Researchers who study how drugs like morphine affect infants are bedeviled by the fact that newborns’ tiny bodies can’t readily spare much blood for testing. As a result, pharmacology in babies often involves guesswork. That could soon change.
A new method of screening miniscule amounts of dried blood for chemicals could allow researchers to get all the information they need from small amounts of blood. The researchers’ first goal is to produce a drug-dosing guide for infants. But the list of potential applications is far longer, says Jeffrey Galinkin, an anesthesiologist at the University of Colorado who heads the effort. Infection specialists could use the technique to diagnose HIV or tuberculosis, for instance, while sports officials could use it to monitor athletes for banned substances, he says.
The new approach relies on technology called liquid chromatography-mass spectrometry (LC-MS/MS), in which mass spectrometers use an electric charge to turn molecules into ions that can be identified and counted.
Recent design changes to increase the efficiency of ionization make modern LC-MS/MS devices up to 100 times more sensitive than older models, says Johnny Cardenas, a global marketing manager for the instrument maker AB Sciex. The test can be made even more sensitive by “cleaning up” the sample by using liquid chromatography—which sorts molecules by size, shape, or other parameters—before ionization.
When administering medications, doctors tend to treat kids as if they were simply small adults. That’s a perilous approach, says Gregory Hammer, an anesthesiologist at Stanford University who is collaborating on the National Institutes of Health-funded research. Hammer cites morphine as an example. In newborns, roughly 85 percent of body weight is water, compared with 60 to 70 percent for adults, he explains. Dosing the painkiller by body weight will produce a relative concentration that’s more dilute in a baby. The result: “We’ll underdose them,” Hammer says.
To examine the effects of morphine in babies now requires taking numerous blood samples from the infants, who only need the drug if they are hospitalized and critically ill. “We cannot draw very many samples” before jeopardizing their health, Hammer says. “But with dried blood spots, we can do as many samples as we want.”
Unlike liquid blood, dried spots on blotter paper do not require rigorous storage and handling, says Galinkin, who has formed a company, iC42 Integrated Solutions, to commercialize the work. Samples can be put in an envelope and dropped in a mailbox. That dramatically reduces the cost of shipping samples, he says, while giving clinics and public-health researchers in developing countries access to state-of-the-art laboratories anywhere in the world. Those labs could examine dried blood to measure the progression of diseases—and the effects of treatments—by analyzing biomarkers, molecular indicators of illness, in the blood.
The technique also could be used to screen athletes for performance-enhancing drugs. This would require only a single drop of blood taken under direct observation, avoiding the privacy issues involved with urine testing, notes Galinkin, who presented his group’s findings in October at the annual meeting of the American Society of Anesthesiologists. The researchers are now developing a panel to screen blood for between 100 and 200 drugs sanctioned by the World Anti-Doping Agency.
Olivier Rabin, the agency’s science director, says the ability to analyze dried blood with the mass spectrometer technology appears “very promising.” Rabin notes that testing blood is the only way to detect the use of human growth hormone, some newer agents to stimulate the production of red blood cells, gene doping, and other sophisticated methods of cheating. Although certain blood compounds must be measured in fresh blood, he says, “anything that can help us to gain in sensitivity and limit the volume of biological fluids is certainly of high interest to us.”