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Title: Methodological approaches to blood level quantification in neonates
Author: Teng, Meng
ISNI:       0000 0004 6059 4701
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
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The research presented in this thesis explored the development and utilisation of novel methodological approaches for the quantification of medicine levels in micro-samples from paediatric patients (primarily premature neonates). Three drugs / drug groups (gentamicin, beta-lactam antibiotics and caffeine) commonly used in neonates, and two sampling approaches, i.e. dried blood spot (DBS) sampling and microneedle (MN) array sampling were investigated. In the gentamicin study, the DBS sampling approach was coupled with ELISA determination of gentamicin concentrations. Having developed and validated the assay procedure, it was utilised to determine gentamicin concentrations in DBS samples collected from premature neonates who were prescribed gentamicin as part of their routine care.The work showed that plasma concentrations derived from DBS measurements correlated with plasma concentrations measured directly in a collaborating laboratory (using LC-MS/MS). PK parameters calculated using the DBS derived plasma values, and a basic one compartment PK model, yielded results within the expected range.A similar approach was used for the beta-lactams (amoxicillin, penicillin G and piperacillin) with blood in the form of DBS samples again being made available from paediatric patients who had been prescribed these agents. An LC-MS/MS method was used as the analytical platform.Furthermore, when patient DBS sample concentrations were converted to equivalent plasma concentrations they matched well (Bland-Altman test) with plasma samples.A completely novel approach to sampling was tested with caffeine. This work was carried out in healthy volunteers and involved the use of hydrogel forming MN patches. After ingesting caffeine, blood levels and ISF levels were measured using HPLC with UV detection. The MN approach was shown to provide semi-quantitative data for caffeine concentration vs time curves over the three hour post-dosing time frame This is the first demonstration of quantification of a drug using this MN approach within human subjects and provides a foundation for streamlining this methodology for future application in clinical settings.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available