Health

How Drug Forensics Work to Solve Overdose Mysteries

A series of overdoses in Georgia highlights how scientists identify the drug cocktails at the heart of America's deepening opioid epidemic.

Authorities in Georgia have a chemical whodunit on their hands as they try to figure out what’s in a batch of lethal yellow pills.

The pills were marked as Percocet, a widely prescribed opioid painkiller that’s popular among addicts. But they contained a drug cocktail that’s believed to have killed four people and put more than two dozen others in hospitals across south-central Georgia, according to the state Department of Public Health.

Scientific detective work already has tentatively identified two drugs in the tablets. One of them is a previously unknown analogue of the powerful synthetic opioid fentanyl, which has been linked to hundreds of deaths in Georgia and thousands nationwide, the Georgia Bureau of Investigation reported Thursday.

“When it came back, right away they said they hadn’t seen it before,” said Nelly Miles, a spokeswoman for the agency. The second is a previously identified drug that is being kept under wraps while testing continues, Miles said.

The chemistry of the victims’ blood and samples of the pills themselves will likely produce more clues, said Peter Stout, a toxicologist and CEO of the Houston Forensic Science Center in Texas.

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There are no good tests for fentanyl that can be administered in an emergency room, Stout said. But fentanyl and other drugs will show up readily when a sample is analyzed with high-tech tools.

Mass spectrometry and liquid or gas chromatography can break down the contents of a blood sample into their component compounds, separating them out by boiling points or molecular weights. Gas chromatography is commonly used for drug samples, he said.

“We take a little bit of the pill, dissolve it in a solvent, run it in the gas chromatograph mass spectrometer and compare that spectrum and retention time to a known standard,” he said.

A compound like fentanyl will show up on a readout in a particular pattern. But when something the lab technicians haven’t seen before pops up, “it can be a real problem,” Stout said.

“We start looking toward networks of our colleagues and asking other laboratories, both here in the States and abroad, ‘Have you seen a spectrum that looks like this?’ ” he said. Private companies, chemistry societies, and the federal Drug Enforcement Administration will collect readouts of “the new and bizarre” and distribute them to labs. But a new variation on a drug might take anywhere from days to months to identify, depending on whether another lab has already seen the substance and how long it takes to connect with them.

Blood samples from a drug user can also help identify a substance. When drugs break down in the body, they form compounds known as metabolites that can point back to the original substance.

But the tiny amounts of those compounds can be harder to analyze than seized samples of the drug itself, Stout said. Fentanyl often is administered in millionths of a gram — and the chemical traces it leaves behind measure in the trillionths of a gram.

“In the landscape of new psychoactives, it’s not terribly common that we run up on something that somebody hasn’t seen the parent drug,” Stout said. And when dealing with the tiny amounts found in blood samples, “Now you’re starting to guess at common metabolic pathways … and there’s only so much you can guess at.”

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Miles said the GBI’s chemists used some of those same techniques to identify the drugs at the heart of Georgia’s mystery, and they’re waiting for records from a chemical company to compare with the previously unknown fentanyl variant.

“These additional steps definitely are representing obstacles to us,” she said. But she said the results, once confirmed, may help explain some of the unusual symptoms seen in the Georgia cases — and the numbers may rise as doctors get a better idea of what to look for.

“There were some similarities to your typical opioid overdose … but there were additional factors like respiratory depression,” Miles said. Some of the patients have had to be put on ventilators to help them breathe, and some were still on ventilators Thursday night, she said.

Opioid overdose deaths in the United States have tripled since 2000 as painkillers like oxycodone, hydrocodone, and fentanyl became more widely prescribed. Fentanyl in particular can be up to 100 times more powerful than morphine, and Georgia saw about 250 fentanyl-related deaths in 2015.

The state has responded to its opioid problem in part by allowing over-the-counter access to nalaxone, a drug that can rapidly reverse 

In late May, the GBI issued a warning about a new batch of counterfeit pills that were marked as oxycodone — the drug that also provides the kick behind Percocet — but which also contained fentanyl and its offshoots, which can be absorbed through the skin.

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