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Research Article Open access CC BY 4.0

Sensitive and Selective Analytical Method for the Quantification of Two Potential Genotoxic Impurities in Azilsartan Drug Substance by using LC-MS/MS with Multiple Reaction Monitoring (MRM mode)

Chandramohan Alluri, Kiran Kumar Naramsetti, G. Veera Raghava Sharma

Journal of Pharmaceutical Research International · pp. 467–478 · Published 29 Dec 2021

10.9734/jpri/2021/v33i63A36047

Abstract

The main aim of the present study to Synthesize,method development and method validation for quantification of two potential genotoxic impurities i.e., Methyl(Z)-2-ethoxy-1-((2'-(N'-hydroxycarbamimidoyl)-[1,1'-biphenyl]-4-yl) methyl)-1H-benzo[d]imidazole-7-carboxylate(Impurity-A) and 2-ethoxy-1-((2'-(N'-hydroxycarbamimidoyl[)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylicacid(Impurity-B) by using LC-MS/MS MRM mode at trace level determination inAzilsartan drug substance. The new LC-MS/MS MRM mode method was developed by using Inertsil ODS-3V 150x4.6mm,5µm column as stationary phase. The mobile phase used is the composition of 10Mm Ammonium formate pH3.00buffer:Acetonitrile(9:1)%v/v as mobilephase-A and 10Mm Ammonium formate pH3.00buffer:Acetonitrile(2:8)%v/v as mobile phase-B, isocratic  elution of mobile phase-A and Mobile phase-B (60:40)v/v at flow rate of 0.8mL/min.The concentration limits of the both genotoxic impurities were calculated a limit of 37.5ppm based on the concept of TTC (threshold of toxicological concern) and MDD (maximum daily dosage which is 40mg/day for Azilsartan drug substance.The limit of detection(LOD) was found to be 1.4ppm for both Impurity-A  and Impurity-B.The limit of quantification(LOQ) for Impurity-A was 4.7ppm and Impurity-B was 4.5ppm respectively The method was found to be linear from 4.7ppm to 78.4ppm for Impurity-A (correlation coefficient:1.000) and 4.5ppm to 75.7ppm for Impurity-B (correlation coefficient:0.999). The method was precise and found percentage of relative standard deviation for six replicate sample preparations of Impurity-A and Impurity-B was below 5.0%. The method accuracy was confirmed based on the recovery studies. Based on the method validation study method was sensitive and selective for quantification both genotoxic impurities.

LC-MS/MS MRM (Multiple reaction monitoring TTC (Threshold of toxicological concern) MDD (Maximum daily dosage) Azilsartan validation

References (6)

  1. 1 Forced degradation, LC–UV, MSn and LC–MS–TOF studies on azilsartan: Identification of a known and three new degradation impurities [DOI]
  2. 2 Synthesis of Azilsartan and Its Selected Potential Impurities [DOI]
  3. 3 Method Development and Validation for the Determination of Potential Impurities Present in Azilsartan medoxomil Tablets by Reverse Phase-Ultra Performance Liquid Chromatography [DOI]
  4. 4 Structural Elucidation of Potential Impurities in Azilsartan Bulk Drug by HPLC [DOI]
  5. 5 Synthesis and Characterization of Impurities of a Common and Advanced Intermediate of Candesartan and Azilsartan Antihypertensive Drugs [DOI]
  6. 6 Selective formation of a phenathridine derivative by photodegradation of azilsartan [DOI]

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