Transdermal reverse iontophoresis of valproate: a non-invasive method for therapeutic drug monitoring

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Abstract

Purpose. The objectives of this work were (a) to explore the potential of transdermal reverse iontophoresis for therapeutic drug monitoring and (b) to develop an internal standard calibration procedure so as to render the technique completely noninvasive. Methods. A series of in vitro iontophoresis experiments was performed in which the subdermal concentration of sodium valproate was varied from 21 M to 1 mM. Glutamic acid was also introduced into the subdermal donor at a fixed concentration to act as an internal standard for the calibration method. Results. Both valproate and glutamate anions were recovered, as expected, at the anodal receptor chamber. The iontophoretic extraction flux of valproate was linearly correlated with the subdermal concentration. Glutamate flux was constant. It follows that the ratio of extracted fluxes (valproate/glutamate) was directly dependent upon (a) the subdermal valproate concentration and (b) the subdermal concentration ratio (valproate/glutamate), offering a means, thereby, to a completely noninvasive methodology. Conclusions. This work demonstrates the potential of reverse iontophoresis for noninvasive therapeutic monitoring. The simultaneous quantification of the analyte of interest and of an internal standard renders the withdrawal of a blood sample unnecessary.
Original languageEnglish
Pages (from-to)1508-1513
Number of pages6
JournalPharmaceutical Research
Volume20
Issue number9
DOIs
Publication statusPublished - 2003

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Iontophoresis
Drug Monitoring
Valproic Acid
Glutamic Acid
Monitoring
Pharmaceutical Preparations
Fluxes
Calibration
Anions
Blood

Cite this

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title = "Transdermal reverse iontophoresis of valproate: a non-invasive method for therapeutic drug monitoring",
abstract = "Purpose. The objectives of this work were (a) to explore the potential of transdermal reverse iontophoresis for therapeutic drug monitoring and (b) to develop an internal standard calibration procedure so as to render the technique completely noninvasive. Methods. A series of in vitro iontophoresis experiments was performed in which the subdermal concentration of sodium valproate was varied from 21 M to 1 mM. Glutamic acid was also introduced into the subdermal donor at a fixed concentration to act as an internal standard for the calibration method. Results. Both valproate and glutamate anions were recovered, as expected, at the anodal receptor chamber. The iontophoretic extraction flux of valproate was linearly correlated with the subdermal concentration. Glutamate flux was constant. It follows that the ratio of extracted fluxes (valproate/glutamate) was directly dependent upon (a) the subdermal valproate concentration and (b) the subdermal concentration ratio (valproate/glutamate), offering a means, thereby, to a completely noninvasive methodology. Conclusions. This work demonstrates the potential of reverse iontophoresis for noninvasive therapeutic monitoring. The simultaneous quantification of the analyte of interest and of an internal standard renders the withdrawal of a blood sample unnecessary.",
author = "Delgado-Charro, {M B} and Guy, {R H}",
year = "2003",
doi = "10.1023/A:1025730815971",
language = "English",
volume = "20",
pages = "1508--1513",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "9",

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TY - JOUR

T1 - Transdermal reverse iontophoresis of valproate: a non-invasive method for therapeutic drug monitoring

AU - Delgado-Charro, M B

AU - Guy, R H

PY - 2003

Y1 - 2003

N2 - Purpose. The objectives of this work were (a) to explore the potential of transdermal reverse iontophoresis for therapeutic drug monitoring and (b) to develop an internal standard calibration procedure so as to render the technique completely noninvasive. Methods. A series of in vitro iontophoresis experiments was performed in which the subdermal concentration of sodium valproate was varied from 21 M to 1 mM. Glutamic acid was also introduced into the subdermal donor at a fixed concentration to act as an internal standard for the calibration method. Results. Both valproate and glutamate anions were recovered, as expected, at the anodal receptor chamber. The iontophoretic extraction flux of valproate was linearly correlated with the subdermal concentration. Glutamate flux was constant. It follows that the ratio of extracted fluxes (valproate/glutamate) was directly dependent upon (a) the subdermal valproate concentration and (b) the subdermal concentration ratio (valproate/glutamate), offering a means, thereby, to a completely noninvasive methodology. Conclusions. This work demonstrates the potential of reverse iontophoresis for noninvasive therapeutic monitoring. The simultaneous quantification of the analyte of interest and of an internal standard renders the withdrawal of a blood sample unnecessary.

AB - Purpose. The objectives of this work were (a) to explore the potential of transdermal reverse iontophoresis for therapeutic drug monitoring and (b) to develop an internal standard calibration procedure so as to render the technique completely noninvasive. Methods. A series of in vitro iontophoresis experiments was performed in which the subdermal concentration of sodium valproate was varied from 21 M to 1 mM. Glutamic acid was also introduced into the subdermal donor at a fixed concentration to act as an internal standard for the calibration method. Results. Both valproate and glutamate anions were recovered, as expected, at the anodal receptor chamber. The iontophoretic extraction flux of valproate was linearly correlated with the subdermal concentration. Glutamate flux was constant. It follows that the ratio of extracted fluxes (valproate/glutamate) was directly dependent upon (a) the subdermal valproate concentration and (b) the subdermal concentration ratio (valproate/glutamate), offering a means, thereby, to a completely noninvasive methodology. Conclusions. This work demonstrates the potential of reverse iontophoresis for noninvasive therapeutic monitoring. The simultaneous quantification of the analyte of interest and of an internal standard renders the withdrawal of a blood sample unnecessary.

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DO - 10.1023/A:1025730815971

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SN - 0724-8741

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