Quantitative Analysis of Therapeutic Drugs in Dried Blood Spot Samples by Paper Spray Mass Spectrometry: An Avenue to Therapeutic Drug Monitoring |
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Authors: | Nicholas Edward Manicke Paul Abu-Rabie Neil Spooner Zheng Ouyang R Graham Cooks |
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Institution: | (1) Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA;(2) Drug Metabolism and Pharmacokinetics, GlaxoSmithKline Research and Development Ltd., Ware, UK;(3) School of Science, University of Greenwich, Medway Campus, Central Avenue, Kent, UK;(4) Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA;(5) Center for Analytical Instrumentation Development, Purdue University, West Lafayette, IN, USA; |
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Abstract: | A method is presented for the direct quantitative analysis of therapeutic drugs from dried blood spot samples by mass spectrometry.
The method, paper spray mass spectrometry, generates gas phase ions directly from the blood card paper used to store dried
blood samples without the need for complex sample preparation and separation; the entire time for preparation and analysis
of blood samples is around 30 s. Limits of detection were investigated for a chemically diverse set of some 15 therapeutic
drugs; hydrophobic and weakly basic drugs, such as sunitinib, citalopram, and verapamil, were found to be routinely detectable
at approximately 1 ng/mL. Samples were prepared by addition of the drug to whole blood. Drug concentrations were measured
quantitatively over several orders of magnitude, with accuracies within 10% of the expected value and relative standard deviation
(RSD) of around 10% by prespotting an internal standard solution onto the paper prior to application of the blood sample.
We have demonstrated that paper spray mass spectrometry can be used to quantitatively measure drug concentrations over the
entire therapeutic range for a wide variety of drugs. The high quality analytical data obtained indicate that the technique
may be a viable option for therapeutic drug monitoring. |
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