Microscopic Protonation Deprotonation Equilibria of the Antiinflammatory Agent Piroxicam

The microscopic ionization behavior of piroxicam was investigated using two different approaches, i.e., direct UV spectroscopy and an indirect analogue approach (deductive method). The best microscopic pK(a) values (PKa12 = 4.60, pK(a21) = 5.40, pK(a22) = 2.72, and pK(a11) = 1.92) were obtained by the deductive method using as pK(a22) the pK(a) of the enolic O-methylated piroxicam 2. The results show remarkable electrostatic effects in the protonation/deprotonation equilibria, a marked increase in the acidity of the enolic function (2.68 pK(a) units) being caused by the pyridinium group. The electronic structure of piroxicam was studied based on H-1-NMR chemical shifts at various ionization states, indicating an extended electron conjugation through the molecule. The partition measurements in octan-1-ol/H2O of zwitterionic compound 3 (the pyridyl N-methyl derivative of piroxicam (1)) suggest that the two opposite charges in zwitterionic piroxicam are indeed in a close intramolecular proximit

Characterisation of reversed-phase liquid chromatographic columns by chromatographic tests. Rational column classification by a minimal number of column test parameters

The European Pharmacopoeia (Ph. Eur.) and other official compendia give only a general description of the stationary phase in the description of a liquid chromatographic method. Therefore the selection of a column giving suitable selectivity presents difficulties. Earlier, a test procedure was proposed that allows to measure 36 chromatographic parameters which have been described for characterising stationary phases. This procedure was carried out on 69 reversed-phase liquid chromatography (RP-LC) columns. This paper focuses on the classification of RP-LC stationary phases based on chromatographic parameters. A chemometric study was conducted using 24 parameters that could be measured in a repeatable and reproducible way. Principal component analysis was used to classify the columns and to estimate the minimal number of parameters necessary for a rational classification. It is shown that after reducing the number of parameters from 24 to four or three, similar classifications were obtained. The column classifications were compared to the European Pharmacopoeia stationary phase description and to the column properties obtained from the manufacturers</p

Characterisation of reversed-phase liquid chromatographic columns by chromatographic tests. Evaluation of 36 test parameters: repeatability, reproducibility and correlation

The European Pharmacopoeia (Ph. Eur.) or other official compendia give only a general description of the stationary phase in the description of a liquid chromatographic method. Therefore the selection of a column giving suitable selectivity presents difficulties. Earlier, a test procedure was proposed that allows measurement of a number of parameters which are reported to be representative for stationary phase characteristics. This paper describes how the test procedure was applied on 69 RP-LC C18 columns. Chromatographic parameters obtained as test results were evaluated, and their repeatability, reproducibility and correlation were examined</p