Time dependent selected reaction monitoring based enhanced sensitivity approach for the determination of alkyl sulfonates and anisyl cyanides in Venlafaxine hydrochloride by Gas chromatography with mass spectrometry

Abstract

Venlafaxine hydrochloride (VEN) is a newer generation antidepressant drug. Based on the synthetic procedure of VEN, formation of anisyl cyanides and alky sulfonates are possible. These impurities are known for their acute toxicity, come in the hazard and genotoxic class. Henceforth, it is necessity to control them in VEN at their acceptance level. Herein, sensitive t-SRM based gas chromatography coupled with triple-quadrupole mass spectrometry (GC–MS/MS) method has been developed for the trace level estimation of six potential impurities namely methyl methane sulfonate (MMS), ethyl methane sulfonate (EMS), isopropyl methane sulfonate (IPMS), o-anisyl cyanide (o-AC), m-anisyl cyanide (m-AC) and p-anisyl cyanide (p-AC); (alkyl sulfonates and anisyl cyanides) in VEN. The auto SRM tool was employed for the optimization of method parameters like SRM pair and collision energy to achieve the highest sensitivity. Various solvents as diluent were evaluated to optimize the extraction based recovery of all analyte. The method has been validated as per the ICH guideline (Q2R1). Obtained validation results proved the selectivity, sensitivity and robustness of the method. The correlation coefficient (r) values of all six impurities are more than 0.9988 in the range of 0.0003–0.6360 µg mL−1. Observed mean recoveries of all analytes are within the range of 93.21 to 97.77%. Method found to be capable to quantify of alkyl sulfonates and anisyl cyanides in the range of 4.5–24.1 ng g−1. Hence, the developed method is simple, direct, convenient, rapid and sensitive enough for its intended use in VEN trace impurity analysis.