Challenges in Simultaneous Determination of Hydrochlorothiazide and Ramipril in Human Plasma: Application to a Bioequivalence Study

An isotope dilution selective and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method has been developed for the simultaneous determination of hydrochlorothiazide (HCTZ) and ramipril in human plasma through a new concept of periodical polarity switching. Extraction of HCTZ, ramipril and their deuterated analogs as internal standards (ISs) was carried out from 150 μL of human plasma by solid-phase...