Dexamethasone quantification in dried blood spot samples using LC-MS: The potential for application to neonatal pharmacokinetic studies.

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dc.contributor.author Patel, Parul
dc.contributor.author Tanna, Sangeeta
dc.contributor.author Mulla, Hussain
dc.contributor.author Kairamkonda, V.
dc.contributor.author Pandya, Hitesh
dc.contributor.author Lawson, Graham
dc.date.accessioned 2010-11-25T12:25:22Z
dc.date.available 2010-11-25T12:25:22Z
dc.date.issued 2010
dc.identifier.citation Patel, P. et al. (2010) Dexamethasone quantification in dried blood spot samples using LC-MS: The potential for application to neonatal pharmacokinetic studies. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 878 (31), pp. 3277-3282 en
dc.identifier.issn 1570-0232
dc.identifier.uri http://hdl.handle.net/2086/4395
dc.description.abstract A high-performance liquid chromatography (LC-MS) method has been developed and validated for the determination of dexamethasone in dried blood spot (DBS) samples. For the preparation of DBS samples whole blood spiked with analyte was used to produce 30µl blood spots on specimen collection cards. An 8mm disc was cut from the dried blood spot and extracted using a combination of methanol: water (70:30, v/v) containing the internal standard, triamcinolone acetonide. Extracts were centrifuged and chromatographic separation was achieved using a Zorbax Eclipse Plus C18 column using gradient elution with a mobile phase of acetonitrile and water with formic acid at a flow rate of 0.2ml/min. LC-MS detection was conducted with single ion monitoring using target ions at m/z 393.1 for dexamethasone and 435.1 for the internal standard. The developed method was linear within the tested calibration range of 15-800ng/ml. The overall extraction recovery of dexamethasone from dried blood spot samples was 99.3% (94.3-105.7%). The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. Factors with potential to affect drug quantification measurements such as blood haematocrit, the volume of blood applied onto the collection card and spotting device were investigated. Although a haematocrit related effect was apparent, the assay accuracy and precision values remained within the 15% variability limit with fluctuations in haematocrit of ± 5%. Variations in the volume of blood spotted did not appear to affect the performance of the developed assay. Similar observations were made regarding the spotting device used. The methodology has been applied to determine levels of dexamethasone in DBS samples collected from a premature neonate. The measured concentrations were successfully evaluated using a simple 1 compartment pharmacokinetic model. Requiring only a microvolume (30µl) blood sample for analysis, the developed assay is particularly suited to pharmacokinetic studies involving paediatric populations. en
dc.language.iso en en
dc.publisher Elsevier en
dc.subject Dried blood spot (DBS) en
dc.subject LC-MS en
dc.subject Dexamethasone en
dc.subject chronic lung disease en
dc.subject Guthrie card en
dc.subject bioanalysis en
dc.title Dexamethasone quantification in dried blood spot samples using LC-MS: The potential for application to neonatal pharmacokinetic studies. en
dc.type Article en
dc.identifier.doi http://dx.doi.org/10.1016/j.jchromb.2010.10.009
dc.researchgroup Pharmacy Practice
dc.peerreviewed Yes en
dc.ref2014.selected 1365591152_10680145371_3_2


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