetramisole” before December 2020. The technical distinction and update merits some further explanation.
The technical language can be pretty confusing. In some cases, the FDA allows commercial pharmaceuticals to use a shorthand, where they prepend “es” or “ar” (or “lev” and “dex”) to the front of a pharmaceutical name to denote an enantiomer-specific product. Examples include “armodafinil”, “eszopiclone”, and “escitalopram”.
Erowid’s DrugsData lab, using GC/MS testing, has no ability to isolate, separate, or identify which enantiomer is present, yet we’ve previously reported “levamisole” (the left or S-enantiomer) since first identifying this substance in cocaine samples in 2009 (see DrugsData Levamisole Results). Our lab’s techniques can’t distinguish the stereoisomer composition of any substance we analyze, e.g. a specific chemical identified in a single sample could be a 50/50 mix of R-enantiomer & S-enantiomer; 100% R-enantiomer and 0% S-enantiomer; 0% R-enantiomer and 100% S-enantiomer; or any ratio combination of the different physical isomers. This would be true for any lab using GC/MS for its testing process.
While DrugsData has been reporting “levamisole” since 2009, the question of enantiomers had not come up before. However, the “lev-” syllable should have been a giveaway. Sorry we didn’t identify this issue earlier!
In the last few years, research appears to indicate that most of the “levamisole” mixed with cocaine is actually the racemic tetramisole. In 2019, Madry et al. seemed to nail this issue down through analysis of hair samples from 627 cocaine users. The authors write: “Samples mainly contained racemic tetramisole (87.5%), only one sample contained levamisole only and two samples contained non-racemic [tetramisole].”
All of that, combined with our inability to test which spatial isomer we have in the samples we analyze, means that we’re going to switch to using “tetramisole” as the primary name for this substance, with “levamisole” being included so as to help avoid confusion due to the switch.
Reference:
Madry MM, Kraemer T, Baumgartner MR. “Cocaine adulteration with the anthelminthic tetramisole (levamisole/dexamisole): Long-term monitoring of its intake by chiral LC-MS/MS analysis of cocaine-positive hair samples”. Drug Test Anal. 2019 Mar;11(3):472-478. doi: 10.1002/dta.2505. Epub 2018 Oct 17. PMID: 30239147. Erowid Ref9448
Drug checking is a complex and evolving area of research. In EcstasyData’s effort to show accurate findings to the public, we’re working with the unique conditions of each sample. Most recently, the lab has innovated in its handling of LSD gel tabs.
There’s LSD, and then there’s gel tab LSD
Since 2014, the year EcstasyData’s lab developed its procedure for a practical and time-efficient way to identify LSD using GC/MS, gel tabs have been infrequently submitted for analysis. The majority of LSD samples submitted to our lab use blotter paper as the carrier (the lab requires that all samples be dry, no liquid samples are accepted without prior arrangement), though it is Erowid Center’s opinion that most of the LSD currently in distribution is in liquid/solution form.
Prior to 2017, the rare gel tab sample would get refused by the lab’s main chemist, who at the time did not feel confident that these samples could be adequately analyzed for the presence of LSD.
Besides analyzing each sample using GC/MS, which is the analytical method EcstasyData uses to detect the presence of chemicals, the lab also tests samples with reagents. Reagent testing adds descriptive data that adds to the collective knowledge base for drug checking. (Reagent testing can’t positively identify chemicals.)
It turns out that gelatin as a medium makes reagent testing more complicated; the pH conditions required to dissolve the gel affect the reagent even when dried. For this reason, gel tabs do not react normally to field reagents such as Marquis or Ehrlich.
De-weirding reagent colors
Between 2017 and November 2018, five gel tab samples were analyzed by EcstasyData, with GC/MS showing that four of them were LSD. The Ehrlich reagent reactions for these four samples were atypical. LSD normally reacts to Ehrlich reagent by turning purple, but when Ehrlich was applied directly to the dry (or even wet) gelatin in these cases, the results were mixed, turning brown or brown-purple, or other atypical reactions.
The lab began working with the special needs of these samples, and in November 2018, they developed a sample-preparation procedure that allows Ehrlich reagent to show a typical positive (rule-in) response to LSD in gel tabs.
New process for gelatin
We are publishing Erowid Center / DDL’s new procedure that is being used to process dry-gelatin-tab dose units, for the historical record, and so that others can duplicate it and critique it.
The following is the procedure that was used to produce the photo shown for Sample 6813, the first sample treated in this way:
Gel medium placed in small amount of water.
Basify gel-water mixture with NaOH.
Gel medium fully dissolves.
Solvent (ethyl acetate) added to gel-water mixture.
Solvent separated off and dropped onto ceramic well plate.
Unheated evaporation of solvent until dry.
Drop field reagents into wells, photograph.
This is the process that the lab will use to prep future gel tab samples for reagents. It will be interesting to see how other samples respond to it, and whether further tinkering with the process will be required.
As covered last week in Fentanyl Test Strips, Hot Spots, and Unhomogenized Samples, two samples reported in the November 6, 2017 batch of EcstasyData results were submitted to the lab with notes by the senders saying they had used fentanyl field tests on their sample before sending it.
