title: 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 (150.0×2.1mm i.d., particle size 3.5μm) under isocratic elution. The mobile phase was composed of a 10% 5mM ammonium formate water solution pH 4.5, adjusted with formic acid, in acetonitrile and pumped at a flow rate of 0.25mLmin(-1). The assay was linear over the concentration range of 5-500ngmL(-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 (50μL human plasma) and a run time less than 6.0min for each sample the method can be used to support a wide range of clinical studies and therapeutic drug monitoring.
authors.affiliation: University of Athens, School of Pharmacy, Division of Pharmaceutical Chemistry, Athens, Panepistimopolis-Zografou, 157 71 Athens, Greece.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Meimaroglou
authors.affiliation: University of Athens, School of Pharmacy, Division of Pharmaceutical Chemistry, Athens, Panepistimopolis-Zografou, 157 71 Athens, Greece.
authors.forename: Ariadni
authors.initials: A
authors.lastname: Vonaparti
authors.affiliation: Athens General Hospital "Alexandra", 80 Vas. Sofias Avenue, 115 28 Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Migias
authors.affiliation: Athens General Hospital "Korgialenio-Benakio National Red Cross" Erithrou Stavrou 1, 11526 Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Gennimata
authors.affiliation: Integrated Scientific Solutions, Protesilaou 101, 131 22 Athens, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Poulou
authors.affiliation: University of Athens, School of Pharmacy, Division of Pharmaceutical Chemistry, Athens, Panepistimopolis-Zografou, 157 71 Athens, Greece. Electronic address: ipanderi@pharm.uoa.gr.
authors.forename: Irene
authors.initials: I
authors.lastname: Panderi
mesh_terms: D000959:Antihypertensive Agents / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D057230:Limit of Detection; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000959:Antihypertensive Agents
keywords: Antihypertensive drugs; Direct injection analysis; Human plasma; Hydrophilic interaction liquid chromatography; Mass spectrometry; Therapeutic drug monitoring