Simple and sensitive assay for quantification of oseltamivir and its active metabolite oseltamivir carboxylate in human plasma using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry

Improved applicability to pharmacokinetic study

Zhe Yi Hu, Steven Laizure, Bernd Meibohm, Vanessa L. Herring, Robert Parker

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Although liquid chromatography/electrospray ionization tandem mass spectrometry-based assays have been reported for the measurement of the antiviral oseltamivir (OS) in human samples, these assays either involve complicated sample pretreatment or lack sensitivity. Here we introduce a straightforward approach to improve the assay performance for OS and its metabolite oseltamivir carboxylate (OSC) in human plasma. A very low concentration of mobile phase modifier can improve the ionization efficiency of both analytes, thus enabling a high sensitivity without any matrix effect. The fast LC gradient further increases the sensitivity by narrowing the peak width (6-9. s) and eluting the analytes at higher organic content. The increased ionization efficiency and minimized matrix effects enabled us to introduce a one-step protein precipitation for sample clean-up without compromising the sensitivity. The lower limit of quantification was 0.34. ng/mL for both analytes, which was at least 3 times more sensitive than published assays that involve complicated sample pretreatment. The assay involves measurement of analytes and their stable-isotope internal standards in small-volume (30-μL) plasma. Sodium fluoride was utilized to prevent the hydrolysis of OS during and after sampling. The calibration curve was linear over the range of 0.34-1000. ng/mL. Accuracy was 95-110% and the precision was 2.2-11.0%. This method was applied successfully to the human pharmacokinetic study of OS, and can estimate the relevant pharmacokinetic parameters of OS with more accuracy. The approach utilized in the optimization of assay performance can be extended to the measurement of other drugs in biomatrices.

Original languageEnglish (US)
Pages (from-to)245-250
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume72
DOIs
StatePublished - Jan 18 2013

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Plasma (human)
Oseltamivir
Electrospray ionization
Pharmacokinetics
Electrospray Ionization Mass Spectrometry
High performance liquid chromatography
Metabolites
Tandem Mass Spectrometry
Mass spectrometry
Assays
High Pressure Liquid Chromatography
Ionization
Sodium Fluoride
Liquid Chromatography
Isotopes
Liquid chromatography
Calibration
Antiviral Agents
Hydrolysis
oseltamivir carboxylate

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

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title = "Simple and sensitive assay for quantification of oseltamivir and its active metabolite oseltamivir carboxylate in human plasma using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry: Improved applicability to pharmacokinetic study",
abstract = "Although liquid chromatography/electrospray ionization tandem mass spectrometry-based assays have been reported for the measurement of the antiviral oseltamivir (OS) in human samples, these assays either involve complicated sample pretreatment or lack sensitivity. Here we introduce a straightforward approach to improve the assay performance for OS and its metabolite oseltamivir carboxylate (OSC) in human plasma. A very low concentration of mobile phase modifier can improve the ionization efficiency of both analytes, thus enabling a high sensitivity without any matrix effect. The fast LC gradient further increases the sensitivity by narrowing the peak width (6-9. s) and eluting the analytes at higher organic content. The increased ionization efficiency and minimized matrix effects enabled us to introduce a one-step protein precipitation for sample clean-up without compromising the sensitivity. The lower limit of quantification was 0.34. ng/mL for both analytes, which was at least 3 times more sensitive than published assays that involve complicated sample pretreatment. The assay involves measurement of analytes and their stable-isotope internal standards in small-volume (30-μL) plasma. Sodium fluoride was utilized to prevent the hydrolysis of OS during and after sampling. The calibration curve was linear over the range of 0.34-1000. ng/mL. Accuracy was 95-110{\%} and the precision was 2.2-11.0{\%}. This method was applied successfully to the human pharmacokinetic study of OS, and can estimate the relevant pharmacokinetic parameters of OS with more accuracy. The approach utilized in the optimization of assay performance can be extended to the measurement of other drugs in biomatrices.",
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T1 - Simple and sensitive assay for quantification of oseltamivir and its active metabolite oseltamivir carboxylate in human plasma using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry

T2 - Improved applicability to pharmacokinetic study

AU - Hu, Zhe Yi

AU - Laizure, Steven

AU - Meibohm, Bernd

AU - Herring, Vanessa L.

AU - Parker, Robert

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N2 - Although liquid chromatography/electrospray ionization tandem mass spectrometry-based assays have been reported for the measurement of the antiviral oseltamivir (OS) in human samples, these assays either involve complicated sample pretreatment or lack sensitivity. Here we introduce a straightforward approach to improve the assay performance for OS and its metabolite oseltamivir carboxylate (OSC) in human plasma. A very low concentration of mobile phase modifier can improve the ionization efficiency of both analytes, thus enabling a high sensitivity without any matrix effect. The fast LC gradient further increases the sensitivity by narrowing the peak width (6-9. s) and eluting the analytes at higher organic content. The increased ionization efficiency and minimized matrix effects enabled us to introduce a one-step protein precipitation for sample clean-up without compromising the sensitivity. The lower limit of quantification was 0.34. ng/mL for both analytes, which was at least 3 times more sensitive than published assays that involve complicated sample pretreatment. The assay involves measurement of analytes and their stable-isotope internal standards in small-volume (30-μL) plasma. Sodium fluoride was utilized to prevent the hydrolysis of OS during and after sampling. The calibration curve was linear over the range of 0.34-1000. ng/mL. Accuracy was 95-110% and the precision was 2.2-11.0%. This method was applied successfully to the human pharmacokinetic study of OS, and can estimate the relevant pharmacokinetic parameters of OS with more accuracy. The approach utilized in the optimization of assay performance can be extended to the measurement of other drugs in biomatrices.

AB - Although liquid chromatography/electrospray ionization tandem mass spectrometry-based assays have been reported for the measurement of the antiviral oseltamivir (OS) in human samples, these assays either involve complicated sample pretreatment or lack sensitivity. Here we introduce a straightforward approach to improve the assay performance for OS and its metabolite oseltamivir carboxylate (OSC) in human plasma. A very low concentration of mobile phase modifier can improve the ionization efficiency of both analytes, thus enabling a high sensitivity without any matrix effect. The fast LC gradient further increases the sensitivity by narrowing the peak width (6-9. s) and eluting the analytes at higher organic content. The increased ionization efficiency and minimized matrix effects enabled us to introduce a one-step protein precipitation for sample clean-up without compromising the sensitivity. The lower limit of quantification was 0.34. ng/mL for both analytes, which was at least 3 times more sensitive than published assays that involve complicated sample pretreatment. The assay involves measurement of analytes and their stable-isotope internal standards in small-volume (30-μL) plasma. Sodium fluoride was utilized to prevent the hydrolysis of OS during and after sampling. The calibration curve was linear over the range of 0.34-1000. ng/mL. Accuracy was 95-110% and the precision was 2.2-11.0%. This method was applied successfully to the human pharmacokinetic study of OS, and can estimate the relevant pharmacokinetic parameters of OS with more accuracy. The approach utilized in the optimization of assay performance can be extended to the measurement of other drugs in biomatrices.

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