Direct injection human plasma analysis for the quantification of antihypertensive drugs for therapeutic drug monitoring using hydrophilic interaction liquid chromatography/electrospray ionization mass spectrometry.

Abstract The concept of personalized medicine is related to the development of new sensitive, precise and accurate analytical methods for therapeutic drug monitoring. In this article a rapid, sensitive and specific method was developed for the quantification of aliskiren, losartan, valsartan and hydrochlorothiazide in human plasma. Sample preparation was performed by protein precipitation with acetonitrile followed by filtration. All analytes and the internal standard (tiamulin) were separated by hydrophilic interaction liquid chromatography using an X-Bridge-HILIC analytical column (150.0 × 2.1 mm i.d., particle size 3.5 μm) under isocratic elution. The mobile phase was composed of a 10% 5 mM ammonium formate water solution pH 4.5, adjusted with formic acid, in acetonitrile and pumped at a flow rate of 0.25 mL min −1 . The assay was linear over the concentration range of 5–500 ng mL −1 for all the analytes. Intermediate precision was less than 5.2% over the tested concentration ranges. The method is the first reported application of HILIC in the analysis antihypertensives in human plasma. With a small sample size (50 μL human plasma) and a run time less than 6.0 min for each sample the method can be used to support a wide range of clinical studies and therapeutic drug monitoring.