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Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates - PubMed

Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates

Laszlo Prokai et al. J Mass Spectrom. 2016 Oct.

Abstract

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 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 was 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. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: LC-MS/MS; atmospheric pressure chemical ionization; atmospheric pressure solids analysis probe; carisoprodol; direct analysis in real time; in vivo intracranial microdialysis; meprobamate; nanoelectrospray ionization.

Copyright © 2016 John Wiley & Sons, Ltd.

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Figures

Figure 1
Figure 1

Chip-based nanoESI, DART and ASAP mass spectra of (A) carisoprodol and (B) meprobamate.

Figure 2
Figure 2

DART-MS/MS analysis of meprobamate (3 ng, upper trace) and carisorprodol (3 ng, middle trace) in triplicate using diethyl acetamidomalonate as an ISTD (1.5 ng, lower trace). The insets indicate the SRMs and the fragmentation of [M+H]+ based on which the compound was detected (m/z given as nominal mass). Carisoprodol-to-ISTD peak area ratio: 0.075±0.032 (CV: 42.1%); meprobamate-to-ISTD peak area ratio: 0.076±0.060.96 (CV: 78.5%); carisoprodol-to-meprobamate peak area ratio: 1.525±1.360.96 (CV: 89.2%).

Figure 3
Figure 3

APCI mass spectra and CID-MS/MS product ion spectra of the [M+H]+ ions of (A) carisoprodol and (B) meprobamate.

Figure 4
Figure 4

Three replicate 5-μL injections of meprobamate (1 ng/mL, upper traces), carisoprodol (1 ng/mL, middle traces) for LC–APCI-MS/MS analysis using diethyl acetamidomalonate as ISTD (10 ng/mL, lower traces) and SRMs indicated (m/z given as nominal mass). Carisoprodol-to-ISTD peak area ratio: 1.43·10−2±1.03·10−3 (CV: 9.8%); meprobamate-to-ISTD peak area ratio: 2.60·10−2±1.89·10−3 (CV: 7.3%).

Figure 5
Figure 5

Carisoprodol and meprobamate concentrations in the extracellular fluid of the nucleus accumbens of rats determined by in vivo microdialysis followed by LC–APCI-MS/MS assay after administration of 100 mg/kg i.p. carisoprodol.

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