Jindra Valentová

Chromatographic Separation and Enantiomeric Resolution of Flurbiprofen and its Major Metabolites

SummaryThe chromatographic separation and resolution of the enantiomers of flurbiprofen and its two major metabolites, 4′-hydroxyflurbiprofen and 3′-hydroxy-4′-methoxyflurbiprofen was investigated using four different approaches: reversed-phase HPLC after pre-column derivatization with (R)-1-(naphthen-1-yl)ethylamine; reversed-phase HPLC using hydroxypropyl-β-cyclodextrin as a chiral mobile phase additive; chiral-phase HPLC using either an α1-acid glycoprotein CSP (Chiral-AGP) or an amylose tris(3,5-dimethylphenylcarbamate) CSP (Chiralpak AD). Of all the approaches, only the direct method using the Chiralpak AD CSP demonstrated separation and enantiomeric resolution of all three analytes within an acceptable run time of 45 minutes. Enantiomeric resolution values of 1.67,3.67 and 3.44 were obtained for flurbiprofen, 4′-hydroxyflurbiprofen and 3′-hydroxy-4′-methoxyflurbiprofen respectively. Semi-preparative isolation of the individual enantiomers of both metabolites, followed by CD analysis, revealed that the elution order on the AD CSP wasR-beforeS-enantiomer for both metabolites and the same as that observed for flurbiprofen. The metabolite elution order was subsequently confirmed on the analysis of urine samples obtained from a healthy volunteer following oral administration of the individual drug enantiomers.

Antimicrobial Activity and Urease Inhibition of Schiff Bases Derived from Isoniazid and Fluorinated Benzaldehydes and of Their Copper(II) Complexes

In order to evaluate the influence of substitution on biological properties of Schiff bases and their metal complexes, a series of differently substituted fluorine-containing Schiff bases starting from the drug isoniazid (isonicotinylhydrazide) were prepared and their structures were established by single-crystal X-ray diffraction. Also, four copper(II) complexes of these Schiff bases were synthesized. The prepared compounds were evaluated for their antimicrobial activity and urease inhibition. Two of the Schiff bases exerted activity against C. albicans. All copper(II) complexes showed excellent inhibitory properties against jack bean urease, considerably better than that of the standard inhibitor acetohydroxamic acid.

DART – LTQ ORBITRAP as an expedient tool for the identification of synthetic cannabinoids

Synthetic cannabinoids as designer drugs constitute a major problem due to their rapid increase in number and the difficulties connected with their identification in complex mixtures. DART (Direct Analysis in Real Time) has emerged as an advantageous tool for the direct and rapid analysis of complex samples by mass spectrometry. Here we report on the identification of six synthetic cannabinoids originating from seized material in various matrices, employing the combination of ambient pressure ion source DART and hybrid ion trap - LTQ ORBITRAP mass spectrometer. This report also describes the sampling techniques for the provided herbal material containing the cannabinoids, either directly as plant parts or as an extract in methanol and their influence on the outcome of the analysis. The high resolution mass spectra supplied by the LTQ ORBITRAP instrument allowed for an unambiguous assignment of target compounds. The utilized instrumental coupling proved to be a convenient way for the identification of synthetic cannabinoids in real-world samples.

Stereospecific analysis of flurbiprofen and its major metabolites in plasma and urine by chiral-phase liquid chromatography

SummaryDirect chiral-phase HPLC methods have been developed for the determination of flurbiprofen and its major metabolites, namely 4′-hydroxyflurbiprofen and 3′-hydroxy-4′-methoxyflurbiprofen, in biological fluids using a derivatized amylose chiral stationary phase (CSP; Chiral-pak AD). Quantification of all three analytes, both free and conjugated, in urine was carried out following liquid-liquid extraction using tandem ultraviolet (UV) and fluorescence detection. Determination of flurbiprofen and the 4′-hydroxy-metabolite in plasma utilized the same CSP but required modification in the mobile phase composition and sole use of fluorescence detection. The urine assay was linear (r>0.998) between 0.05–10 μg mL−1, 0.1–20 μg mL−1 and 0.01–2 μg mL−1 for the enantiomers of flurbiprofen, 4′-hydroxyflurbiprofen and 3′-hydroxy-4′-methoxyflurbiprofen respectively. The plasma assay was linear (r>0.997) between 0.1–6 μg mL−1 and 0.01–0.6 μg mL−1 for the enantiomers of flurbiprofen and 4′-hydroxyflurbiprofen respectively. Both assays, typically yielded within- and between-day imprecision and accuracy values less than 10% for the enantiomers of the different analytes. Initial volunteer studies suggest that the disposition of flurbiprofen displays modest enantioselectivity in humans.