The original GC/MS results for these samples (#5776 and #5779) did not reveal fentanyl. After writing about the problems associated with non-homogeneous samples and “hot spots”, we decided to use this as an opportunity to re-test both of these samples. This time, we used up 100% of what was sent by dissolving all of the sample (and not just a small portion), to make sure not to miss any potential “hot spots” in the original. That is a different method than our normal sampling protocol, meant to verify the no-fentanyl results.
On November 12, the lab reported back that the re-analysis of one of the samples returned a different result than the original analysis. The other sample’s result did not change.
Re-tested Using Modified Sample Prep Method
With most EcstasyData samples, there is material left over after an analysis. Whatever is not destroyed in the GC/MS process is stored for secure disposal after one year. This permits the lab to re-test a sample, potentially several times, if circumstances call for a re-test.
A modified method was used to re-test samples #5776 and #5779: For each of the re-tests, all the material, including the capsule, that was left over after the original analysis was placed in solvent to produce a consistent liquid sample, which was then run through the normal GC/MS process. This eliminated the “sub-sample of a sub-sample” condition that we described in the previous article.
Heroin Sample 5779: Positive fentanyl test-strip confirmed by GC/MS
The person who submitted the sample had noted the ‘Sample tested positive on both ‘DanceSafe’ and another brand of Fentanyl test strips (or cassette / dip card). Would like to know if these immunoassay fentanyl tests actually work.’ While the first GC/MS analysis did not detect fentanyl (even though a lot of the material was prepped for testing and the sample appeared homogenous), the second analysis that followed the method above did detect fentanyl.
This discrepancy in results can most likely be attributed to a hot spot or spots in the powder.
The lab also identified several other substances that they did not report in the first analysis: trace amounts of codeine, 4-ANPP, papaverine, and very small amounts of actylecodeine and 6-monoacetylmorphine. The additional very small findings are normal minor components of poorly-cleaned heroin produced from natural poppy resin. When we re-test a sample looking for very potent substances like fentanyl, we take a closer look at the trace and near-trace tiny “noise” bumps in the GC readouts.
Although we do report trace substances in most cases, street heroin is a good example of the type of material that often contains a lot of “noise” because it’s not pure, nor is it a combination of drugs; it’s a partially-synthesized natural product with lots of leftovers.
Because of the issue of fentanyl and fentanyl analogs showing up in heroin, EcstasyData has obtained a number of NPS-fentanyl analog standards and will be taking extra care to look for them in future heroin and opioid samples. Please include on your submission forms if you have concerns about fentanyl in your sample so the lab tech knows to look at what we normally consider “noise” in messy samples, and to set up the Gas Chromatograph run so that we make sure he can differentiate noise from signal at the time points where fentanyl and the known fentanyl analogs come out of the column.
The sample whose result did not change with re-analysis was for a powder represented as MDMA. Only MDMA, with no traces of fentanyl or other compounds, was detected using the method described above. The person who submitted the sample had noted a ‘strip test tested positive for Fentanyl’ prior to sending their sample in. This strip-test result was not confirmed by GC/MS.
Evolving and Improving Procedures
Although we run one of the best analytical projects of its kind in the world, this is a great example of the many types of errors and misses that can occur, and we take steps like those described here, to verify our results and change our procedures to improve the accuracy over time.
With fentanyl and fentanyl analogs haunting the opioid crisis in North America, some harm reduction field workers and users have been experimenting with what cost-effective reagent-based field tests might have to offer. One method that has been explored is the repurposed fentanyl urinalysis test-strip, where rather than dipping the test-strip in urine, it is dipped in a solution of the drug itself. A panel presentation covering the topic of drug checking and the opioid crisis was held at Drug Policy Alliance’s 2017 Reform Conference.
Since two samples included in the November 6, 2017 batch of EcstasyData results came with notes saying the sender had used a fentanyl test-strip on their sample before sending it, we’re starting to look at what that means for how we report EcstasyData results in such cases.
The question was posed by one sender, “Would like to know if these immunoassay fentanyl tests actually work.” Like many Yes/No questions that people have about drug analysis, the answer is a combination of “it depends” and “it’s complicated”.
Hot Spots
In answering the question, it helps to remember that not all powders will be completely evenly homogenized and may contain “hot spots” with uneven concentrations of a given chemical in sub-parts of the larger amount of powder or crushed crystalline material.
Powders and tablets that have more than one component to them aren’t always evenly mixed. Sometimes there’s a higher concentration of a drug in one or several areas. Think of a burrito that has hot salsa in one end of the burrito but not the other. If you bite into the burrito on one end, it’s spicy. On the other end, it’s not. Or a chocolate chip cookie — the chocolate chips might not be evenly distributed in the cookie. We’ve discussed homogenization in EcstasyData samples before when talking about traces of drugs in samples sent to the lab.
Hot spots are a bigger deal when it comes to fentanyl drugs or other similarly potent drugs, that are active at doses below a milligram but are sold in powders weighing hundreds of milligrams or grams.
