LAUSR

Objective: Nowadays hypertension affects a large fraction of global population. Moreover, 15–30% of patients show drug-resistance, needing the addition of more drugs; meanwhile, polytherapy often results in poor therapeutic adherence, classified as “pseudo-resistant” hypertension. In this context, Therapeutic Drug Monitoring (TDM) of antihypertensive drugs, which consists in the measurement of drug concentration in biological matrices, may help to discern problems in drug pharmacokinetics/pharmacodynamics from cases of poor therapeutic adherence, also considering that not-pharmacological alternative consists in invasive surgery. It has been hence validated an UHPLC-MS/MS method for simultaneous TDM on plasma samples of ten antihypertensive drugs: amlodipine, atenolol, clonidine, chlortalidone, doxazosin, hydrochlorothiazide, nifedipine, olmesartan, ramipril and telmisartan. Design and method: This method has been validated according to FDA guidelines. 200 &mgr;l of sample, standard and quality control, added with 40 &mgr;l of internal standard working solution, undergo a simple protein precipitation protocol, followed by drying step, and resulting extracts are resuspended in water:acetonitrile 90:10 (v:v; +0.05% formic acid) and then analyzed through a Shimadzu NexeraX2® UHPLC system coupled with a LCMS-8050® tandem mass detector. The validated method was tested on real samples from patients with RH/pseudo-RH, all giving informed consent. Results: All analytical parameters of the method fitted FDA guidelines for all the analytes. 42 patients have been enrolled (SEAL study). TDM revealed that 55% of patients (n = 23) had detectable concentration of all prescribed drugs (considered fully adherent), 26% (n = 11) resulted partially non-adherent (only part of the prescribed drugs was detectable) and 19% (n = 8) were totally not-adherent (no drugs were detected). Through univariate/multivariate logistic regression, the diastolic pressure and the “white-coat” increase in heart rate resulted the best predictors of poor adherence. Through ROC curve analysis a diastolic pressure over 124 mmHg resulted predictive of total inadherence. Conclusions: TDM can be a gold-standard for evaluating therapeutic adherence and this method results eligible for a clinical routine use. We managed to discern cases of inadherence, preserving some patients from an invasive and expensive surgery. Figure. No caption available.