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The first LC–HRMS method for the simultaneous quantification of the top ten UK prescribed cardiovascular drugs in dried blood spots developed.A micro-analytical method for monitoring medication adherence.Validation showed good linearity, accuracy and precision for the ten target drugs.Drug recoveries, sample stability and matrix effects were investigated.The validated method successfully identified control volunteers who were known to be either adherent or non-adherent.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 mm × 2.1 mm, 1.8 μm pore size column with the column oven temperature at 40 °C. Flow rate of the mobile phase was 0.6 ml/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 5 ppm 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.