Sub-samples of Sub-samples
When a powder sample is received by the EcstasyData lab, the lab tech preparing it for analysis first does a very simple partial homogenization by shaking the sample container or stirring it a little before extracting a sub-sample with a clean metal or plastic spoon. The sub-sample is then dissolved in a solvent and the technician confirms that the material dissolves completely or may take additional steps to get a fully dissolved, consistent liquid sample.
The dissolved sub-sample is then inserted into the testing equipment (the GC/MS). If fentanyl is present in that solution, then fentanyl will show up on the test, and we report it. If fentanyl is only present in a part of the sample that was not dissolved into solution, the fentanyl can not be detected.
So there are at least two steps of sub-sampling that occur before a tiny amount of material reaches the GC/MS:
1) The sender takes a sub-sample out of their stash/bag/jar at home and sends it to the lab.
2) The lab tech takes a sub-sample of that sub-sample to dissolve and inject into the GC/MS.
Someone using test-strips on powders or tablets at home is facing a similar issue of potential hot spots.
Can’t Be Sure
If a fentanyl test-strip is used to check a drug sample and the result is consistent with the presence of fentanyl (a so-called “positive”), there are several possible explanations, some including fentanyl being present, and some where there is not fentanyl present (“false positive”). A test-strip can also be difficult to read.
Some Positives are False Positives
A positive result with a test-strip can mean fentanyl is present in the sample, either deliberately, or by contamination. Tablets might have come into contact with the substance and have a tiny residue left that could trigger a positive field test.
An unknown and unknowable number of other conditions can cause false positives on urine drug screen strip-tests. Non-fentanyl drugs might trigger the field test to show positive. The problem of false positives is the reason urine strip-tests alone are insufficient to prove someone has taken a given drug in legal or employment contexts. Positives from urine screens are always double checked using an advanced technique such as GC/MS to confirm or exclude the simpler, cheaper strip test.
Test-Strip Outcome Can Be Hard to Interpret
Test-strips and other field tests often have a wide range of possible strengths of color changes. It is common to get results that are not 100% clear in what they mean.
EcstasyData can’t comment on whether fentanyl test-strips in general are useful in detecting fentanyl in drug samples. Each situation is unique.
PS: In August 2017, Erowid confirmed that the DanceSafe fentanyl test strips give false positives for buprenorphine. When mixed at a concentration of .01mg per ml water. We have another draft post that hasn’t seen proper review yet that goes over this in detail.
This last week, a sample was submitted and analyzed through EcstasyData that we clearly established was one of the three main ring-positional isomers of Methylethylcathinone (aka MEC). However, we didn’t have the lab standards on hand for this chemical, because it is the first time we’ve run into it since the supplier of lab standards we order from has stocked the three positional isomers.
Based on library matches* alone, it was impossible to be certain whether the sample contained 2-MEC, 3-MEC, or 4-MEC. We’ve run into this issue of positional isomers a bunch of times before over the last sixteen years of operating our street drug analysis project.
Luckily, Cayman Chemicals is a really great source of lab standards for NPS (“new psychoactive substances” aka psychoactive research chemicals). So we ordered reference standards for 2-MEC, 3-MEC, and 4-MEC, to find out if our equipment and lab procedures could make use of having the actual verified isomers on hand, for the purpose of confirming whether sample #5682 contained one or more of these slightly different versions of the same parent compound.
We ordered the standards on September 5th and they arrived at Drug Detection Laboratories (the lab that EcstasyData contracts with) on the 7th. The amazing DDL lab team, working on Saturday, ran the standards through their GC/MS and were able to confirm that sample #5682 contains only 4-Methylethylcathinone and none of the other two positional isomers. Yay!
There are many psychoactive chemicals with positional isomers that are difficult to reliably differentiate using GC/MS or UV absorption, even with the proper standards on hand. We’ve spent a lot of time over the last few years seeking clarity in our analysis of fluorinated amphetamines (2-, 3-, or 4-Fluoroamphetamine aka 4-FA) and the *-APB chemicals. And we’ve not been entirely successful. In most cases, one of the positional isomers is easy to tell apart from the others, but the other versions overlap in complex ways by retention time or fragmentation patterns. For MEC, the differences in column retention times for each of the positional isomers make them easy to differentiate using DDL’s Agilent GC/MS.
On another note, we also ordered a lab standard for Benzyl fentanyl this week, and were able to confirm that sample #5667 contains only Benzyl fentanyl. Less impressive, since we were pretty certain that’s what it was to begin with, but the initial match was based on comparing against other published spectra and not our own lab’s confirmation using a known standard of the same substance.
by Earth & Sylvia
Notes
*Identifying “by library match” refers to the process of comparing images of GC/MS output for a given sample to images of GC/MS output for a verified reference standard. Because equipment and lab procedures vary, to double-check identification by library match, a lab can acquire its own sample of a reference standard (if one is available), run it through the lab’s equipment, and compare the resulting images to those of the submitted sample being analyzed.
cassette / dip card