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.