It’s in a drop of blood – or is it?

Date

2016-03-07

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Presentation

Peer reviewed

Abstract

Introduction: Over 355 million prescriptions were dispensed for heart diseases in the UK in 2013. Half of these, costing the NHS £2.3 billion, were wasted because patients did not take their medicines as prescribed [1]. Evidence suggests that about 50% of cardiovascular patients do not adhere to treatment. This results in poor health, high cost of care and in some cases death [2]. Current methods of assessing adherence to medication mainly involve self-report, pill counts and electronic monitors which only assume ingestion. The invasive collection of 1-10mls of blood for therapeutic drug monitoring is common, but this research focuses on the use of a dried blood spots (DBS) collected from a simple finger prick. The DBS samples were used to assess adherence to 8 commonly prescribed cardiovascular drugs to optimize treatment for patients. Methods: Dried blood spot (DBS) sample collection followed by liquid chromatography-time of flight mass spectrometry (LC-ToF MS) analyses[3,4] was developed and validated for quantification of 8 commonly UK prescribed heart medicines: atenolol, bisoprolol, diltiazem, doxazosin, losartan, ramipril, simvastatin and valsartan. For the preparation of DBS calibration samples whole blood was spiked with 8 target analytes to produce 30µl blood spots on specimen cards. 8mm disc was punched out and extracted with methanol containing the internal standard, atenolol D7. Chromatography analysis was performed using gradient elution with a run time of 2.5 min. Identification was carried out using electrospray ionisation (positive) in conjunction with high resolution (ToF) MS detection. The developed bioanalytical method was applied to blood spot samples taken from adult volunteers previously administered one or more of the target drugs. Results: The bioanalytical method validation showed good linearity and the accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all tested concentrations for the 8 target drugs. Drug recoveries from spiked blood spots were ≥ 82% for atenolol, bisoprolol, diltiazem, doxazosin, losartan, ramipril and valsartan. The method is highly sensitive, with Limit of Quantification (LOQ) at 10ng/ml for atenolol, 0.5ng/ml for atorvastatin, 0.1ng/ml for bisoprolol, 0.5ng/ml for diltiazem, 0.1ng/ml for doxazosin, 0.1ng/ml for lisinopril, 0.5ng/ml for losartan, 0.1ng/ml for ramipril, 0.1ng/ml for simvastatin and 50ng/ml for valsartan. Results from DBS samples taken from 22 volunteers prescribed with one or more of the cardiovascular drugs were within expected levels with respect to published pharmacokinetic data. Conclusions: The developed method has the potential to both assess medication adherence and to allow re-interrogation of data collected for heart disease patients. This method has potential to save the NHS money in wasted medicines and will allow health practitioners to personalize and optimize drug treatments for their patients.

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Keywords

Microsampling, Cardiovascular drugs, Dried blood spot (DBS), Liquid chromatography-high resolution mass spectrometry (LC-HRMS), Medication adherence, Therapeutic drug monitoring (TDM)

Citation

Bernieh, D., Lawson, G. and Tanna, S. (2016) It’s in a drop of blood – or is it? SET for Britain (Science, Engineering and Technology ), House of Commons, London, March 2016.

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Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)