Some postmortem toxicology for a snowy Monday: When Heroin isn't Heroin.
Heroin - diacetylmorphine, from the acetylation of morphine, via the opium poppy - is rapidly metabolized to 6-acetylmorphine (6AM) and morphine. We also see a bit of codeine and other opiate alkaloids.
Heroin - diacetylmorphine, from the acetylation of morphine, via the opium poppy - is rapidly metabolized to 6-acetylmorphine (6AM) and morphine. We also see a bit of codeine and other opiate alkaloids.
So we'll screen postmortem central blood, like from the aorta or IVC, and usually find morphine, a bit of codeine, and a bit of 6-AM. We'll confirm on a peripheral blood specimen, like femoral or iliac, and find morphine, a bit of codeine, and 6AM. Pretty routine stuff.
If we can't confirm the 6AM in blood, we can always look at the urine, which is a great specimen for this, but another good one is the vitreous humor. That's the fluid in your eye. Yes, we can detect drugs in there, too. It's an underutilized specimen for dug toxicology, IMO.
If we don't find any codeine, that's OK, it's coming naturally from the opium poppy, and ratios of morphine to codeine vary, but it's in the 10:1, 20:1, range. It's the morphine and the presence of 6AM that screams HEROIN. This is correct 99.999% of the time.
So what's that 0.001% when we find morphine and 6AM and it's not heroin, you ask? That would be the really rare instance, literally about 1 in 10,000 heroin cases, where there is in vivo production of 6AM. Yes, in vivo production, no heroin required!
A bit of background first. Our usual heroin cases are stereotypically young, white, males. They're often known drug users, with paraphernalia around them, sometimes with a needle still in their arm. Can they be old? Sure. We've all seen 70-year-old heroin users.
In our stereotypical case we see morphine, codeine, and 6AM. Sometimes no codeine, but again, it's the 6AM that really nails it, But once every 3 years or so we get a case where we see morphine and 6AM. No codeine. But not surprising though, like what I said a few tweets back.
The history may be an individual prescribed morphine. Not a known illicit drug user. No paraphernalia. Nothing that screams out "drug user." So what gives? The perfect storm of morphine + aspirin = 6AM, that's what.
Aspirin, acetylsalicylic acid, can acetylate morphine in vivo to produce acetylmorphine, preferentially 3-acetylmorphine. Most laboratories don't separate the 3AM and 6AM isomers because the 6AM isomer dominates in heroin cases.
The key in these cases is the lack of codeine - which I told you before isn't always important, until it is. In moderate morphine concentrations, I'd *expect* to see some codeine, maybe 10% that of the morphine. So if have a 100 ng/mL morphine, I'm expecting a 10 ng/mL codeine.
Knowing my assay's limit of detection, if I don't see any codeine at all when I expect to, then something is up. That's where the death investigation work is important. The history surrounding the case. The decedent's prescription history.
I may run the urine and vitreous humor to check for codeine, but it's not appreciably there either. Oh yeah, codeine is an impurity in prescription morphine formulations, usually around 0.1% or so, so be wary of that if you see a *tiny, tiny* bit in the urine.
So we'll check for salicylates, from aspirin, and there it is! Family may also state they take daily aspirin. The forensic pathologist doesn't see evidence of an opioid overdose either. No pulmonary edema, no early pneumonia, no foam in airways, etc. All the pieces fit together.
Why does all of this matter? It's the difference between the cause of death being HEROIN versus something else, drug overdose or otherwise. Maybe they did die of a morphine overdose, but there's still a stigma around heroin.
Do you want heroin on your grandmother's death certificate? Probably not. It could also play a role in issuing death benefits. But the real reason it matters is that our job is to get it right. Our goal is 100% of the time. Anything less, and we've failed.
Again, super rare. I've seen it twice in nearly 10 years and 25,000+ drug OD cases. This also highlights experience being important in forensics - it takes time to see everything. For more reading here's a paper on the phenomenon: academic.oup.com/jat/article/37…
