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

Gottås, André; Øiestad, Elisabeth Leere; Boix, Fernando; Ripel, Åse; Thaulow, Cecilie Hasselø; Pettersen, B; Vindenes, Vigdis; Mørland, Jörg

doi:10.1016/j.vascn.2012.04.009

Cited by 20 publications

(26 citation statements)

References 31 publications

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“…A 2-min interval was applied when studying heroin and its metabolites 6-acetylmorphine and morphine in rats, giving a very high time resolution of the pharmacokinetics of brain uptake of the compounds in relation to pharmacological effect (88,89).…”

Section: Trade-offs When Designing a Microdialysis Studymentioning

confidence: 99%

Microdialysis as an Important Technique in Systems Pharmacology—a Historical and Methodological Review

Hammarlund‐Udenaes

2017

AAPS J

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Abstract.Microdialysis has contributed with very important knowledge to the understanding of target-specific concentrations and their relationship to pharmacodynamic effects from a systems pharmacology perspective, aiding in the global understanding of drug effects. This review focuses on the historical development of microdialysis as a method to quantify the pharmacologically very important unbound tissue concentrations and of recent findings relating to modeling microdialysis data to extrapolate from rodents to humans, understanding distribution of drugs in different tissues and disease conditions. Quantitative microdialysis developed very rapidly during the early 1990s. Method development was in focus in the early years including development of quantitative microdialysis, to be able to estimate true extracellular concentrations. Microdialysis has significantly contributed to the understanding of active transport at the blood-brain barrier and in other organs. Examples are presented where microdialysis together with modeling has increased the knowledge on tissue distribution between species, in overweight patients and in tumors, and in metabolite contribution to drug effects. More integrated metabolomic studies are still sparse within the microdialysis field, although a great potential for tissue and disease-specific measurements is evident.

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Section: Trade-offs When Designing a Microdialysis Studymentioning

confidence: 99%

Microdialysis as an Important Technique in Systems Pharmacology—a Historical and Methodological Review

Hammarlund‐Udenaes

2017

AAPS J

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“…. Further improvement of the method may include the application of ultra‐performance liquid chromatograph (UPLC), which has been reported to reduce an assay's cycle time to 1 min upon measuring heroin and its metabolite from the extracellular fluid of the rat brain using in vivo microdialysis sampling …”

Section: Resultsmentioning

confidence: 99%

Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates

et al. 2016

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We report the evaluation of several mass spectrometry-based methods for the determination of carisoprodol and meprobamate in samples obtained from the rat brain by in vivo intracranial microdialyis. Among the techniques that aspire to perform analyses without chromatographic separation and thereby increase throughput, chip-based nanoelectrospray ionization and the use of an atmospheric pressure solids analysis probe fell short of requirements because of insufficient detection sensitivity and hard ionization, respectively. Although direct analysis in real time (DART) provided the required soft ionization, shortcomings of a tandem mass spectrometry-based assay also included inadequate detection sensitivity and, in addition, poor quantitative reproducibility. Therefore, liquid chromatography coupled with atmospheric-pressure chemical ionization tandem mass spectrometry was developed to determine carisoprodol and meprobamate from artificial cerebrospinal fluid as the medium. No desalting and/or extraction of the samples were necessary. The assay, combined with in vivo sampling via intracranial microdialyis, afforded time-resolved concentration profiles for the drug and its major metabolite from the nucleus accumbens region of the brain in rats after systemic administration of carisoprodol.

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“…Despite its highly addictive properties, diacetylmorphine exhibits a low-binding affinity and efficacy at μ-opioid receptors (185). Thus, it has been proposed that diacetylmorphine behaves primarily as highly lipophilic prodrug, able to cross the BBB (186) and then be subsequently converted to active metabolites with high μ-opioid receptor affinities (187). Diacetlymorphine is rapidly deacetylated to its more active metabolites 6-monoacetylmorphine (6-MAM) and then morphine within 10 min of administration (188,189).…”

Section: Diacetylmorphinementioning

confidence: 99%

Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

et al. 2015

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Opioid-related deaths, abuse, and drug interactions are growing epidemic problems that have medical, social, and economic implications. Drug transporters play a major role in the disposition of many drugs, including opioids; hence they can modulate their pharmacokinetics, pharmacodynamics and their associated drug-drug interactions (DDIs). Our understanding of the interaction of transporters with many therapeutic agents is improving; however, investigating such interactions with opioids is progressing relatively slowly despite the alarming number of opioids-mediated DDIs that may be related to transporters. This review presents a comprehensive report of the current literature relating to opioids and their drug transporter interactions. Additionally, it highlights the emergence of transporters that are yet to be fully identified but may play prominent roles in the disposition of opioids, the growing interest in transporter genomics for opioids, and the potential implications of opioid-drug transporter interactions for cancer treatments. A better understanding of drug transporters interactions with opioids will provide greater insight into potential clinical DDIs and could help improve opioids safety and efficacy.

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

Cited by 20 publications

References 31 publications

Microdialysis as an Important Technique in Systems Pharmacology—a Historical and Methodological Review

Microdialysis as an Important Technique in Systems Pharmacology—a Historical and Methodological Review

Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates

Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

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