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Researchers Find Caffeine, Other Chemicals in Donor Blood Serum

In new research, Oregon State University scientists worked with biomedical suppliers to purchase and analyze 18 batches of human blood serum pooled from multiple donors (biomedical suppliers get their blood from blood banks, which pass along inventory that’s nearing its expiration date); the researchers found traces of caffeine in all 18 batches and also cough medicine and an anti-anxiety drug in many of the samples. The findings, published in the Journal of Pharmaceutical and Biomedical Analysis, point to the potential for contaminated blood transfusions, and also suggest that blood used in research isn’t necessarily pure.

Chen van Breemen found drugs in blood supply used for research. Image credit: Allinonemovie.

Chen van Breemen found drugs in blood supply used for research. Image credit: Allinonemovie.

“From a ‘contamination’ standpoint, caffeine is not a big worry for patients, though it may be a commentary on current society,” said Luying Chen, a Ph.D. student in the Linus Pauling Institute and the Department of Pharmaceutical Sciences at Oregon State University.

“But the other drugs being in there could be an issue for patients, as well as posing a problem for those of us doing this type of research because it’s hard to get clean blood samples.”

Chen and Oregon State University’s Professor Richard van Breemen tested pooled serum for alprazolam, an anti-anxiety medicine sold under the trade name Xanax; dextromethorphan, an over-the-counter cough suppressant; and tolbutamide, a medicine used to treat type 2 diabetes.

All of the pooled serum was free of tolbutamide, but eight samples contained dextromethorphan and 13 contained alprazolam — possibly meaning that if you ever need a blood transfusion, your odds of also receiving caffeine, cough medicine and an anti-anxiety drug are pretty good.

“The study leads you in that direction, though without doing a comprehensive survey of vendors and blood banks we can only speculate on how widespread the problem is,” Professor van Breemen said.

“Another thing to consider is that we found drugs that we just happened to be looking for in doing the drug interaction assay validation — how many others are in there too that we weren’t looking for?”

The goal of the study was to test a new method for evaluating the potential for interactions between botanical dietary supplements and drug metabolism.

The method involves rapid protein precipitation and ultra high pressure liquid chromatography and is being used to support clinical studies.

In the clinical studies, participants take a drug cocktail along with a botanical supplement — hops, licorice or red clover — to see if the supplement causes any of the drugs to be metabolized differently than they otherwise would.

“Botanicals basically contain natural products with drug-like activities,” Professor van Breemen said.

“Just as a drug may alter the drug-metabolizing enzymes, so can natural products.”

“It can become a real problem when someone takes a botanical supplement and is also on prescription drugs — how do those two interact? It’s not straightforward or necessarily predictable, thus the need for methods to look for these interactions. The odd thing in this case was finding all the tainted blood.”


Luying Chen Richard B. van Breemen. Validation of a sensitive UHPLC-MS/MS method for cytochrome P450 probe substrates caffeine, tolbutamide, dextromethorphan, and alprazolam in human serum reveals drug contamination of serum used for research. Journal of Pharmaceutical and Biomedical Analysis, published online November 10, 2019; doi: 10.1016/j.jpba.2019.112983

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