A Non-Invasive Method for Detection of Antihypertensive Drugs in Biological Fluids: The Salivary Therapeutic Drug Monitoring

Valeria Avataneo; Elvira Fanelli; Amedeo De Nicolò; Franco Rabbia; Alice Palermiti; Marco Pappaccogli; Jessica Cusato; Francesco Giuseppe De Rosa; Antonio D'Avolio; Franco Veglio

doi:10.3389/fphar.2021.755184

A Non-Invasive Method for Detection of Antihypertensive Drugs in Biological Fluids: The Salivary Therapeutic Drug Monitoring

Front Pharmacol. 2022 Jan 5:12:755184. doi: 10.3389/fphar.2021.755184. eCollection 2021.

Affiliations

¹ Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.
² Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, A.O.U. Città Della Salute e Della Scienza di Torino, University of Turin, Turin, Italy.
³ Division of Infectious Diseases, Department of Medical Sciences, A.O.U. Città Della Salute e Della Scienza di Torino, University of Turin, Turin, Italy.

Abstract

Objectives: Arterial hypertension is still the most frequent cause of cardiovascular and cerebrovascular morbidity and mortality. Antihypertensive treatment has proved effective in reduction of cardiovascular risk. Nevertheless, lifestyle interventions and pharmacological therapy in some cases are ineffective in reaching blood pressure target values, despite full dose and poly-pharmacological treatment. Poor adherence to medications is an important cause of treatment failure. Different methods to assess therapeutic adherence are currently available: Therapeutic drug monitoring in biological fluids has previously demonstrated its efficacy and reliability. Plasma and urine have been already used for this purpose, but they may be affected by some practical limitations. Saliva may represent a feasible alternative. Methods: Fourteen antihypertensive drugs and two metabolites were simultaneously tested in plasma, urine, and saliva. Tested molecules included: atenolol, nebivolol, clonidine, ramipril, olmesartan, telmisartan, valsartan, amlodipine, nifedipine, doxazosin, chlorthalidone, hydrochlorothiazide, indapamide, sacubitril, ramiprilat, and sacubitrilat. Therapeutic drug monitoring was performed using ultra-high performance liquid chromatography, coupled to tandem mass spectrometry (UHPLC-MS/MS). The method has been preliminarily evaluated in a cohort of hypertensive patients. Results: The method has been validated according to US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The application on a cohort of 32 hypertensive patients has demonstrated sensibility and specificity of 98% and 98.1%, respectively, with a good feasibility in real-life clinical practice. Conclusion: Saliva may represent a feasible biological sample for therapeutic drug monitoring by non-invasive collection, prompt availability, and potential accessibility also in out-of-clinic settings.

Keywords: antihypertensive drugs; hypertension; liquid chromatography; tandem mass spectrometry; therapeutic drug monitoring.