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A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats

Benzodiazepines potentiate respiratory depression when combined with an opioid leading the U.S Food and Drug Administration (FDA) to recommend updating the labels of these products with a boxed warning for respiratory depression with co-use. Potential respiratory depression upon co-administration of...

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Autores principales: Pilli, Nageswara R., Narayanasamy, Suresh, Xu, Lin, Chockalingam, Ashok, Shea, Katherine I., Stewart, Sharron, Rouse, Rodney, Patel, Vikram, Matta, Murali K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047970/
https://www.ncbi.nlm.nih.gov/pubmed/35494453
http://dx.doi.org/10.1039/c9ra05785d
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author Pilli, Nageswara R.
Narayanasamy, Suresh
Xu, Lin
Chockalingam, Ashok
Shea, Katherine I.
Stewart, Sharron
Rouse, Rodney
Patel, Vikram
Matta, Murali K.
author_facet Pilli, Nageswara R.
Narayanasamy, Suresh
Xu, Lin
Chockalingam, Ashok
Shea, Katherine I.
Stewart, Sharron
Rouse, Rodney
Patel, Vikram
Matta, Murali K.
author_sort Pilli, Nageswara R.
collection PubMed
description Benzodiazepines potentiate respiratory depression when combined with an opioid leading the U.S Food and Drug Administration (FDA) to recommend updating the labels of these products with a boxed warning for respiratory depression with co-use. Potential respiratory depression upon co-administration of opioids with some psychotropic drugs is not well understood. The FDA is currently investigating various psychotropic drug interactions with the commonly used opioid, oxycodone, in a rat model assessing respiratory depression. Pharmacokinetic and/or pharmacodynamic (PK/PD) interaction between oxycodone and diazepam was evaluated in a positive control arm of these experiments. Understanding the systemic exposure of these drugs alone and in combination exposures was used to identify PK/PD interactions. The authors developed a simple, high throughput liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for the simultaneous determination of oxycodone and diazepam in rat plasma. Sample preparation was performed in 96-well protein precipitation plates using acetonitrile. Processed samples were analyzed using a C(18) column with a gradient mobile phase composed of 2 mM aqueous ammonium formate with 0.1% formic acid and acetonitrile. A Thermo TSQ Quantum Ultra AM triple quadrupole mass spectrometer with multiple reaction monitoring (MRM) mode was used to acquire data. The method was validated for selectivity, specificity, linearity, precision and accuracy, dilution integrity and stability. The validated LC-MS/MS assay was utilized for quantifying oxycodone and diazepam in concomitantly treated Sprague Dawley (SD) rats.
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spelling pubmed-90479702022-04-28 A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats Pilli, Nageswara R. Narayanasamy, Suresh Xu, Lin Chockalingam, Ashok Shea, Katherine I. Stewart, Sharron Rouse, Rodney Patel, Vikram Matta, Murali K. RSC Adv Chemistry Benzodiazepines potentiate respiratory depression when combined with an opioid leading the U.S Food and Drug Administration (FDA) to recommend updating the labels of these products with a boxed warning for respiratory depression with co-use. Potential respiratory depression upon co-administration of opioids with some psychotropic drugs is not well understood. The FDA is currently investigating various psychotropic drug interactions with the commonly used opioid, oxycodone, in a rat model assessing respiratory depression. Pharmacokinetic and/or pharmacodynamic (PK/PD) interaction between oxycodone and diazepam was evaluated in a positive control arm of these experiments. Understanding the systemic exposure of these drugs alone and in combination exposures was used to identify PK/PD interactions. The authors developed a simple, high throughput liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for the simultaneous determination of oxycodone and diazepam in rat plasma. Sample preparation was performed in 96-well protein precipitation plates using acetonitrile. Processed samples were analyzed using a C(18) column with a gradient mobile phase composed of 2 mM aqueous ammonium formate with 0.1% formic acid and acetonitrile. A Thermo TSQ Quantum Ultra AM triple quadrupole mass spectrometer with multiple reaction monitoring (MRM) mode was used to acquire data. The method was validated for selectivity, specificity, linearity, precision and accuracy, dilution integrity and stability. The validated LC-MS/MS assay was utilized for quantifying oxycodone and diazepam in concomitantly treated Sprague Dawley (SD) rats. The Royal Society of Chemistry 2020-01-03 /pmc/articles/PMC9047970/ /pubmed/35494453 http://dx.doi.org/10.1039/c9ra05785d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Pilli, Nageswara R.
Narayanasamy, Suresh
Xu, Lin
Chockalingam, Ashok
Shea, Katherine I.
Stewart, Sharron
Rouse, Rodney
Patel, Vikram
Matta, Murali K.
A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats
title A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats
title_full A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats
title_fullStr A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats
title_full_unstemmed A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats
title_short A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats
title_sort high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in sprague dawley rats
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047970/
https://www.ncbi.nlm.nih.gov/pubmed/35494453
http://dx.doi.org/10.1039/c9ra05785d
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