The effective concentration of a drug in the blood, i.e. the concentration of a free drug in the blood, is influenced by the strength of drug binding onto plasma proteins. Besides its efficacy, these interactions subsequently influence the liberation, absorption, distribution, metabolism, excretion, and toxicological properties of the drug. It is important to not only determine the binding strength and stoichiometry, but also the binding site of a drug on the plasma protein molecule, because the co-administration of drugs with the same binding site can affect the above-mentioned concentration and as a result the pharmacological behavior of the drugs and lead to side effects caused by the change in free drug concentration, its toxicity. In this study, the binding characteristics of six drugs with human serum albumin, the most abundant protein in human plasma, were determined by capillary electrophoresis-frontal analysis, and the obtained values of binding parameters were compared with the literature data. The effect of several drugs and site markers on the binding of l-tryptophan and lidocaine to human serum albumin was investigated in subsequent displacement studies which thus demonstrated the usability of capillary electrophoresis as an automated high-throughput screening method for drug-protein binding studies.
- Klíčová slova
- binding constant, binding sites, capillary electrophoresis-frontal analysis, drug competition, human serum albumin,
- MeSH
- chlorpropamid analýza farmakologie MeSH
- diklofenak analýza farmakologie MeSH
- elektroforéza kapilární MeSH
- fenylbutazon analýza farmakologie MeSH
- flurbiprofen analýza farmakologie MeSH
- ibuprofen analýza farmakologie MeSH
- lidé MeSH
- lidokain antagonisté a inhibitory chemie MeSH
- lidský sérový albumin chemie MeSH
- tolbutamid analýza farmakologie MeSH
- tryptofan antagonisté a inhibitory chemie MeSH
- vazebná místa účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chlorpropamid MeSH
- diklofenak MeSH
- fenylbutazon MeSH
- flurbiprofen MeSH
- ibuprofen MeSH
- lidokain MeSH
- lidský sérový albumin MeSH
- tolbutamid MeSH
- tryptofan MeSH
Unknown impurities were identified in ibuprofen (IBU) soft gelatin capsules (SGCs) during long-term stability testing by a UHPLC method with UV detection and its chemical formula was determined using high resolution/accurate mass (HRAM) LC-MS. Reference standards of the impurities were subsequently synthesized, isolated by semi-preparative HPLC and characterized using HRAM LC-MS, NMR and IR. Two impurities were formed by esterification of IBU with polyethylene glycol (PEG), which is used as a fill of the SGCs, and were identified as IBU-PEG monoester and IBU-PEG diester. Two other degradants arised from reaction of IBU with sorbitol and sorbitan, which are components of the shell and serves as plasticizers. Thus, IBU sorbitol monoester (IBU-sorbitol) and IBU sorbitan monoester (IBU-sorbitan ester) were identified. An UHPLC method was further optimized in order to separate, selectively detect and quantify the degradation products in IBU SGCs.
- MeSH
- esterifikace MeSH
- ibuprofen analýza chemie izolace a purifikace MeSH
- polysorbáty MeSH
- referenční standardy MeSH
- sorbitol MeSH
- stabilita léku MeSH
- tobolky MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- želatina MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ibuprofen MeSH
- polysorbáty MeSH
- sorbitol MeSH
- tobolky MeSH
- želatina MeSH
Non-steroidal anti-inflammatory drugs (NSAIDs) belong to most used pharmaceuticals in the human and veterinary medicine. The widespread consumption of NSAIDs has led to their ubiquitous occurrence in water environment including large river systems. In the present study, concentrations of the five most frequently used NSAIDs (ibuprofen, diclofenac, naproxen, ketoprofen and indomethacin) were determined in the watercourses of the river Elbe basin in Czech Republic. The presence of the pharmaceuticals was measured at 29 sampling sites including urban and rural areas, small creeks and main tributaries of the Elbe monthly from April to December of 2011. For the NSAIDs quantitation, the comprehensive analytical method combing pentafluorobenzyl bromide (PFBBr) derivatization with highly sensitive two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-TOFMS) was developed. Although the content of all NSAIDs varied at the particular sampling points significantly, total amount of particular compounds was relatively stable during all monitored periods with only non-significant increase in the spring and autumnal months. Ibuprofen was found to be the most abundant drug with maximum concentration of 3210 ng/L, followed by naproxen, diclofenac and ketoprofen (1423.8 ng/L, 1080 ng/L and 929.8 ng/L, respectively). Indomethacin was found only at several sampling sites (maximum concentration of 69.3 ng/L). Concentrations of all compounds except ibuprofen were significantly higher at sampling sites with low flow rates (creeks), followed by the biggest watercourses.
- Klíčová slova
- Czech Republic, Elbe basin, GCxGC-TOFMS, NSAID, Pharmaceuticals, Surface water,
- MeSH
- antiflogistika nesteroidní analýza MeSH
- chemické látky znečišťující vodu analýza MeSH
- diklofenak analýza MeSH
- ibuprofen analýza MeSH
- indomethacin analýza MeSH
- ketoprofen analýza MeSH
- monitorování životního prostředí MeSH
- naproxen analýza MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí metody MeSH
- řeky chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- chemické látky znečišťující vodu MeSH
- diklofenak MeSH
- ibuprofen MeSH
- indomethacin MeSH
- ketoprofen MeSH
- naproxen MeSH
The uptake and metabolism of ibuprofen (IBU) by plants at the cellular level was investigated using a suspension culture of A. thaliana. Almost all IBU added to the medium (200 μM) was metabolized or bound to insoluble structures in 5 days. More than 300 metabolites were determined by liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis, and most of these are first reported for plants here. Although hydroxylated derivatives formed by oxidation on the isobutyl side chain were the main first-step products of IBU degradation, conjugates of these products with sugar, methyl and amino acid groups were the dominant metabolites in the culture. The main portion of total added IBU (81%) was accumulated in the extractable intracellular pool, whereas the cultivation medium fraction contained only 19%. The amount of the insoluble cell-wall-bound IBU was negligible (0.005% of total IBU).
- Klíčová slova
- Arabidopsis thaliana, Ibuprofen, Metabolism, Plant cells, Sequestration,
- MeSH
- antiflogistika nesteroidní metabolismus MeSH
- Arabidopsis metabolismus MeSH
- hmotnostní spektrometrie MeSH
- hydroxylace MeSH
- ibuprofen analýza metabolismus MeSH
- rostliny metabolismus MeSH
- suspenze MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- ibuprofen MeSH
- suspenze MeSH
The possibilities of reaching higher sensitivity in capillary electrophoretic analyses of complex samples with ESI-MS detection were investigated on the example of analysis of diclofenac and ibuprofen in waters. The applied separation approach is based on application of isotachophoresis that ensures permanent stacking of analytes until they reach the detector. Investigation of the possibilities of MS detector optimization have shown that optimization of fragmentor voltage and working in the SIM mode with collection of data for multiple fragments both increases the method specificity and approx. doubles its sensitivity. Combination with an offline SPE preconcentration step resulted in very high sensitivity of the described methodology with a reached LOD below 2 × 10(-12) M, corresponding to analyte levels of 0.6 ng L(-1) of diclofenac and 0.4 ng L(-1) of ibuprofen. The results demonstrate that CE-MS, particularly when performed in the ITP mode, has the potential to reach sensitivities comparable to HPLC-MS.
- Klíčová slova
- Diclofenac, Ibuprofen, Isotachophoresis, Mass spectrometric detection, Solid phase extraction, Water analysis,
- MeSH
- antiflogistika nesteroidní analýza MeSH
- chemické látky znečišťující vodu analýza MeSH
- diklofenak analýza MeSH
- extrakce na pevné fázi MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- ibuprofen analýza MeSH
- izotachoforéza metody MeSH
- limita detekce MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- chemické látky znečišťující vodu MeSH
- diklofenak MeSH
- ibuprofen MeSH
We introduce an easy but highly descriptive model of separation efficiency of dual-selector systems in capillary electrophoresis. The model expresses effective mobilities of analytes in dual-selector mixtures as a function of mixture composition and total concentration. The effective mobility follows the pattern familiar from single-selector systems, while complexation constant and mobility of the complex are replaced by the same but "overall" parameters and a total concentration of the mixture takes the role of a selector concentration. The overall parameters can be either calculated from the individual ones (an arbitrary mixture) or measured directly (a particular mixture). We inspected two model dual-selector systems consisting of heptakis(2,6-di-O-methyl)-β-CD and β-CD and of heptakis(2,6-di-O-methyl)-β-CD and 6-O-α-maltosyl-β-CD, and ibuprofen and flurbiprofen as model analytes (pH 8.2, non-enantioselective separation). Adopting any optimization strategy typically used in single-selector systems and finding an optimal mixture composition and total concentration is perhaps the prime benefit of the model. We demonstrate this approach on the selectivity parameter and show that the model is precise enough to be used in analytical practice. It also results that an electromigration order (reversal) of analytes can exhibit a rather curious dependency on the mixture composition and concentration. Last, the model can be used for better understanding of separation principles in dual-selector systems in general.
- Klíčová slova
- Capillary zone electrophoresis, Complexation, Dual selector system, Model of electromigration,
- MeSH
- elektroforéza kapilární metody MeSH
- flurbiprofen analýza MeSH
- ibuprofen analýza MeSH
- stereoizomerie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- flurbiprofen MeSH
- ibuprofen MeSH
The subject of this work is the definition of a simple model based on general ITP theory that allows describing and predicting the behavior of ITP systems compatible with ESI-MS detection. The model is exemplified by anionic ITP of weak acids that represent an interesting potential application field of ITP-ESI-MS. Suitable ESI-compatible electrolyte systems of very simple composition are proposed including a special free-acid ITP arrangement. The properties of these systems are discussed using illustrative diagrams of their stacking windows. The use of anionic ITP-ESI-MS in negative-ion ESI mode is reported for the first time and its suitability for sensitive trace analysis is demonstrated. The presented ITP-ESI-MS application example comprises a free-acid ITP system formed of formic and propionic acids and direct injection analysis of ibuprofen and diclofenac in waters with quantitation limits of the order 10(-10) M.
- Klíčová slova
- Diclofenac, ESI-MS detection, Ibuprofen, Isotachophoresis, Water analysis,
- MeSH
- anionty chemie MeSH
- antiflogistika nesteroidní analýza MeSH
- diklofenak analýza MeSH
- elektroforéza kapilární MeSH
- elektrolyty chemie MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- ibuprofen analýza MeSH
- izotachoforéza metody MeSH
- kyseliny chemie MeSH
- limita detekce MeSH
- neopioidní analgetika analýza MeSH
- pitná voda analýza MeSH
- řeky chemie MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- anionty MeSH
- antiflogistika nesteroidní MeSH
- diklofenak MeSH
- elektrolyty MeSH
- ibuprofen MeSH
- kyseliny MeSH
- neopioidní analgetika MeSH
- pitná voda MeSH
Capillary zone electrophoresis with spectrophotometric detection was used for the determination of ibuprofen (IB) and flurbiprofen (FL) in pharmaceuticals. The separation was carried out in a fused silica capillary (60 cm x 100 microm i.d. effective length 45 cm) at 30 kV with UV detection at 232 nm. The optimized background electrolyte was 20mM N-(2-acetamido)-2-aminoethanesulfonic acid (ACES) with 20mM imidazole and 10mM alpha-cyclodextrin of pH 7.3. 2-Naphthoxyacetic acid was used as internal standard. A single analysis took less than 5 min. Rectilinear calibration ranges were 2-500 mg l(-1) for IB and 1-60 mg l(-1) for FL. The relative standard deviations (R.S.D.) values (n=6) were 1.53% for IB and 1.29% for FL (for 200 mg l(-1) IB and 10 mg l(-1) FL). This validated method has been successfully applied for the routine analysis of 10 commercially available pharmaceutical preparations (syrup, tablets, cream and gel).
- MeSH
- antiflogistika nesteroidní analýza MeSH
- elektroforéza kapilární metody MeSH
- flurbiprofen analýza MeSH
- ibuprofen analýza MeSH
- léčivé přípravky analýza MeSH
- reprodukovatelnost výsledků MeSH
- stereoizomerie MeSH
- tablety MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- flurbiprofen MeSH
- ibuprofen MeSH
- léčivé přípravky MeSH
- tablety MeSH
- MeSH
- baklofen analýza MeSH
- chloridy analýza MeSH
- ibuprofen analýza MeSH
- imidazoly analýza MeSH
- ketokonazol MeSH
- léčivé přípravky analýza MeSH
- piperaziny analýza MeSH
- rozpouštědla MeSH
- salicylany analýza MeSH
- spektrofotometrie ultrafialová * MeSH
- terbutalin analýza MeSH
- xipamid analýza MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- baklofen MeSH
- chloridy MeSH
- ibuprofen MeSH
- imidazoly MeSH
- ketokonazol MeSH
- léčivé přípravky MeSH
- piperaziny MeSH
- rozpouštědla MeSH
- salicylany MeSH
- terbutalin MeSH
- xipamid MeSH
