Performance of two different microsamplers for the LC-HRMS analysis of 10 cardiovascular drugs




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Peer reviewed



Introduction: Evidence suggests that ˃50% of heart disease patients do not adhere to treatment. This means half of the 370 million prescriptions dispensed for cardiovascular diseases (CVD) in the UK yearly, are wasted [1]. Wasted (unused) medicines cost the NHS up to £4 billion annually. Treatment success is also affected by variations in individual drug metabolism, drug-drug interactions and selecting appropriate dosage. Dried matrix microsampling combined with LC-HRMS detection has the potential to offer an objective means of assessing medication adherence [1, 2] to enable clinicians to optimise and personalise treatment for patients. However challenges in using DBS hampers the attractiveness of this technique. Novel microsamplers have been developed to overcome the limitations with DBS cards when a sub punch is used. This work compares the performance of the novel volumetric absorptive microsampling (VAMS) device and the traditional DBS card in terms of quantification for 11 cardiovascular drugs in a medication adherence study. Method: Chromatographic analyses were performed on a Zorbax column using gradient elution with a run time of 2.5 min. Identification was carried out using electrospray ionisation (positive) on an Agilent 6530A QTOF mass spectrometer. For the preparation of DBS calibration samples whole blood was spiked with the 11 target analytes to produce 30µl blood spots on specimen cards and dried. 8mm discs were punched out from DBS cards and the whole substrate was used for VAMs. Spots were extracted with methanol containing the internal standard. The developed and validated bioanalytical method was applied to finger prick blood samples taken from adult patients previously administered one or more of the target drugs. Results: The method validation showed good linearity. The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all tested concentrations for the 11 target drugs on both sampling devices. Haematocrit effect were significant on DBS card, but not on the VAMs device. Drug recoveries from spiked blood spots were ≥62% for amlodipine and simvastatin and ≥82% for the other target drugs. The assay sensitivity was sufficient to detect the drop in blood concentration, for all target drugs, resulting from missed doses. Conclusion: Ease of sampling data collected from participants’ show that VAMs devices was more user friendly compared to the DBS card. The developed microsampling based LC-HRMS assay has the potential to both assess medication adherence and to allow re-interrogation of the HRMS data collected for heart disease patients. This will enable health practitioners to monitor medication adherence. The 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.



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


Bernieh, D., Lawson, G. and Tanna, S. (2017) Performance of two different microsamplers for the LC-HRMS analysis of 10 cardiovascular drugs. 22nd International Reid Bioanalytical Forum, Cambourne, September 2017.


Research Institute

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