Staying ahead of a growing menace
They have names like Spice, K2, Black Mamba, Cloud Nine, Maui Wowie, Mr. Nice Guy, 251 NBOMe, and bath salts. They are synthetic cannabinoids, hallucinogens, and cathinones, and they are keeping law enforcement -- and forensic laboratories -- very busy.

While their users seek a legal high, "designer drugs" impose serious costs on society, adding burdens to healthcare and law enforcement and adversely affecting the health of users from kidney injury, psychosis, seizures, coma, and even death. Their underground purveyors stay one step ahead of the law by continuously reformulating their products to evade prosecution. The result is a nonstop game of cat and mouse.

"There are two new designer drugs coming into the market every week and our task is to develop and validate a method for analyzing them," said Petur Dalsgaard. As a forensic scientist in the Section of Forensic Chemistry at the University of Copenhagen, he is on the front lines of the battle against designer drugs.

"Our primary role is to be a service to the police and to the pathologists," Dalsgaard explained. "They come to us with different samples -- blood samples, urine samples, hair samples -- and it’s our job to find out what drugs are in these samples."

Dalsgaard and his colleagues have published 15 articles detailing their methods since 2004.

The challenge: faster, better, more affordable
"We have to work efficiently and keep costs down," he noted. "And time is always a factor. We work as fast as we can but it can sometimes take weeks for results to be obtained, confirmed and properly interpreted."

On top of all that, the results need to be able to stand up in court. To meet these needs, Dalsgaard has developed particular expertise in LC/MS. His laboratory includes two Xevo G2-S Q-ToF systems controlled by UNIFI software, two Xevo TQ-S, and two ACQUITY TQD tandem quadrupole systems.

"We are unique among laboratories in that we are using LC/MS for a lot of analysis," he noted.

"We use the triple quadrupole mass spectrometers for quantification," he explained. "Combined with UPLC, you can get really short chromatography runs, and with MRM scanning, an analysis can take only a few minutes for each injection. Our time-of-flight mass spectrometers are running in parallel with the triple quadrupole instruments, so we’re able to do quantification and confirmation at the same time. Time-of-flight instruments are really good at screening for unknown compounds for which reference standards and spectra don’t yet exist."

Software increases throughput
Dalsgaard has seen the pace and accuracy of analysis increase steadily, thanks in large part to software improvements.

"There is a world of difference between what we could do when I first entered this field and what we can now," said Dalsgaard. "Today, we can screen for 3,000 compounds in a single analysis.  And the technology is getting better all the time."

Dalsgaard also credits new techniques, such as Waters' MS^E, and UNIFI software.

"The time-of-flight instruments will collect everything, and with this MS^E technology, you get a fragmentation of everything as well," he said. "And if you get sophisticated software, too, like UNIFI, then you can really do a lot of work.  You can have big libraries running, so you can screen for thousands of drugs at the same time. Every time we find a drug that the triple quadrupoles don’t pick up, then we run an additional analysis where we quantify this drug."

"On the sample preparation side, we’ve also done a lot of development," Dalsgaard pointed out. "When I started here nine years ago, sample preparation was done manually. Today sample preparation is largely automated. We can also obtain more information from smaller amounts of sample with less difficulty and with more precision."

Dalsgaard expects throughput to continue to rise as new technologies, such as ion mobility, become more widely available.

"What’s going to be really interesting is the new dimension provided by ion mobility," he noted. "Once people start building libraries with these CCS values, then we will see it really start to take off and then you can also have a very accurate hit while still screening for thousands of compounds."

A remote island boyhood
Doing drug analysis for the police in busy Copenhagen seems a world away from the Faroe Islands, where Dalsgaard grew up. Located in a remote area of the north Atlantic Ocean about halfway between Norway and Iceland, the cluster of rocky islands has a population of only 50,000 people. It was there that Dalsgaard, the son of an architect and a business school teacher, developed an interest in science.

"I was working in a local pharmacy and was told the job security was good," he explained. "So, I applied to go to pharmacy school to be a master of pharmacy."

As Dalsgaard's studies continued, he found himself getting further drawn into analytical science. His Master’s thesis was devoted to seeking anti-HIV and anti-cancer drugs from natural products. That led to a PhD in Natural Products Chemistry earned from the University of Copenhagen and the Technical University of Denmark.

It was at the Technical University of Denmark that he was introduced to LC/MS and time-of-flight instruments. After completing his PhD, he worked in Switzerland in natural products chemistry, before the position in the Forensic Section at the University of Copenhagen opened up.

Filling the downtime with family and music
The nonstop pace of work and the discovery of new compounds keep Dalsgaard engaged and driven. In his off-hours, he spends time with his three children -- ages 3, 6, and 9 -- and plays the drums in a classic rock band with other scientists.

"A month ago, I played a concert in the Faroe Islands, where 500 people bought a ticket to hear the band play," he said. "It's a strange thing to be attending a scientific conference in the US one day and the next day you're playing a small club in a totally different part of the world."

Playing music provides a break from the nonstop work of the laboratory, a quest he clearly relishes.

"I get excited when we find a new designer drug for the first time in a blood sample," said Dalsgaard. "I really love coming in in the morning and taking a look at the data we recorded the previous night, and having a look at all the traces to see what the instruments found in the sample."