Simultaneous quantification of high-dose naloxone and naloxone-3-β-D-glucuronide in human plasma by UHPLC-MS/MS

Kenneth Thermann Kongstad; Theodoros Papathanasiou; Anders Springborg; Trine Meldgaard Lund; Mads Utke Werner; Dan Stærk

doi:10.4155/bio-2018-0134

Simultaneous quantification of high-dose naloxone and naloxone-3-β-D-glucuronide in human plasma by UHPLC-MS/MS

Kenneth Thermann Kongstad, Theodoros Papathanasiou, Anders Springborg, Trine Meldgaard Lund, Mads Utke Werner, Dan Stærk

3 Citations (Scopus)

Abstract

Aim: High-dose administration of the μ-opioid receptor inverse agonist naloxone (NX), has previously been demonstrated to reinstate nocifensive behavior in the late phase of inflammatory injuries. However, no current analytical methods can provide pharmacokinetic insight into the pharmacodynamic response of high-dose administration of NX. Materials & methods: Based on protein precipitation using 50 μl human plasma, NX and naloxone-β-d-glucuronide (NXG) was analysed by UHPLC-MS/MS with 6 min cycle time. Results: A method for quantification of high-dose administered NX and NXG was developed and validated with intra- and interday precision and accuracy within ≤8.5% relative standard deviation (RSD) and -1.2-5.5% relative error (RE) for NX and ≤9.6% RSD and 0.6-6.5% RE for NXG. The method show excellent internal standard corrected matrix effects. Conclusion: A rapid UHPLC-MS/MS method was developed for quantification of NX and NXG in human plasma within 10-4000 ng/ml.

Original language	English
Journal	Bioanalysis
Volume	11
Pages (from-to)	165-173
ISSN	1757-6180
DOIs	https://doi.org/10.4155/bio-2018-0134
Publication status	Published - Feb 2019

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@article{f5d141922b144457b703cc3d578cdb96,

title = "Simultaneous quantification of high-dose naloxone and naloxone-3-β-D-glucuronide in human plasma by UHPLC-MS/MS",

abstract = "Aim: High-dose administration of the μ-opioid receptor inverse agonist naloxone (NX), has previously been demonstrated to reinstate nocifensive behavior in the late phase of inflammatory injuries. However, no current analytical methods can provide pharmacokinetic insight into the pharmacodynamic response of high-dose administration of NX. Materials & methods: Based on protein precipitation using 50 μl human plasma, NX and naloxone-β-d-glucuronide (NXG) was analysed by UHPLC-MS/MS with 6 min cycle time. Results: A method for quantification of high-dose administered NX and NXG was developed and validated with intra- and interday precision and accuracy within ≤8.5% relative standard deviation (RSD) and -1.2-5.5% relative error (RE) for NX and ≤9.6% RSD and 0.6-6.5% RE for NXG. The method show excellent internal standard corrected matrix effects. Conclusion: A rapid UHPLC-MS/MS method was developed for quantification of NX and NXG in human plasma within 10-4000 ng/ml.",

author = "Kongstad, {Kenneth Thermann} and Theodoros Papathanasiou and Anders Springborg and Lund, {Trine Meldgaard} and Werner, {Mads Utke} and Dan St{\ae}rk",

year = "2019",

month = feb,

doi = "10.4155/bio-2018-0134",

language = "English",

volume = "11",

pages = "165--173",

journal = "Bioanalysis",

issn = "1757-6180",

publisher = "Future Science",

}

TY - JOUR

T1 - Simultaneous quantification of high-dose naloxone and naloxone-3-β-D-glucuronide in human plasma by UHPLC-MS/MS

AU - Kongstad, Kenneth Thermann

AU - Papathanasiou, Theodoros

AU - Springborg, Anders

AU - Lund, Trine Meldgaard

AU - Werner, Mads Utke

AU - Stærk, Dan

PY - 2019/2

Y1 - 2019/2

N2 - Aim: High-dose administration of the μ-opioid receptor inverse agonist naloxone (NX), has previously been demonstrated to reinstate nocifensive behavior in the late phase of inflammatory injuries. However, no current analytical methods can provide pharmacokinetic insight into the pharmacodynamic response of high-dose administration of NX. Materials & methods: Based on protein precipitation using 50 μl human plasma, NX and naloxone-β-d-glucuronide (NXG) was analysed by UHPLC-MS/MS with 6 min cycle time. Results: A method for quantification of high-dose administered NX and NXG was developed and validated with intra- and interday precision and accuracy within ≤8.5% relative standard deviation (RSD) and -1.2-5.5% relative error (RE) for NX and ≤9.6% RSD and 0.6-6.5% RE for NXG. The method show excellent internal standard corrected matrix effects. Conclusion: A rapid UHPLC-MS/MS method was developed for quantification of NX and NXG in human plasma within 10-4000 ng/ml.

AB - Aim: High-dose administration of the μ-opioid receptor inverse agonist naloxone (NX), has previously been demonstrated to reinstate nocifensive behavior in the late phase of inflammatory injuries. However, no current analytical methods can provide pharmacokinetic insight into the pharmacodynamic response of high-dose administration of NX. Materials & methods: Based on protein precipitation using 50 μl human plasma, NX and naloxone-β-d-glucuronide (NXG) was analysed by UHPLC-MS/MS with 6 min cycle time. Results: A method for quantification of high-dose administered NX and NXG was developed and validated with intra- and interday precision and accuracy within ≤8.5% relative standard deviation (RSD) and -1.2-5.5% relative error (RE) for NX and ≤9.6% RSD and 0.6-6.5% RE for NXG. The method show excellent internal standard corrected matrix effects. Conclusion: A rapid UHPLC-MS/MS method was developed for quantification of NX and NXG in human plasma within 10-4000 ng/ml.

U2 - 10.4155/bio-2018-0134

DO - 10.4155/bio-2018-0134

M3 - Journal article

C2 - 30661370

SN - 1757-6180

VL - 11

SP - 165

EP - 173

JO - Bioanalysis

JF - Bioanalysis

ER -

Simultaneous quantification of high-dose naloxone and naloxone-3-β-D-glucuronide in human plasma by UHPLC-MS/MS

Abstract

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