Indexed plasma drug concentrations for drug adherence screening in hypertensive patients

Due to its high sensitivity, qualitative plasma drug screening by liquid chromatography/tandem mass spectrometry may not be able to distinguish same-day drug intake from drug use on preceding days and cause misclassifications of drug adherence in hypertensive patients. Analysis of plasma drug concentrations may provide more accurate results.

We describe dose-dependent indexing of plasma drug concentrations for expected peak concentrations to define individual screening thresholds for same-day drug use. To explore its utility, plasma samples from 9 hypertensive patients without major comorbidity were prospectively analyzed on two occasions. All were on hydrochlorothiazide with either amlodipine (n=7) and/or valsartan (n=6) at different doses. Drugs were quantitated by mass spectrometry. Non-adherence was defined if an indexed drug concentration was below the expected trough level at 24-hour dosing interval.

All patients were adherent by qualitative plasma screening (spectrometric sensitivity). On the first visit (random sampling time), mean plasma concentrations of the drugs were 102±70, 15.4±6.7 and 2529±1608ng/mL, and mean indexes 84±57%, 85±35% and 60±38%, respectively. Using the study criterion, non-adherence was suspected in three. Intraindividual cross-checking retained two. On the second visit (fixed sampling time), amlodipine concentration was 15.6±8.5ng/mL (88±52% after indexing). Two patients were non-adherent according to the study criterion.

Indexing of plasma drug concentrations appears practicable and useful for drug adherence screening under clinical conditions. With this technique, same-day drug intake can be easily distinguished which reduces the risk of false positive results associated with qualitative drug screening.