Development\nand Validation of a UHPLC-MS/MS Method\nfor the Simultaneous Quantification of Candesartan and Bisoprolol\nTogether with Other 16 Antihypertensive Drugs in Plasma Samples

Antihypertensive pharmacological therapy is often characterized\nby a coadministration of different classes of drugs. Therefore, analytical\nmethods allowing the simultaneous quantification of many drugs are\nneeded for therapeutic drug monitoring (TDM) purposes in this context.\nIn particular, TDM represents a useful tool to discriminate poor adherence\nfrom real cases of resistant hypertension. For this reason, the aim\nof this study is to validate, following the Food and Drug Administration\n(FDA) and the European Medicines Agency (EMA) guidelines, an ultrahigh-performance\nliquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS)\nmethod for the simultaneous quantification of 18 antihypertensive\ndrugs in human plasma. A LX-50 coupled with a QSight 220 UHPLC-MS/MS\nsystem with electrospray ionization and multiple reaction monitoring\nmode was used, after a binary gradient separation (13 min) on a reverse-phase\nAcquity UPLC HSS T3 [1.8 μm, 2.1 mm × 150 mm] column. Method\nvalidation showed a stable and acceptable matrix effect, recovery,\nhigh accuracy, and precision, assessing the eligibility of this method\nfor routine use in the clinical context.