Determination of cinacalcet hydrochloride in human plasma by liquid chromatography-tandem mass spectrometry.

A sensitive and selective high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the cinacalcet hydrochloride in human plasma. The analyte was extracted from plasma samples using a 96-well plate automatic solid-phase extraction (SPE) device and chromatographed on an Inertsil SIL-150 (2.1 mm × 50 mm, i.d. 5 μm) column using acetonitrile-water-formic acid (90:10:1) as the mobile phase with an isocratic flow rate of 0.35 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). The method was validated over the concentration range of 0.1-25 ng/mL. The indicators of inter- and intra-day precision (RSD%) were all within 15.1%, and the accuracy (RE%) was within ± 15%. The lower limit of quantitation (LLOQ) was 0.1 ng/mL. The average extraction recovery was 51.7%, and the detection was not affected by the matrix. The method was successfully applied to a pharmacokinetic study of cinacalcet hydrochloride in healthy Chinese volunteers.