We describe and evaluate an alternative approach to pharmacokinetics based on ambient ionization mass spectrometry. Paper spray offers precise, accurate, and quantitative results which reduced consumables as well as sample analysis times (hours instead of days). This method utilized paper spray mass spectrometry, a technique in which a small volume of biofluid sample (in this case 10 �L blood) is added to a paper substrate that has been cut to a sharp point so as to produce a high electric field on application of a modest voltage. The biofluid remains largely trapped on the filter paper while soluble molecules are extracted on-line by a solvent, carried to the tip of the paper, and sprayed into the mass spectrometer in the form of highly-charged, micron-sized droplets. High-throughput analysis (50 seconds per sample) was performed using disposable paper spray cartridges and an automated source on an AB Sciex QTRAP 5500 mass spectrometer. Two commercial drugs, tamoxifen and olanzapine, were chosen for examination and results were validated using liquid chromatography mass spectrometry (LC/MS). The limits of detection for tamoxifen and olanzapine in whole blood by paper spray were 0.45 and 0.25 ng/mL, respectively. Using isotopically-labeled internal standards to normalize the analyte signal, the measured concentrations varied by 1 to 3% relative standard deviation (RSD) for the samples above the lower limit of quantitation. The slopes of the paper spray calibration curves using the automated source were stable (RSD 2.8%) over the course of two weeks. Pharmacokinetic data for tamoxifen from three rats by paper spray MS and LC/MS produced a Cmax of 42 and 43 ng/mL, respectively, and areas under the curve of 414 and 449 hours�ng/mL, respectively.

Pharmacokinetics using paper: An alternative to LC/MS

247th National Meeting (2014)

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