Automation of Routine HRMS Analysis for stress testing: lansoprazole as case study
August 2021. 61st Annual Land o’ Lakes Pharmaceutical Analysis Conference
Elisabeth Ortega-Carrasco, Luca Morettoni, Fabien Fontaine, Ismael Zamora
The purpose of this work is to show the automation workflow that can be achieve by using software tools (MassChemSite\WebChembase) for unsupervised and fast data processing and analysis to identify the degradation products of lansoprazole under multiple stress conditions (acid, base, neutral and oxidative stress).
Experimental data for the forced degradation study of lansoprazole was obtained following the ICH guidelines Q1A (R2). Lansoprazole was stressed under acidic (0.01 N HCl; room temperature; 60 min), basic (2N NaOH; 80 ⁰C; 72h), neutral (H2O/ACN 50:50, % v/v; 80 ⁰C; 48h) and oxidative (H2O2; room temperature; 60 min) stress conditions. Samples were analyzed via LC-HRMS using an Agilent Q-TOF 6450 coupled to an UV-Vis detector. Data processing was performed using the Derivatization workflow within the MassChemSite application (Molecular Discovery, Ltd). The processed data was consolidated by collecting all the samples for the same experimental condition and automatic comparison of the degradation products obtained in each sample.
The automatic approach provided to the researcher the structure of the different degradants found under the four mentioned conditions according to the m/z from the degradation reaction and the agreement between the structure of the degradation product and the MS/MS fragmentation. Moreover, kinetic parameters are also reported for the reactant compound degradation. Acidic stress condition resulted the most aggressive for lansoprazole drug being totally degraded in 60 minutes and generating lansoprazole sulfide as main degradant. For oxidative stress condition, the degradation reaction was stopped after 60 minutes, and lansoprazole was partially degraded to its oxidation product (lansoprazole sulphone). Under basic media, lansoprazole was almost unaltered. Last, under neutral conditions lansoprazole was totally degraded after 24h, generating two major degradants (the reduction product and a reorganization involving the loss of the sulfoxide group).
The automatic workflow has been proved as a valuable tool for general chemistry by automatize structural elucidation of reaction products.