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.

► An assay for the determination of KRN1493 using LC–MS/MS in MRM mode was developed.
► The method required small plasma volume and presented high throughput analysis.
► The present method was validated according to FDA guideline.
► This method was applied to the PK studies of KRN1493 in Chinese healthy volunteers.