-
[show abstract]
[hide abstract]
ABSTRACT: The surge in interest in switching from traditionally used wet plasma to dried matrix spot (DMS) sampling and analysis to support pharmaceutical drug development is due to the significant ethical, financial and data quality advantages on offer. Unfortunately these advantages do not extend to sample bioanalysis, as DMS extraction is more complex than the protein precipitation method typically used for wet plasma analysis. Direct elution techniques coupled to HPLC-MS/MS have been identified as a potential means to counter this additional complexity.
The robustness and reproducibility of DMS HPLC-MS/MS data generated using a CAMAG DBS-MS 16 prototype automated direct elution instrument has been demonstrated to meet or exceed results obtained using a conventional manual extraction methodology.
The data generated suggest that a simple and fast direct elution method of DMS samples that does not require additional sample or extract clean-up, offers sufficiently robust performance to be compatible with high-sample-throughput quantitative analysis. Further evaluation of the technique and the development of more advanced fully automated direct elution instrumentation is fully warranted.
Bioanalysis 12/2011; 3(24):2769-81. · 3.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A novel technique is presented that addresses the issue of how to apply internal standard (IS) to dried matrix spot (DMS) samples that allows the IS to integrate with the sample prior to extraction. The TouchSpray, a piezo electric spray system, from The Technology Partnership (TTP), was used to apply methanol containing IS to dried blood spot (DBS) samples. It is demonstrated that this method of IS application has the potential to work in practice, for use in quantitative determination of circulating exposures of pharmaceuticals in toxicokinetic and pharmacokinetic studies. Three different methods of IS application were compared: addition of IS to control blood prior to DBS sample preparation (control 1), incorporation into extraction solvent (control 2), and the novel use of TouchSpray technology (test). It is demonstrated that there was no significant difference in accuracy and precision data using these three techniques obtained using both manual extraction and direct elution.
Analytical Chemistry 11/2011; 83(22):8779-86. · 5.86 Impact Factor
-
[show abstract]
[hide abstract]
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.
Journal of the American Society for Mass Spectrometry 09/2011; 22(9):1501-7. · 4.00 Impact Factor
-
Paul Abu-Rabie
Bioanalysis 08/2011; 3(15):1675-8. · 3.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A study was performed to evaluate the suitability of stored EDTA-treated control whole blood for use in the preparation of calibration standards and quality control samples for quantitative bioanalytical methods employing dried blood spot (DBS) samples to support pharmaceutical exposure studies.
It has been demonstrated that a storage time of 14 days for control human and animal blood is suitable for producing quantitative analytical results within internationally recognised acceptance criteria for two analytes. Furthermore, blood hemolysis and chill-thaw cycles have been evaluated and shown not to affect bioanalytical results notably. Aggressive mixing techniques can result in rat blood coagulation; however, this does not occur with other species tested and can be affected by the method of blood collection.
Control whole blood handled and stored using the recommendations generated from this study will not notably affect quantitative bioanalytical results when used for the preparation of calibration standards and quality control samples for DBS assays. It was demonstrated that control human and animal blood can be stored for periods long enough to effectively eliminate wastage.
Bioanalysis 08/2010; 2(8):1373-84. · 3.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The CAMAG thin-layer chromatography mass spectrometer (TLC-MS) interface has been assessed as a tool for the direct quantitative bioanalysis of drugs from dried blood spot (DBS) samples, using an MS detector, with or without high-performance liquid chromatography (HPLC) separation. The approach gave acceptable sensitivity, linearity, accuracy, and precision data for bioanalytical validations with and without the inclusion of HPLC separation. In addition, the direct elution technique was shown to increase assay sensitivity for a range of analytes representing a wide "chemical space" for pharmaceutical-type molecules over that obtained by conventional manual extraction of samples (punching of DBS and elution with solvent prior to HPLC-MS analysis). Investigations were performed to optimize extraction time, minimize sample-to-sample carry-over, and compare chromatographic performance. On the basis of this preliminary assessment, it has been demonstrated that the TLC-MS interface has the potential to be an effective tool for the direct analysis of drugs in DBS samples at physiologically relevant concentrations, an approach that could provide significant time and cost savings and greatly simplify bioanalytical procedures compared to current manual practices. Further, the increased sensitivity compared to that of manual extraction may enable the analysis of analytes not currently amenable to DBS sampling due to limitations in assay sensitivity.
Analytical Chemistry 11/2009; 81(24):10275-84. · 5.86 Impact Factor
