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Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay

Screening for possible interferences from steroidal compounds other than the target analytes (endogenous or exogenous) is well established in LC-MS/MS assay development for steroid quantification in a routine clinical setting. However, interferences from non-steroidal substances have, hitherto, not...

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Autores principales: Braun, Valentin, Stuppner, Hermann, Seger, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856384/
https://www.ncbi.nlm.nih.gov/pubmed/36672264
http://dx.doi.org/10.3390/cells12020329
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author Braun, Valentin
Stuppner, Hermann
Seger, Christoph
author_facet Braun, Valentin
Stuppner, Hermann
Seger, Christoph
author_sort Braun, Valentin
collection PubMed
description Screening for possible interferences from steroidal compounds other than the target analytes (endogenous or exogenous) is well established in LC-MS/MS assay development for steroid quantification in a routine clinical setting. However, interferences from non-steroidal substances have, hitherto, not been explored. After screening more than 150 pharmaceuticals and their metabolites by analyzing commercial quality control samples from TDM analysis kits (Recipe, Chromsystems) with a multisteroid LC-MS/MS assay (protein precipitation followed by HybridSPE filtration, biphenyl column, methanol–water gradient with NH4F additive), we can report the finding of two newly discovered potential interferences from non-steroidal drugs. Antidepressant paroxetine (PX) was identified as an interference to 17-hydroxyprogesterone (17P), and α-hydroxytriazolam (α-OH-TZM)—a major metabolite of benzodiazepine triazolam (TZM)—was identified as an interference to aldosterone (ALDO). Despite different elemental and structural compositions and nominal masses, the M+1 isotopologues of PX and α-OH-TZM produced overlapping signals in ion traces monitored for the respective analytes (m/z 331 → 109/97 and 361→315/343, respectively). PX and TZM are frequently prescribed drugs, and their therapeutic ranges are far exceeding the reference ranges of 17P or ALDO (µmol vs nmol); therefore, these interferences should be considered clinically relevant. Striving for faster multi-analyte methods with high sample turnover, especially in the field of steroid quantification, can limit assay selectivity and specificity. Therefore, supported by the findings of this study, screening for potential interferences in multi-analyte LC-MS/MS method development should not cover only substances of the same class but also include a set of common drugs.
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spelling pubmed-98563842023-01-21 Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay Braun, Valentin Stuppner, Hermann Seger, Christoph Cells Communication Screening for possible interferences from steroidal compounds other than the target analytes (endogenous or exogenous) is well established in LC-MS/MS assay development for steroid quantification in a routine clinical setting. However, interferences from non-steroidal substances have, hitherto, not been explored. After screening more than 150 pharmaceuticals and their metabolites by analyzing commercial quality control samples from TDM analysis kits (Recipe, Chromsystems) with a multisteroid LC-MS/MS assay (protein precipitation followed by HybridSPE filtration, biphenyl column, methanol–water gradient with NH4F additive), we can report the finding of two newly discovered potential interferences from non-steroidal drugs. Antidepressant paroxetine (PX) was identified as an interference to 17-hydroxyprogesterone (17P), and α-hydroxytriazolam (α-OH-TZM)—a major metabolite of benzodiazepine triazolam (TZM)—was identified as an interference to aldosterone (ALDO). Despite different elemental and structural compositions and nominal masses, the M+1 isotopologues of PX and α-OH-TZM produced overlapping signals in ion traces monitored for the respective analytes (m/z 331 → 109/97 and 361→315/343, respectively). PX and TZM are frequently prescribed drugs, and their therapeutic ranges are far exceeding the reference ranges of 17P or ALDO (µmol vs nmol); therefore, these interferences should be considered clinically relevant. Striving for faster multi-analyte methods with high sample turnover, especially in the field of steroid quantification, can limit assay selectivity and specificity. Therefore, supported by the findings of this study, screening for potential interferences in multi-analyte LC-MS/MS method development should not cover only substances of the same class but also include a set of common drugs. MDPI 2023-01-15 /pmc/articles/PMC9856384/ /pubmed/36672264 http://dx.doi.org/10.3390/cells12020329 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Braun, Valentin
Stuppner, Hermann
Seger, Christoph
Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay
title Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay
title_full Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay
title_fullStr Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay
title_full_unstemmed Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay
title_short Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay
title_sort non-steroidal drug interferences in a quantitative multisteroid lc-ms/ms assay
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856384/
https://www.ncbi.nlm.nih.gov/pubmed/36672264
http://dx.doi.org/10.3390/cells12020329
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