LC–MS/MS‐Based Method for the Determination of N‐Nitroso Venlafaxine EP Impurity‐H in Desvenlafaxine Succinate
TL;DR
The development and validation of a sensitive and selective LC–MS/MS method for the estimation of venlafaxine impurity‐H in desvenlafaxine succinate API is described and is suitable for routine quality control and regulatory compliance applications.
Abstract
Desvenlafaxine succinate, the major active metabolite of venlafaxine, is widely prescribed for the treatment of major depressive disorder. During synthesis and process optimization, structurally related impurities such as venlafaxine impurity‐H may be formed. Due to its structural similarity and potential toxicological concern, accurate trace‐level quantification of this impurity in desvenlafaxine succinate active pharmaceutical ingredient (API) is essential. The present study describes the development and validation of a sensitive and selective LC–MS/MS method for the estimation of venlafaxine impurity‐H in desvenlafaxine succinate API. Chromatographic separation was achieved on a C18 column under gradient elution using aqueous formic acid and methanol. Detection was performed in positive electrospray ionization mode using multiple reaction monitoring (MRM). The method was validated in accordance with ICH Q2(R2) guidelines and demonstrated excellent linearity ( r ≥ 0.995), acceptable precision, satisfactory recovery across the validated range, and high sensitivity. The developed method is suitable for routine quality control and regulatory compliance applications.