Evidence map›Paper›PMID 41807876›Full record

ArticleThe AAPS journal2026

Minimizing in Source Fragmentation for Mass Spectrometry Based NDSRI Analytical Procedures: A Case Study of Nitroso-bumetanide.

Jinhui Zhang, Mack Shih, Jingyue Yang, David A Keire, Xiaoming Xu, Patrick J Faustino

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Article in The AAPS journal, 2026. 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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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Jinhui ZhangOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA. Jinhui.Zhang@fda.hhs.gov.ORCID 0000-0002-1598-815X
Mack ShihOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Jingyue YangOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
David A KeireOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Xiaoming XuOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Patrick J FaustinoOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.ORCID 0000-0002-7719-0813

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

Liquid chromatography-mass spectrometry (LC-MS) is the standard instrumental procedure for quantitating nitrosamine drug substance-related impurities (NDSRIs) due to its superior specificity and sensitivity. Electrospray (ESI) is the most used ionization source in LC-MS. However, analytes can undergo fragmentation directly within the ESI source before reaching the collision cell. This phenomenon is known as in source fragmentation (ISF). To our knowledge, the impact of ISF on analytical procedure performance for NDSRI measurements has not been explored. Thus, here, we present a case study on an NDSRI (nitroso-bumetanide) to illustrate how efforts can be taken during analytical procedure development to minimize ISF while still achieving the analytical target profile (ATP) measurement goals. In addition, we share some thoughts about incorporating risk assessment and leveraging prior knowledge for analytical procedure development for NDSRI LC-MS technology-based testing purposes.

Indexed as

BumetanideDrug ContaminationLiquid Chromatography-Mass SpectrometryNitrosaminesSpectrometry, Mass, Electrospray IonizationMass SpectrometryBumetanideNitrosaminesanalytical procedure developmentin source fragmentationmass spectrometryNDSRI (Nitrosamine drug substance-related impurity)prior knowledgerisk assessment

Identifiers

PMID41807876
PMCPMC13011877

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.