Tag Archives: 2021

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

Abstract

Results:

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).

Conclusions:

The automatic workflow has been proved as a valuable tool for general chemistry by automatize structural elucidation of reaction products.

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Development, optimization and implementation of a centralized metabolic soft spot assay

April 2017

Anthony A Paiva, Cheryl Klakouski, Shu Li, Benjamin M Johnson, Yue-Zhong Shu, Jonathan Josephs, Tatyana Zvyaga, Ismael Zamora, Wilson Z Shou

Abstract

Keywords

Dual-concentration incubation; metabolic soft spot; metabolic stability; orthogonal sample pooling; software assisted data processing.

Automatic Identification of Lansoprazole Degradants under Stress Conditions by LC-HRMS with MassChemSite and WebChembase

June 2021.

Stefano Bonciarelli, Jenny Desantis*, Laura Goracci, Lydia Siragusa, Ismael Zamora, Elisabeth Ortega-Carrasco*

Abstract

Stress testing is one of the most important parts of the drug development process, helping to foresee stability problems and to identify degradation products. One of the processes involving stress testing is represented by forced degradation studies, which can predict the impact of certain conditions of pH, moisture, heat, or other negative effects due to transportation or packaging issues on drug potency and purity, ensuring patient safety. Regulatory agencies have been working on a standardization of laboratory procedures since the past two decades. One of the results of those years of intensive research is the International Conference on Harmonization (ICH) guidelines, which clearly define which forced degradation studies should be performed on new drugs, which become a routine work in pharmaceutical laboratories. Since used techniques based on high-performance liquid chromatography coupled with high-resolution mass spectrometry have been developed years ago and are now mastered by pharmaceutical scientists, automation of data analysis, and thus data processing, is becoming a hot topic nowadays. In this work, we present MassChemSite and WebChembase as a tandem to automatize the routine analysis studies without missing information quality, using as a case study the degradation of lansoprazole under acidic, oxidative, basic, and neutral stress conditions.

Mass spectrometry imaging of phosphatidylcholine metabolism in lungs administered with therapeutic surfactants and isotopic tracers

January 2021.

Shane R. Ellis, Emily Hall, Madhuriben Panchal, Bryn Flinders, Jens Madsen, Grielof Koster, Ron.M.A. Heeren, Howard W. Clark, Anthony D. Postle 

Abstract

Mass spectrometry imaging (MSI) visualizes molecular distributions throughout tissues but is blind to dynamic metabolic processes. Here, MSI with high mass resolution together with multiple stable isotope labelling provided spatial analyses of phosphatidylcholine (PC) metabolism in mouse lungs. 

Dysregulated surfactant metabolism is central to many respiratory diseases. Metabolism and turnover of therapeutic pulmonary surfactants were imaged from distributions of intact and metabolic products of an added tracer, universally 13C-labelled dipalmitoyl PC (U13C-DPPC). The parenchymal 

distributions of newly synthesized PC species were also imaged from incorporations of methyl-D9- choline. This dual labelling strategy demonstrated both lack of inhibition of endogenous PC synthesis by exogenous surfactant and location of acyl chain remodeling processes acting on the U13C-DPPClabelled surfactant, leading to formation of polyunsaturated PC lipids. This ability to visualize discrete metabolic events will greatly enhance our understanding of lipid metabolism in diverse tissues and has potential application to both clinical and experimental studies.