Synthesis and HPLC Enantioseparation of Derivatives of the 3-hydroxyphenylethanone

Abstract Within the framework of the study of the synthesis and high-performance liquid chromatography (HPLC) enantioseparation the series of 9 derivatives of 3-hydroxyphenylethanone was prepared by a well-tried method. The structure of the prepared compounds was confirmed on the basis of interpretation of the IR, UV, 1H NMR and 13C NMR spectra. An enantioseparation of prepared compounds was performed using HPLC on a native teicoplanin (Chirobiotic T) and the amylose tris (3,5-dimethylphenylcarbamate) (Chiralpak AD) chiral stationary phases, which is more suitable for the enantioseparation of all prepared compounds especially with heterocycles in the basic part of a molecule. V ramci študia syntezy a HPLC enantioseparacie bola osvedčenou metodou pripravena seria 9 derivatov 3-hydroxyfenyletanonu aminopropanoloveho typu s rozvetvenymi alkylmi a heterocyklami v bazickej časti molekuly. Štruktura pripravenych zlučenin bola potvrdena interpretaciou IR, UV, 1H NMR a 13C NMR spektier. Enantioseparacia bola uskutočnena HPLC technikou na teikoplaninovej (Chirobiotic T) a na amyloze tris (3,5-dimetylfenylkarbamatovej) (Chiralpak AD) chiralnej stationarnej faze. Porovnanim ziskanych vysledkov sa potvrdilo, že chiralna stationarna faza založena na derivatizovanej amyloze je vhodnejšia na enantioseparačne delenie pripravenych zlučenin, hlavne s heterocyklom v bazickej časti molekuly.

Isomers in the chemistry of iron carbonyls

Abstract The chemistry of iron carbonyls covers wide fields, as shown by a survey covering the crystallographic and structural data of over 560 examples; approximately 10.5% of those examples exist as isomers and are summarized in this paper. Included are distortion (96.7%) and cis-trans (3.3%) isomerism. These are discussed in terms of coordination about iron atom, bond length and interbond angles. Distortion isomers differ only by degree of distortion in Fe-L bond distances and L-Fe-L bond angles, which are the most common. There are iron atoms in the oxidation states, zero, +2 and +3 and cis-trans isomerism (zero only). The iron atoms are two (bent), four (mostly tetrahedral), five (mostly trigonal-bipyramid) and a pseudo-octahedral coordinated with different degree of distortion.

Synthesis, structural characterization and biological activity of novel Knoevenagel condensates on DLD-1 human colon carcinoma

Biologically active Knoevenagel condensates (1-14) of diarylheptanoids: 1,7-bis(3-methoxy-4-hydroxyphenyl)hepta-1,7-diene-3,5-dione and 1,7-bis(3-ethoxy-4-hydroxyphenyl)hepta-1,7-diene-3,5-dione, were synthesized and structurally characterized. Compounds 1-14 exhibited cytotoxicity against colon carcinoma cells, and their antiproliferative effect was associated with a significant decrease of multidrug resistance proteins. One of the underlying mechanisms of these effects is the reduction of intracellular and extracellular SOD enzymes by compounds 1, 12 and 14, which render the tumor cells more vulnerable to oxidative stress.

Synthesis and enantioseparation of derivatives of propranolol

Synthesis and enantioseparation of derivatives of propranolol Propranolol is one of the first prepared and in therapeutic praxis used beta- adrenolytics. In this paper novel derivatives of propranolol with cyclohexylamino and pyrrolidin-1-yl groups in hydrophilic part were prepared. HPLC-enantioseparation propranolol (as reference compound) and of the prepared derivatives has been achieved using a Chiralpak AD CSP based on the amylose tris (3,5-dimethylphenylcarbamate).(R)-enantiomer of the propranolol was prepared by stereoselective synthesis using Jacobsen catalyst. Syntéza a Enantioseparácia Derivátov Propranololu Propranolol je jedným z prvých pripravených a v klinickej praxi používaných beta-adrenolytík. V tejto práci boli pripravené nové deriváty propranololu s cyklohexylamino a pyrolidín-1-ylom v hydrofilnej časti molekuly. HPLC-enantioseparácia propranololu ako štandardu a pripravených deriváTov bola uskutočnená na kolóne CHIRALPAC AD s chirálnou fázou amylóza tris (3,5-dimetylfenylkarbamát). Stereoselektívnou syntézou bol pripravený pomocou Jacobsenovho katalyzátora (R)-enantiomér propranololu.