LC-MS characterization of acid degradation products of metoclopramide: Development and validation of a stability-indicating RP-HPLC method

Abstract

The present study aims to develop a simple, accurate and specific stability-indicating RP-HPLC technique for the analysis of metoclopramide in the presence of its stress degradation products and characterization of degradation compounds by LC-MS/MS analysis. As per ICH Q1A-R2 guidelines, the drug was exposed to acid hydrolytic stress condition. Three degradation products were formed for MCP in acid hydrolysis. The liquid chromatography was processed on a Luna C18-(2) 100A,250×4.6mm 5micron column using an isocratic mobile phase consisting of 0.1% formic acid in water-acetonitrile (20:80, v/v) by adjusting the mobile phase at 1 ml/min flow rate with wavelength detection at 273 nm. The developed procedure was applied to LC-MS/MS (liquid chromatography-tandem mass spectrometry) for the characterization of all the degradant components. Total new three degradation compounds were recognized and identified by LC-MS/MS. The developed RP-HPLC technique was validated as per the ICH Q2-R1 guidelines. Limit of detection and limit of quantification values of MCP were evaluated from the linearity graph and were found to be 5.23 µg/ml and 17.44 µg/ml. Accuracy study was established at 80.0, 100.0 and 120.0 µg/ml concentration levels and the findings were found in the range of 98.4% - 101.8%. The linearity of the technique was assessed over the drug concentration range of 50.0 µg/ml to 250.0 µg/ml and the regression equation, slope and correlation coefficient values were found to be y = 10618x + 1623.2, 10618 and 0.9996 respectively. The developed technique was uninterruptedly applied for the quantification of metoclopramide inactive pharmaceuticals.