Quantitative LC-HRMS determination of selected cardiovascular drugs, in dried blood spots, as an indicator of adherence to medication

Date

2017-05-06

Advisors

Journal Title

Journal ISSN

ISSN

0731-7085

Volume Title

Publisher

Elsevier

Type

Article

Peer reviewed

Yes

Abstract

Dried blood spot (DBS) sampling was investigated as a means of obtaining micro-volume blood samples for the quantitative analyses of ten commonly UK prescribed cardiovascular drugs as an indicator of medication adherence. An 8 mm disc was punched out from each DBS from calibration, quality control and volunteer samples and extracted using methanol containing the internal standard. Each extract was evaporated to dryness, the residue reconstituted in methanol:water (40:60 v/v) containing 0.1% formic acid and analysed by LC-HRMS. Chromatography was performed using gradient elution on a Zorbax Eclipse C18 HD 100 mmx2.1 mm, 1.8 µm pore size column with the column oven temperature at 40˚C. Flow rate of the mobile phase was 0.6ml/min with a run time of 2.5 min. Electrospray positive ionization was used for MS detection. Drug recoveries from spiked blood spots were 68% for simvastatin and ≥ 87% for all other target drugs. Compound specificity was obtained operating the MS with a 5ppm mass window. The LC-HRMS method was validated, with results for accuracy and precision within acceptable limits; analytes were stable at room temperature for at least 10 weeks and different blood spot volumes and haematocrit values had no significant effect. The LC-HRMS assay was used to analyse DBS samples from volunteers, some of whom were prescribed one or more of the target drugs. In results from 37 volunteers the assay successfully identified volunteers who were known to be either adherent or nonadherent; confirmed the correct drug/drugs for multiple prescriptions; demonstrated no false positives from other cardiovascular drugs; revealed several examples of unsuspected non-adherence. These results indicated that the developed assay was suitable for trials with patients.

Description

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.

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. (2017) Quantitative LC-HRMS determination of selected cardiovascular drugs, in dried blood spots, as an indicator of adherence to medication. Journal of Pharmaceutical and Biomedical Analysis, 142, pp. 232-243

Rights

Research Institute

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