Simultaneous measurement of heroin and its metabolites in brain extracellular fluid by microdialysis and ultra performance liquid chromatography tandem mass spectrometry

Journal of Pharmacological and Toxicological Methods
A GottasJ Morland

Abstract

The pharmacokinetic profile and systemic bioavailability of a substance is often described by blood or total tissue concentrations. For centrally acting drugs, like opioids, the free fraction of active compound in brain extracellular fluid (ECF) is more likely to be correlated to the pharmacodynamic effects than the blood concentrations. Drugs of abuse, like heroin, are often administered intravenously as bolus injections, and the blood concentrations might change rapidly due to metabolism and distribution. The aim of our study was to establish a method to measure the free fraction of heroin and its metabolites in brain ECF, and follow their fast changes in concentration. Sprague-Dawley rats were injected intravenously with a bolus of heroin. Heroin and its main metabolites 6-monoacetylmorphine, morphine and morphine-3-glucuronide were measured simultaneously. Brain microdialysis was used for sampling and a method for quantification using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. Deuterated analogues for each analyte were included in the microdialysis perfusion solution as calibrators for recovery estimation. A highly sensitive UPLC-MS/MS method allowed short sampling intervals...Continue Reading

References

Jul 1, 1992·The Journal of Pharmacy and Pharmacology·D A BarrettP N Shaw
Jan 1, 1987·American Indian and Alaska Native Mental Health Research : the Journal of the National Center·R Peters
Sep 4, 1999·Clinical and Experimental Pharmacology & Physiology·A Y SalmonH Soreq
Dec 8, 2000·Advanced Drug Delivery Reviews·E C de LangeD D Breimer
Sep 6, 2002·Pharmacology, Biochemistry, and Behavior·Marte HandalJørg Mørland
Apr 28, 2005·Current Drug Metabolism·M J Cano-CebriánL Granero
Nov 9, 2007·Journal of Pharmaceutical Sciences·Jörgen BengtssonMargareta Hammarlund-Udenaes
Aug 1, 2008·Current Clinical Pharmacology·Elisabeth J RookJos H Beijnen
Nov 21, 2008·Journal of Pharmaceutical and Biomedical Analysis·Ralph Nii Okai Tettey-Amlalo, Isadore Kanfer
Jun 23, 2009·The Journal of Pharmacology and Experimental Therapeutics·Jannike Mørch AndersenJørg Mørland
Jul 8, 2010·Journal of Pharmaceutical and Biomedical Analysis·Gillian Whitaker, Craig E Lunte

❮ Previous
Next ❯

Citations

Sep 30, 2014·Peptides·Richard J Bodnar
Sep 24, 2016·Forensic Toxicology·André GottåsGudrun Høiseth
May 15, 2015·Pharmaceutical Research·Robert GharaviHazem E Hassan
Mar 1, 2014·The International Journal of Neuropsychopharmacology·A GottåsJ Mørland
Oct 18, 2016·Journal of Mass Spectrometry : JMS·Laszlo ProkaiMichael J Forster
Feb 23, 2019·Addiction Biology·Anne Marte Sjursen KvelloInger Lise Bogen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.