A simple bioanalytical method for the quantification of antiepileptic drugs in dried blood spots

An increasing number of publications on the dried blood spot (DBS) sampling approach for the quantification of drugs and metabolites have been spurred on by the inherent advantages of this sampling technique. In the present research, a selective and sensitive high-performance liquid chromatography method for the concurrent determination of multiple antiepileptic drugs (AEDs) [levetiracetam (LVT), lamotrigine (LTG), phenobarbital (PHB)], carbamazepine (CBZ) and its active metabolite carbamazepine-10,11 epoxide (CBZE)] in a single DBS has been developed and validated. Whole blood was spotted onto Guthrie cards and dried. Using a standard punch (6 mm diameter), a circular disc was punched from the card and extracted with methanol: acetonitrile (3:1, v/v) containing hexobarbital (Internal Standard) and sonicated prior to evaporation. The extract was then dissolved in water and vortex mixed before undergoing solid phase extraction using HLB cartridges. Chromatographic separation of the AEDs was achieved using Waters XBridge™ C18 column with a gradient system. The developed method was linear over the concentration ranges studied with r ≥ 0.995 for all compounds. The lower limits of quantification (LLOQs) were 2, 1, 2, 0.5 and 1 μg/mL for LVT, LTG, PHB, CBZE and CBZ, respectively. Accuracy (%RE) and precision (%CV) values for within and between day were <20% at the LLOQs and <15% at all other concentrations tested. This method was successfully applied to the analysis of the AEDs in DBS samples taken from children with epilepsy for the assessment of their adherence to prescribed treatments.

Internal market orientation:construct, measurement and consequences

This thesis contributes to the paucity of marketing research into the area of internal marketing. Drawing from knowledge developed in a diverse range of marketing and management literatures, the domaill of internal marketing is clarified Gild a new concept, internal market orientation is developed. A new instrument, measuring the internal market orientation, is developed and subjected to standard scale development procedures. Six dimensions of the construct are confirmed; collegial interaction, group interaction, jorlllal interaction, external envirollment, wage flexibility and job flexibility. A sample of 766 UK retail store managers are surveyed to identify levels of internal market orientation and external market orientation in large UK multi-product, multi-site retailers and the structural relationships between internal market orientation, extemal market orientation alld company performance are examined. The external market orientation construct is applied to the local retail market and established measurement instruments adapted to this pwpose. Three measures of performance are employed ill this study. The structural relationships between the six dimensions of internal market orientation and the three dimensions of external market orientation are examined employing structural equations methodology, using LISREL 8.3. alld the impact of internal market orientation Oil external market orientation and company performance is measured. The study finds no direct link between internal market orientation and financial performance but does identify the moderated role of internal market orientation on financial performance. Significant relationships between three of the six dimensions of internal market orientation and the three dimensions of external market orientation are identified and the impact of internal market orientation on the retention of employees and their behaviour is also identified. The research findings contribute to marketing theory by providing empirical evidence to support the long held assumption that internal marketing has an impact on marketing success and offers an explanation of the mechanism by which this influence operates. For marketing practitioners, the research findings offer additional information on which services marketing strategies may be formulated.