The effect on the stability of the isomers of aminosalicylic acid of formation of their sodium salts has been studied by use
of differential scanning calorimetry and thermogravimetry, coupled with evolved gas analysis by Fourier transform infrared
spectroscopy. X-ray powder diffraction and infrared spectroscopy provided complementary information. The DSC curves for the
sodium salts of all of the isomers showed complex dehydration/decomposition endotherms. From the initial mass losses of the
TG curves, the amounts of water per mole of salt were estimated as 0.5, 2.4 and 1.4 moles for the sodium salts of 3-aminosalicylic
acid, 4-aminosalicylic acid and 5-aminosalicylic acid, respectively. TG-FTIR results for the sodium salt of 3-aminosalicylic
acid showed the evolution of carbon dioxide in three stages: below 150C, between 200 and 300C and continuous formation up
to 500C. This behaviour differs from that of 3-aminosalicylic acid itself, which forms CO2 between 225 and 290C. For the sodium salt of 4-aminosalicylic acid, the formation of carbon dioxide starts from 250C and
is still being formed at about 650C. 4-aminosalicylic acid decarboxylates above 150C. 5-aminosalicylic acid and its sodium
salt showed no evolution of carbon dioxide below 600C.
The thermal behaviour of the aminosalicylic acids is compared with the behaviour of their 1:1 molar ratio physical and kneaded
mixtures with each of three different cyclodextrins (b-, hydroxypropyl-b-, and g-cyclodextrin), using differential scanning
calorimetry and thermogravimetry coupled with evolved gas analysis by Fourier transform infrared spectroscopy. X-ray powder
diffraction and infrared spectroscopy provided complementary information. Comparison of the effects of the different cyclodextrins
on the behaviour of the individual aminosalicylic acid isomers shows that hydroxypropyl-b-cyclodextrin has the greatest interaction
with 3-aminosalicylic acid and 5-aminosalicylic acid, followed by g-cyclodextrin, while b-cyclodextrin generally shows the
least interaction. For 4-aminosalicylic acid, the effect of g-cyclodextrin seems to be more marked than for 3-aminosalicylic
acid and 5-aminosalicylic acid.
ligands complexes of metal(II) containing nitrogen donor ligands [ 1 ].
The salicylic acid derivatives are widely used for treatment of various diseases [ 2 ]. 4-aminosalicylicacid (4-amino-2-hydroxybenzoic acid or p -aminosalicylicacid) which
Authors:S. Agotonovic-Kustrin, B. Glass, M. Brown, and M. Rotich
The application of classical QSAR and molecular modelling to the inclusion complexation of natural and modified cyclodextrins
(CDs) with carboxylic acid derivatives as guest molecules was examined. Information was available on the thermal behaviour,
in the solid-state of benzoic acid (BA), salicylic acid (SA), and various substituted aminosalicylic acids (3-aminosalicylic
acid, 3-ASA, 4-aminosalicylic acid, 4-ASA and 5-aminosalicylic acid, 5-ASA), as well as on the thermal behaviour of 1:1 molar
ratio physical and kneaded mixtures of these acids with each of three different cyclodextrins, β-, (BCD) 2-hydroxypropyl-β-,
(HPBCD) and γ-cyclodextrin (GCD). The thermal behaviour of the binary (1:1 stoichiometry) mixtures was modelled using stepwise
multiple regression (SMR). Two models for the prediction of the percentage mass loss and enthalpy of dehydration of the physical
mixtures were established with correlation coefficients (r) of 0.79 and 0.92, respectively. Decreased correlation in the thermal behaviour of kneaded mixtures indicated significant
interaction and possible formation of inclusion complexes.
Authors:Alina Pyka-Pająk, Małgorzata Dołowy, and Katarzyna Bober
The aim of the work was the chromatographic separation of salicylic acid and their derivatives, i.e., acetylsalicylic acid, salicylanilide, salicylaldehyde, salicylamide, methyl salicylate, phenyl salicylate, 2,5-dihydroxybenzoic acid, salicylhydroxamic acid, 3,5-dinitrosalicylic acid, 3-aminosalicylic acid, 4-aminosalicylic acid, and 5-aminosalicylic acid by use of adsorption thin-layer chromatography (normal-phase thin-layer chromatography [NPTLC]) and partition thin-layer chromatography (reversed-phase thin-layer chromatography/high-performance thin-layer chromatography [RP-TLC/HPTLC]). Three qualitatively and quantitatively different mobile phases were used for the separation of salicylic acid and its derivatives. Cluster analysis (single linkage method, Euclidean distance) allowed the evaluation of the suitability of the chromatographic conditions used to separate the pairs of tested compounds. The cluster analysis data indicate that the composition of the mobile phase is fundamental in the process of separation of the analyzed compounds by use of NP-TLC. The best separation of the studied substances was observed in the case of mobile phase n-hexane—diethyl ether—acetic acid (80%) in different volume ratios. The similarity analysis of the results obtained by use of RP-TLC/HPTLC revealed that the type of chromatographic plates influences significantly the quality of separation of the tested compounds. The best conditions for the separation by RP-TLC were obtained on silica gel RP-18 F254 plates. The present study indicates that the cluster analysis represents a simple-to-use and powerful chemometric tool in the prediction of TLC separation of medically important salicylic acid derivatives under various chromatographic conditions. It can be helpful in the quality control of multicomponent synthetic preparations containing these compounds or in the chemical standardization of plant products consisting of salicylic acid and related compounds.
Authors:Jolanta Flieger, Piotr Paneth, Krystyna Giełzak-Koćwin, and Małgorzata Tatarczak
We report the chromatographic behavior of the antitubercular drugs isoniazid (INH), pyrazinamide (PYR), ethambutol (ETB), and
-aminosalicylic acid (PAS) in reversed-phase TLC with organic aqueous mobile phases modified with Cu(II) chloride. The spectra of the free ligands and complexes formed during chromatography were measured densitometrically by use of a scanner equipped with a diode-array detector and compared in the range 200–700 nm. The complexes of Cu(II) with isoniazid and ethambutol were isolated on a micropreparative scale. The structures of the INH-Cu and EMB-Cu complexes were analyzed by electron paramagnetic resonance (EPR) spectroscopy and illustrated graphically by molecular modeling using GaussView software.
The chromatographic behavior of the phenolic drugs niclosamide, hexachlorophene, ibuprofen, pentazocine, ethamivan, bithionol, salicylanilide, caffeic acid,
-coumaric acid, 4-aminosalicylic acid, ferulic acid, and methyldopa has been investigated on RP8F
TLC plates with methanol-water mixtures in different volume proportions as mobile phases. Linear relationships were obtained between the
values of the drugs and the volume fraction of methanol in the mobile phase. Retention values,
, were extrapolated to zero methanol content and the lipophilicity values
obtained were compared both with measured partition coefficients (log
) and with partition coefficients (AlogPs, IAlogP, AB/logP, COSMOFFrag, miLogP, KOWWIN, and xlogP) calculated using seven different software products. Comparison of the calculated partition coefficients revealed IAlogP, KOWWIN, miLogP, and
(where is the average of all the theoretical partition coefficients) usually correlate best with chromatographic lipophilicity
. The results indicate that chromatographic lipophilicity
can be used as a measure of the lipophilicity of the phenolic drugs investigated.