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Accelerating Pharmaceutical Process Development with an Acoustic Droplet Ejection-Multiple Reaction Monitoring-Mass Spectrometry Workflow.
Hu, Hang; Singh, Andrew N; Lehnherr, Dan; Mdluli, Velabo; Chun, Stephanie W; Makarewicz, Amanda M; Gouker, Joseph R; Ukaegbu, Ophelia; Li, Shasha; Wen, Xiujuan; McLaren, David G; Velasquez, Juan E; Moore, Jeffrey C; Galanie, Stephanie; Appiah-Amponsah, Emmanuel; Regalado, Erik L.
Afiliação
  • Hu H; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Singh AN; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Lehnherr D; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Mdluli V; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Chun SW; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Makarewicz AM; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Gouker JR; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Ukaegbu O; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Li S; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Wen X; Quantitative Biosciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • McLaren DG; Quantitative Biosciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Velasquez JE; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Moore JC; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Galanie S; Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Appiah-Amponsah E; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
  • Regalado EL; Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Anal Chem ; 96(3): 1138-1146, 2024 01 23.
Article em En | MEDLINE | ID: mdl-38165811
ABSTRACT
Fast-paced pharmaceutical process developments (e.g., high-throughput experimentation, directed evolution, and machine learning) involve the introduction of fast, sensitive, and accurate analytical assays using limited sample volumes. In recent years, acoustic droplet ejection (ADE) coupled with an open port interface has been invented as a sampling technology for mass spectrometry, providing high-throughput nanoliter analytical measurements directly from the standard microplates. Herein, we introduce an ADE-multiple reaction monitoring-mass spectrometry (ADE-MRM-MS) workflow to accelerate pharmaceutical process research and development (PR&D). This systematic workflow outlines the selection of MRM transitions and optimization of assay parameters in a data-driven manner using rapid measurements (1 sample/s). The synergy between ADE sampling and MRM analysis enables analytical assays with excellent sensitivity, selectivity, and speed for PR&D reaction screenings. This workflow was utilized to develop new ADE-MRM-MS assays guiding a variety of industrial processes, including (1) screening of Ni-based catalysts for C-N cross-coupling reaction at 1 Hz and (2) high-throughput regioisomer analysis-enabled enzyme library screening for peptide ligation reaction. ADE-MRM-MS assays were demonstrated to deliver accurate results that are comparable to conventional liquid chromatography (LC) experiments while providing >100-fold throughput enhancement.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Desenvolvimento de Medicamentos Tipo de estudo: Prognostic_studies Idioma: En Revista: Anal Chem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Desenvolvimento de Medicamentos Tipo de estudo: Prognostic_studies Idioma: En Revista: Anal Chem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos