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| Description
| - Boldine belongs to the group of aporphine alkaloids isolated from Boldo tree. In contrast with numerous reports on the pharmacological effects of boldine, the data about its pharmacokinetics and biotransformation are scarce. No validated bioanalytical method of sufficient sensitivity has so far been described in the literature which could be used for quantification of boldine in various body fluids collected in pharmacokinetic studies. This work presents, for the first time, the assay for boldine in the plasma, bile and urine of rats. It includes liquid-liquid extraction/back-extraction of boldine, its chromatographic separation and sensitive fluorescence detection. Separation was carried out on a pentafluorophenyl core-shell column (Kinetex PFP, 150 x 3 mm, 2.6 μm) in gradient elution mode with solvent system consisting of an acetonitrile-ammonium formate buffer (5 mM, pH = 3.8). Fluorimetric detection (λEX = 320 nm, λEM = 370 nm) was used for quantitative work. Validation according to the EMEA guideline proved the assay LLOQ (0.1 μmol.LMINUS SIGN 1), linearity over a broad range of 0.1-50 μmol.LMINUS SIGN 1, precision (intra- and inter-day CVs less than 4.5% and 6.1%, respectively) and accuracy (relative errors between MINUS SIGN 5.8% and 4.8%). In a pilot pharmacokinetic experiment, the concentration-time profiles were described for boldine (single i.v. bolus 50 mg.kg(MINUS SIGN 1) in plasma and bile and cumulative excretion in urine was investigated. The major metabolites identified by means of LC-MSn were boldine-O-glucuronide, boldine-O-sulphate and disulphate, boldine-O-glucuronide-O-sulphate and N-demethyl-boldine-O-sulphate.
- Boldine belongs to the group of aporphine alkaloids isolated from Boldo tree. In contrast with numerous reports on the pharmacological effects of boldine, the data about its pharmacokinetics and biotransformation are scarce. No validated bioanalytical method of sufficient sensitivity has so far been described in the literature which could be used for quantification of boldine in various body fluids collected in pharmacokinetic studies. This work presents, for the first time, the assay for boldine in the plasma, bile and urine of rats. It includes liquid-liquid extraction/back-extraction of boldine, its chromatographic separation and sensitive fluorescence detection. Separation was carried out on a pentafluorophenyl core-shell column (Kinetex PFP, 150 x 3 mm, 2.6 μm) in gradient elution mode with solvent system consisting of an acetonitrile-ammonium formate buffer (5 mM, pH = 3.8). Fluorimetric detection (λEX = 320 nm, λEM = 370 nm) was used for quantitative work. Validation according to the EMEA guideline proved the assay LLOQ (0.1 μmol.LMINUS SIGN 1), linearity over a broad range of 0.1-50 μmol.LMINUS SIGN 1, precision (intra- and inter-day CVs less than 4.5% and 6.1%, respectively) and accuracy (relative errors between MINUS SIGN 5.8% and 4.8%). In a pilot pharmacokinetic experiment, the concentration-time profiles were described for boldine (single i.v. bolus 50 mg.kg(MINUS SIGN 1) in plasma and bile and cumulative excretion in urine was investigated. The major metabolites identified by means of LC-MSn were boldine-O-glucuronide, boldine-O-sulphate and disulphate, boldine-O-glucuronide-O-sulphate and N-demethyl-boldine-O-sulphate. (en)
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| Title
| - Development of an HPLC fluorescence method for determination of boldine in plasma, bile and urine of rats and identification of its major metabolites by LC-MS/MS
- Development of an HPLC fluorescence method for determination of boldine in plasma, bile and urine of rats and identification of its major metabolites by LC-MS/MS (en)
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| skos:prefLabel
| - Development of an HPLC fluorescence method for determination of boldine in plasma, bile and urine of rats and identification of its major metabolites by LC-MS/MS
- Development of an HPLC fluorescence method for determination of boldine in plasma, bile and urine of rats and identification of its major metabolites by LC-MS/MS (en)
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| skos:notation
| - RIV/00216208:11150/13:10140008!RIV14-MZ0-11150___
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
| - I, P(EE2.3.30.0022), P(NT13473)
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/00216208:11150/13:10140008
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - Fluorescence; Core-shell column; LC/MS/MS; Pharmacokinetics; Metabolites; Boldine (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
| - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
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| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...vavai/riv/projekt
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| http://linked.open...UplatneniVysledku
| |
| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Chládek, Jaroslav
- Mičuda, Stanislav
- Tomšík, Pavel
- Hroch, Miloš
- Cermanová, Jolana
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| http://linked.open...ain/vavai/riv/wos
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| issn
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| number of pages
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| http://bibframe.org/vocab/doi
| - 10.1016/j.jchromb.2013.07.009
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| http://localhost/t...ganizacniJednotka
| |
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