Development and Validation of a UHPLC-MS/MS Method for the Simultaneous Quantification of Candesartan and Bisoprolol Together with Other 16 Antihypertensive Drugs in Plasma Samples

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