Development of an LC-MS/MS method to quantitatively analyze escitalopram and its metabolites with application in liver and placenta microsome metabolism.

Yifei Shen, Bingyi Yao, Yuanqing Guo, Yujia Yang, Chenmeizi Liang, Junze Huang, Yuanjin Zhang, Xin Wang

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Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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8 authors.

Yifei Shen *Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.

Bingyi Yao *Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.

Yuanqing Guo *Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.

Yujia YangChangning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.

Chenmeizi LiangChangning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.

Junze HuangChangning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.

Yuanjin ZhangChangning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.

Xin WangChangning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Escitalopram (SCT), a highly effective and low-risk antidepressant, is widely used in the clinical treatment of depression. It undergoes two N-demethylation steps, producing its primary metabolites, S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT). Purpose: This study aimed to develop and validate an LC-MS/MS method to simultaneously detect SCT, S-DCT, and S-DDCT, and then apply it to study metabolism in different microsomes, comparing SCT metabolism in rat liver microsomes (RLM), human liver microsomes (HLM), and human placenta microsomes (HPM). Methods: This study developed a reliable LC-MS/MS method for the simultaneous detection of escitalopram and its metabolites in various microsomal systems. The method was fully validated in rat liver microsomes and then was applied into human liver and placenta microsomes. The method was further applied to investigate escitalopram metabolism in different microsomal systems, notably for the first time in human placenta microsomes. Results: LC-MS/MS method provides high specificity, good stability, and excellent extraction recovery. Both intra-day and inter-day accuracy (% RE) and precision (% RSD) were within ±15%, with no significant matrix effects observed. The metabolic rates of escitalopram and its metabolite levels differed among rat liver, human liver, and human placenta microsomes, likely due to variations in the types and activities of drug-metabolizing enzymes present in these systems. Conclusion: A sensitive and reliable LC-MS/MS method was developed and validated for the quantitative analysis of SCT, S-DCT, and S-DDCT in RLM. Subsequently, the method was applied to the study of HLM and HPM. Incubation experiments using these microsomal systems showed that all three types of microsomes, including HPM, could metabolize SCT.

Indexed as

escitalopramhuman placenta microsomesLC-MS/MSLiver microsomesmetabolism

Identifiers

PMID41458971

DOI10.3389/fphar.2025.1714686

PMCPMC12741097

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