Browsing by Author "Mulla, Hussain"
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Item Metadata only Analysis of dried blood spots - The potential for paediatric pharmakokinetic studies of captopril.(2010-07-26) Tanna, Sangeeta; Mulla, Hussain; Pandya, Hitesh; Titman, C.; Lawson, GrahamItem Metadata only Applying dried blood spot analysis: the pathway to better paediatric care.(Pharmaceutical Press, 2009) Patel, Parul; Lawson, Graham; Mulla, Hussain; Tanna, SangeetaItem Metadata only Assessment of liquid captopril formulations used in children.(BMJ Publishing, 2010) Mulla, Hussain; Hussain, N.; Tanna, Sangeeta; Lawson, Graham; Manktelow, B. N.; Tuleu, C.; Samani, N. J.; Pandya, HiteshItem Metadata only Captopril Determination in Dried Blood Spot Samples with LC-MS and LCHRMS: A Potential Method for Neonate Pharmacokinetic Studies(OMICS Publishing Group, 2012-03-07) Lawson, Graham; Mulla, Hussain; Tanna, SangeetaThe use of blood spot collection cards was investigated as a means of obtaining small volume samples for the analysis of therapeutic drugs for the purpose of neonatal pharmacokinetic studies. We describe the development of two micro-analytical methods for the determination of captopril extracted from dried blood spots (DBS). Firstly a liquid chromatography ion-trap mass spectrometry method with selected ion monitoring (LC-MS(SIM)) of target ion at m/z 218.0 was developed to determine captopril levels in 8mm discs punched from each DBS. This was compared in terms of specificity and sensitivity to a simple accurate mass liquid chromatography high resolution TOF mass spectrometry (LC-HRMS) method in which MS detection was carried out in electrospray positive ion mode for target ions at m/z 218.0845 for captopril and 377.2084 for the IS. Dithiothreitol was used both to pre-treat the sampling cards and as part of the extraction medium in order to stabilise the DBS extracted captopril. Drug extraction efficiency from spiked blood spots was demonstrated to be 90 ± 10% and the drug was stable in DBS for at least 12 weeks. Validation of both micro-analytical methods showed good precision and accuracy and the LC-HRMS method was linear within the tested calibration range 10-400ng/ml for captopril and had improved sensitivity and specificity compared to the LC-MS(SIM) method. This method was applied to blood spots on sampling card from a neonate patient previously administered 1mg/kg captopril orally. The amount of captopril in the DBS was 88ng/ml. Requiring only a micro volume (30µl) blood sample for analysis, the developed DBS based micro-analytical method has the potential to facilitate pharmacokinetic studies of captopril in children.Item Metadata only Dexamethasone quantification in dried blood spot samples using LC-MS: The potential for application to neonatal pharmacokinetic studies.(Elsevier, 2010) Patel, Parul; Tanna, Sangeeta; Mulla, Hussain; Kairamkonda, V.; Pandya, Hitesh; Lawson, GrahamA 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.Item Metadata only Dried blood spot analysis - a comparison of SIM, MSMS and accurate mass ToF analyses for selected drugs.(2010-11-27) Tanna, Sangeeta; Patel, P.; Mulla, Hussain; Lawson, GrahamItem Metadata only Dried blood spot analysis to improve paediatric medication.(Separation Science Asia Meeting Singapore. 2011, 2011-07-27) Tanna, Sangeeta; Patel, P.; Mulla, Hussain; Lawson, GrahamItem Open Access Dried blood spot sampling with LC-MS analysis for routine therapeutic caffeine monitoring in neonates(International Scholarly Research Network, 2012-11) Lawson, Graham; Patel, Parul; Mulla, Hussain; Tanna, SangeetaA liquid chromatography–mass spectrometry (LC-MS) method was developed and validated for the determination of therapeutic levels of caffeine in dried blood spot (DBS) samples. Caffeine is used in the treatment of Apnoea of Prematurity (AoP) in newborn children. Calibration DBS samples were prepared by spotting 15l of whole blood spiked with the analyte onto specimen collection cards. 