Determination of aliskiren in human serum quantities by HPLC-tandem mass spectrometry appropriate for pediatric trials.

Biomedical chromatography : BMC

PubMedID: 23055424

Burckhardt BB, Ramusovic S, Tins J, Laeer S. Determination of aliskiren in human serum quantities by HPLC-tandem mass spectrometry appropriate for pediatric trials. Biomed Chromatogr. 2013;27(4):477-86.
The orally active direct renin inhibitor aliskiren is approved for the treatment of essential hypertension in adults. Analytical methods utilized in clinical studies on efficacy and safety have not been fully described in the literature but need a large sample volume ranging from 200 to 700 µL, rendering them unsuitable particularly for pediatric applications. In the assay presented only 100 µL of serum is needed for mixed-mode solid-phase extraction. The chromatographic separation was performed on Xselect(TM) C18 CSH columns with mobile phase consisting of methanol-water-formic acid (75:25:0.005, v/v/v) and a flow rate of 0.4?mL/min. Running in positive electrospray ionization and multiple reaction monitoring the mass spectrometer was set to analyze precursor ion 552.2?m/z [M?+?H](+) to product ion 436.2?m/z during a total run time of 5?min. The method covers a linear calibration range of 0.146-1200?ng/mL. Intra-run and inter-run precisions were 0.4-7.2 and 0.6-12.9%. Mean recovery was at least 89%. Selectivity, accuracy and stability results comply with current European Medicines Agency and Food and Drug Administration guidelines. This successfully validated LC-MS/MS method with a wide linear calibration range requiring small serum amounts is suitable for pharmacokinetic investigations of aliskiren in pediatrics, adults and the elderly.