Petr Kastner

Study of the lipophilicity of potential antituberculotic compounds by reversed-phase thin-layer chromatography

Reversed-phase (RP) TLC retention behavior has been examined for two series of potential antituberculotic drugs. Effects of the type and proportion of the organic component of the mobile phase were tested, because these can affect retention. Experimentally measured lipophilicity values and values calculated by means of a computational method were compared to determine the extent of any correlation. It was found that substitution of the aromatic ring, in particular with chlorofluoro or more complicated substituents, negatively affected the correlation between measured and calculated values.

Relationship between structure and reversed-phase thin-layer chromatographic lipophilicity parameters in a group of piperazine derivatives

Abstract The RM values of substituted piperazine derivatives, I, have been determined on silanized silica gel plates with buffered aqueous acetone with or without n-octylamine as the mobile phase. Chromatographically determined lipophilicity of substances containing aromatic nuclei that are separated by a sufficiently flexible chain, presented a decrease in comparison with the lipophilicity calculated on the basis of tabulated fragmental constants. The intramolecular hydrophobic interaction of aromatic nuclei resulting from their stacking conformation could be a probable explanation for this phenomenon.

Reversed-phase thin-layer chromatographic determination of the lipophilicity of potential antituberculotic compounds

RPTLC retention characteristics have been examined for two series of potential antituberculotic drugs. Various effects were tested which can be manifested in the values of properties measured — i.e. the effect of the type and proportion of the organic component of the mobile phase, and the effect of the pH of the aqueous component of the mobile phase. Experimentally obtained measures of lipophilicity were correlated with each other and with values calculated by a computational method. In this study some substituents, in particular nitro groups or more complicated substitution of the aromatic ring, negatively affected the correlation of the measured values with those calculated.

LIPOPHILICITY CHARACTERIZATION BY REVERSED-PHASE HPLC OF POTENTIAL ANTITUBERCULOTICS

ABSTRACT Lipophilicity is one of the properties which influence the partition of a substance in biological media. The reversed-phase high-performance liquid chromatographic (RP-HPLC) capacity factors k of two series of 2-benzylthioderivatives, newly synthesized as potential antituberculous drugs, were determined on a C-18 stationary phase with methanol–water as the mobile phase, using UV detection. The measured log k values were compared with the log P values obtained by means of a mathematical method. High correlation was found between log P and log k values.

Reversed‐Phase High Performance Liquid Chromatographic Determination of Lipophilicity of Potential Antituberculosis Compounds

Abstract Lipophilicity is one of the properties, which influences the partition of a substance in biological media. The reversed‐phase high performance liquid chromatography (RP‐HPLC) capacity factors k of 27 2‐benzylsulfanyl derivatives of benzothiazole, newly synthesized as potential antituberculous drugs, were determined on a C18 stationary phase with methanol–water as the mobile phase, using UV detection. The measured log k values were compared with the log P values obtained by means of mathematical methods. High correlation was found between log P and log k values.

Mucoadhesive plasticized system of branched poly(lactic-co-glycolic acid) with aciclovir

Abstract Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug–polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00 s−1 at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at Tg depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters.

Determination of lipophilicity of potential antituberculous drugs by reversed-phase high performance liquid chromatography

The RP-HPLC capacity factors k of two series of 4-benzylthio-derivatives, newly synthetised as potential antituberculous drugs, were determined on two types of C18 columns with methanol–water as the mobile phase, using UV detection. The measured log k values were compared with the log P values obtained by means of mathematical programmes and methods. High correlation was found between log P and log k values.

Study of hydrophobic properties of biologically active open analogues of flavonoids.

Hydrophobicity can either be determined experimentally or predicted by means of commercially available programs. In the studies concerning biological activities of pyrazine analogues of chalcones, 3-(2-hydroxyphenyl)-1-(pyrazin-2-yl)prop-2-en-1-ones were more potent than the corresponding 3-(4-hydroxyphenyl)-1-(pyrazin-2-yl)prop-2-en-1-ones. As the difference in lipophilicity may be a factor responsible for the difference in the potency, R(M) values of the compounds were determined by RP-TLC and compared with logP values calculated by various commercially available programs. Important discrepancies were found between experimental and computational lipophilicity data. Therefore, we have tried to find a reliable method for calculating R(M) values from in silico derived molecular parameters. The R(M) values obtained with the chromatographic system consisting of Silufol UV 254 plates impregnated with silicon oil as the stationary phase and acetone-citrate buffer (pH=3) 50:50 (v/v) as the mobile phase correlated well with van der Waals volumes (V(W)) and hydration energies [Formula: see text] derived of molecular models calculated on RHF/AM1 level.

Isolation and identification of amphetamines in urine by thin-layer chromatography

Amphetamine derivatives are psychostimulating drugs. They are characterized by their strong central stimulating, anorectic, and peripheral sympathomimetic effect. They are used in the therapy of narcolepsy; amphetamine derivatives are relatively successful and, because administration is for a short time only, the effects of intolerance do not appear, in contrast with their use in the treatment of anorexia. Amphetamine derivatives incite a state of increased wakefulness, avert sleep, and accelerate psychomotor activity; the brain is able to capture and process a greater number of stimuli. This effect is, however, achieved at the cost of the quality of brain function. Alerting amines are abused for their euphoric effects by addicts. Amphetamine (AP) is a typical representative of the psychostimulants. It is well adsorbed from the gastrointestinal tract and easily penetrates the blood–brain barrier. The biological half-life is 12–34 h, depending on the pH of urine. Many individuals orally abuse amphetamine for abolition of fatigue, enhancement of wakefulness, and mood elevation. It appears in urine 20 min after administration and chronic consumers can have urine levels in the range