Separation and Quantification of Key Starting Materials of Irbesartan Using Liquid Chromatography–Mass Spectrometry as a Separation and Identification Tool

Abstract

A liquid chromatography–mass spectrometry (LC-MS) method was developed and validated for determining the levels of 4-methyl-2-cyano biphenyl and 4-bromomethyl-2-cyano biphenyl, which are key starting materials of an antihypertensive drug substance, irbesartan. An active pharmaceutical ingredient of irbesartan was synthesized by using these two starting materials for its therapeutic use. We have explicated the LC-MS method to separate and quantify these two compounds in irbesartan at nanogram levels. The method was capable of separating irbesartan and its starting materials, which were monitored for their absence in the finished product of irbesartan. The separation was carried out at 40°C on a 150- × 4.6-mm cyano column by using the mobile phase containing 60 volumes of water adjusted to pH 3.2 with formic acid and 40 volumes of acetonitrile. The detection wavelength was 220 nm. The MS involved an electrospray ionization (ESI) probe and ion-trap analyzer and was validated with respect to its specificity, accuracy, and precision.

Keywords:

• 4-Methyl-2-cyano biphenyl and 4-bromomethyl-2-cyano biphenyl
• irbesartan
• LC-MS
• separation and quantification

We are grateful to Lee Pharma Laboratories for providing the batch samples of irbesartan and its key starting materials for the analysis.