Development and Validation of a LC-MS/MS Method for the Determination of Valsartan in Human Plasma after Protein Precipitation or Liquid-Liquid Extraction

Abstract

A rapid and specific liquid chromatographic mass/mass (LC-MS/MS) method is described for the assessment of valsartan (VAL) in human plasma after protein precipitation (PPT) and liquid-liquid extraction (LLE) techniques. The column used in PPT method was Eclipse Plus column, (C18, 50 mm x 2.1 mm, 1.8 μm) with a mobile phase ratio of 0.1% formic acid: methanol (15:85, v/v) while the column used in LLE method was Agilent column, (C18, 50 mm x 4.6 mm, 5 μm) with a mobile phase ratio of 0.1 % formic acid: acetonitrile (20:80, v/v). The assay was found to be linear over the ranges of 20-10000 and 25-8000 ng/ mL VAL using the PPT and LLE, respectively. The developed method was validated following the united states food and drug administration (US - FDA) recommendations and directions from the European Medical Agency (EMA). The method was validated for sensitivity, selectivity, linearity, accuracy and precision, recovery, dilution integrity, matrix effect, carryover in the matrix, and analyte stability during both short- and long-term sample processing and storage.