Online solid phase extraction with liquid chromatography–tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples

Stevens, Jasper; Berg, Dirk–Jan van den; Ridder, Sanne de; Niederländer, H.A.G.; Graaf, Piet H. van der; Danhof, Meindert; Lange, Elizabeth C. M. de

doi:10.1016/j.jchromb.2010.02.024

Cited by 17 publications

(16 citation statements)

References 17 publications

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“…As a consequence, the AUC brain ECF /AUC plasma ratio value after IN administration was higher compared with IV administration (Table 1). This indicates direct nose-to-brain transport (van den Berg et al, 2004). Doubling of the dose (4 to 8 to 16 mg/kg) resulted in a doubling of the mean AUC plasma and AUC brainECF in both IV and IN studies (Table 1), indicating linear BBB distribution.…”

Section: Resultsmentioning

confidence: 85%

“…3). The resulting increase of AUC brain ECF /AUC plasma for IN administration compared with IV administration (Table 1) suggests direct nose-to-brain transport (van den Berg et al, 2004). For remoxipride, it seems that a fast onset of action can be reached by the fast systemic uptake, whereas the slower direct nose-to-brain transport is expected to result in a prolonged duration of effect after intranasal administration.…”

Section: Discussionmentioning

confidence: 99%

“…Analytical methods for the quantitation of remoxipride in small plasma and brain microdialysate samples have been previously reported (Stevens et al, 2010). In short, for the measurements of remoxipride concentrations in plasma, online solid-phase extraction was followed by highpressure liquid chromatography-tandem mass spectrometry (Finnigan TSQ Quantum Ultra Mass Spectrometer System; Thermo Fisher Scientific, Breda, The Netherlands).…”

Section: Methodsmentioning

confidence: 99%

“…However, although CSF/ plasma AUC ratios reflect differences in exposure after IN administration (van den Berg et al, 2004), they do not allow the distinction between direct nose-to-brain transport and systemic uptake in terms of absorption rate and bioavailability. Consequently, the existence of a direct nose-to-brain route is still a matter of debate (Dhuria et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Systemic and Direct Nose-to-Brain Transport Pharmacokinetic Model for Remoxipride after Intravenous and Intranasal Administration

Stevens¹,

Ploeger²,

Graaf³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Intranasal (IN) administration could be an attractive mode of delivery for drugs targeting the central nervous system, potentially providing a high bioavailability because of avoidance of a hepatic first-pass effect and rapid onset of action. However, controversy remains whether a direct transport route from the nasal cavity into the brain exists. Pharmacokinetic modeling is proposed to identify the existence of direct nose-to-brain transport in a quantitative manner. The selective dopamine-D2 receptor antagonist remoxipride was administered at different dosages, in freely moving rats, by the IN and intravenous (IV) route. Plasma and brain extracellular fluid (ECF) concentration-time profiles were obtained and simultaneously analyzed using nonlinear mixed-effects modeling. Brain ECF/plasma area under the curve ratios were 0.28 and 0.19 after IN and IV administration, respectively. A multicompartment pharmacokinetic model with two absorption compartments (noseto-systemic and nose-to-brain) was found to best describe the observed pharmacokinetic data. Absorption was described in terms of bioavailability and rate. Total bioavailability after IN administration was 89%, of which 75% was attributed to direct nose-to brain transport. Direct nose-to-brain absorption rate was slow, explaining prolonged brain ECF exposure after IN compared with IV administration. These studies explicitly provide separation and quantitation of systemic and direct nose-to-brain transport after IN administration of remoxipride in the rat. Describing remoxipride pharmacokinetics at the target site (brain ECF) in a semiphysiology-based manner would allow for better prediction of pharmacodynamic effects.

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Section: Resultsmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Systemic and Direct Nose-to-Brain Transport Pharmacokinetic Model for Remoxipride after Intravenous and Intranasal Administration

Stevens¹,

Ploeger²,

Graaf³

et al. 2011

Drug Metab Dispos

Self Cite

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show abstract

“…It is possible to continuously and simultaneously sample from multiple sites by implanting more than one probe in the same animal [5]. Microdialysis sampling coupled to an appropriate analytical technique can be used to study the target site pharmacokinetics and metabolism [6,7]. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a sensitive analytical technique that can be used to detect microdialysis samples.…”

Section: Introductionmentioning

confidence: 99%

Determination of the penetration of 9-fluoropropyl-(+)-dihydrotetrabenazine across the blood–brain barrier in rats by microdialysis combined with liquid chromatography–tandem mass spectrometry

Zhou

Qiao

Yin

et al. 2011

Journal of Chromatography B

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Current literature in mass spectrometry

2010

J. Mass Spectrom.

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Online solid phase extraction with liquid chromatography–tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples

Cited by 17 publications

References 17 publications

Systemic and Direct Nose-to-Brain Transport Pharmacokinetic Model for Remoxipride after Intravenous and Intranasal Administration

Systemic and Direct Nose-to-Brain Transport Pharmacokinetic Model for Remoxipride after Intravenous and Intranasal Administration

Determination of the penetration of 9-fluoropropyl-(+)-dihydrotetrabenazine across the blood–brain barrier in rats by microdialysis combined with liquid chromatography–tandem mass spectrometry

Current literature in mass spectrometry

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