5mm disks cut from the centre of the DBS were extracted in methanol containing the internal standard. The extract was separated using a Zorbax Eclipse Plus C18 column and the MS, operated in electrospray positive ion mode, used single ion monitoring at m/z 195 for caffeine and 198 for the IS. The overall extraction recovery of caffeine from spiked blood spots was demonstrated to be 44-47%. Validation of the micro-analytical method showed good precision (coefficient of variation) and accuracy (relative error) and specificity and was linear within the tested calibration range 500-25000ng/ml for caffeine. Investigation of different specimen collection papers revealed different matrix effects with significant ion suppression from the FTA Elute paper itself. Requiring only a micro volume (15µl) blood sample for analysis, the developed DBS based micro-analytical method has the potential to facilitate the routine monitoring of caffeine in neonates.Item Metadata only Dried blood spots and sparse sampling: A practical approach to estimating pharmacokinetic parameters of caffeine in preterm infants(Wiley, 2013) Patel, Parul; Mulla, Hussain; Kairamkonda, V.; Spooner, N.; Gade, S.; Della Pasqua, O.; Field, D. J.; Pandya, HiteshItem Metadata only Drug disposition during Extra Corporeal Membrane Oxygenation ECMO(Informa Healthcare, 2001) Lawson, Graham; Mulla, Hussain; Upton, D. R.; Firmin, RichardItem Open Access Examples of dried blood spot sampling and analysis to improve paediatric medicine(2011-06) Lawson, Graham; Mulla, Hussain; Patel, Parul; Tanna, SangeetaItem Metadata only Facilitating paediatric PK studies: Utility of the dried blood spot technique(2009) Patel, Parul; Mulla, Hussain; Pandya, Hitesh; Lawson, Graham; Tanna, SangeetaItem Metadata only Facilitating pharmacokinetic studies in children: a new use of dried blood spots.(BMJ Publishing, 2010) Mulla, Hussain; Tanna, Sangeeta; Pandya, Hitesh; Patel, ParulItem Metadata only From laboratory to bedside and back again - The use of blood spot analysis in paediatric care(2009) Tanna, Sangeeta; Mulla, Hussain; Pandya, Hitesh; Lawson, GrahamItem Metadata only From laboratory to bedside and back again: the use of dried blood spot analysis in paediatric care.(Pharmaceutical Press, 2009) Lawson, Graham; Tanna, Sangeeta; Mulla, Hussain; Pandya, HiteshItem Open Access An investigation into the effects of extracorporeal membrane oxygenation on pharmacokinetics(De Montfort University, 2003) Mulla, HussainItem Metadata only Personalised dosing of medicines for children(Wiley, 2017-03-07) Al-Metwali, Basma; Mulla, HussainItem Open Access Personalised warfarin dosing in children post cardiac surgery(Springer, 2019-10-05) Goodyer, Larry; Rivers, Peter; O'Hare, Linda; Young, Sanfui; Mulla, Hussain; Metwali, B.Warfarin dosing is challenging due to a multitude of factors affecting its pharmacokinetics (PK) and pharmacodynamics (PD). A novel personalised dosing algorithm predicated on a warfarin PK/PD model and incorporating CYP2C9 and VKORC1 genotype information has been developed for children. The present prospective, observational study aimed to compare the model with conventional weight-based dosing. The study involved 2 groups of children post cardiac surgery: Group 1 were warfarin naïve, in whom loading and maintenance doses were estimated using the model over a 6-month duration and compared to historical case matched controls. Group 2 were already established on maintenance therapy and randomised into a cross-over study comparing the model with conventional maintenance dosing, over a 12-month period. Five patients enrolled in Group 1. Compared to the control group, the median time to achieve the first therapeutic INR was longer (5 vs 2 days), to stable anticoagulation was shorter (29.0 vs 96.5 days), to over-anticoagulation was longer (15.0 vs 4.0 days). Also, median percentage of INRs within the target range (%ITR) and percentage of time in therapeutic range (%TTR) was higher; 70% vs 47.4% and 83.4% vs 62.3%, respectively. Group 2 included 26 patients. No significant differences in INR control were found between model and conventional dosing phases; mean %ITR was 68.82% versus 67.9% (p=0.84) and mean %TTR was 85.47% versus 80.2% (p=0.09), respectively. The results suggest model-based dosing can improve anticoagulation control, particularly when initiating and stabilising warfarin dosing. Larger studies are needed to confirm these findings.Item Metadata only Pharmacokinetics of Midazolam in neonates undergoing extracorporeal membrane oxygenation(Lippincott, 2003) Lawson, Graham; McCormack, P.; Mulla, Hussain; Firmin, L.; Upton, D. R.Item Metadata only Plasma concentrations of midazolam in neonates receiving extracorporeal membrane oxygenation(Lippincott, 2003) Lawson, Graham; Mulla, Hussain; Firmin, L.; Upton, D. R.; Peek, G.