Determination of ranolazine in rat plasma by liquid chromatography- electrospray ionization mass spectrometry

A rapid and sensitive liquid chromatographic-mass spectrometric (LC-MS) method, with phenoprolamine hydrochloride (DDPH) as internal standard, has been developed and validated for determination of ranolazine in rat plasma. After liquid-liquid extraction the compound was analyzed by HPLC on a C₁₈ column, with methanol-10 mM ammonium acetate, 76:24 (v/v), as mobile phase, coupled with electrospray ionization mass spectrometry (ESI-MS). The protonated analyte was quantified by selected-ion monitoring (SIM) with a quadrupole mass spectrometer in positive-ion mode. Calibration plots were linear over the concentration range 0.046-12 μg mL^-1. Inter and intra-day precision (CV%) and accuracy (RE%) for quality-control samples (0.187, 1.5, and 12 μg mL^-1) ranged between 2.96 and 13.38% and between -11.23 and 12.67%, respectively. Extraction recovery of RAN from plasma was in the range 82.77-86.54%. The method enables rapid, sensitive, precise, and accurate measurement of the concentration of ranolazine in rat plasma.