ABSTRACT
The synthesis, stereostructure, and enantiomeric separation by chromatography of a new, chiral anxiolytic agent, deramciclane fumarate (2, (-)-[1R,2S,4R]-2-(2-dimethylaminoethoxy)-2-phenyl-1,7, 7-trimethylbicyclo[2.2.1]heptane fumarate, EGIS-3886), is described. The optical antipode and the racemate of compound 2 were also prepared. The structure was determined by single crystal X-ray diffraction analysis. The enantiomeric separation was accomplished by HPLC on Chiralcel OD (250 x 4.6 mm; 10 microm) and hexane-ethanol (99.5:0.5) as mobile phase at room temperature. The enantiomeric purity of the synthesized drug substance proved to be very high (>99. 9%). Some statements published earlier on the stereostructure of deramciclane fumarate are critically discussed.
Subject(s)
Anti-Anxiety Agents/chemistry , Camphanes/chemistry , Anti-Anxiety Agents/isolation & purification , Camphanes/isolation & purification , Chromatography, High Pressure Liquid , Stereoisomerism , X-Ray DiffractionABSTRACT
The manufacture-characteristic impurity profile of nifedipine drug substance was studied by HPLC and on-line LC/MS coupling. Using a new gradient HPLC procedure and MS detection, spectroscopic evidences for the chemical structure of some previously unknown minor impurities (all under 0.1%) were obtained.
Subject(s)
Nifedipine/standards , Chromatography, High Pressure Liquid/methods , Mass Spectrometry/methods , Molecular Structure , Nifedipine/chemistry , Nifedipine/isolation & purificationABSTRACT
The identification and quantification of potential impurities of Tofisopam have been studied by high performance liquid chromatography. The best separation was obtained in a reversed phase system using a C18 stationary phase and 46:31:23 mixture of 0.01 M aqueous 1-hepatanesulphonic acid-sodium-acetonitrile-methanol as the mobile phase. System suitability parameters and method validation are also presented and discussed. The elaborated method was suitable for the determination of the conformational isomer ratio of Tofisopam in various solvents and for the evaluation of Challenge Test.
Subject(s)
Anti-Anxiety Agents , Benzodiazepines/chemistry , Chromatography, High Pressure Liquid , Drug ContaminationABSTRACT
The thermal behaviour of Selegiline (a chiral, non racemic pharmaceutical used in the therapy of Parkinson disease) was studied by differential scanning calorimetry (DSC) for determining the enantiomeric purity (e.p.) of the bulk substance. It has been found, that (i) the binary phase diagram (melting point phase diagram) of the R/S enantiomer mixtures is characteristic to that of the true racemic compounds; (ii) the melting behaviour of the R/S binary mixtures follows the thermodynamic laws (i.e. the Schröder-Van Laar and the Prigogine-Defay equations); (iii) the e.p. of the highly purified bulk substance can be expressed as "DSC purity" (this latter is obtained from the Van't Hoff equation) and the microcalorimetric method as above gives good reproducibility; (iv) due to the minor impurities (other than the S(-) enantiomer) the obtained e.p. (expressed as DSC purity) can be higher but not lower than the actual e.p. of the investigated substance.
Subject(s)
Selegiline/chemistry , Calorimetry, Differential Scanning , StereoisomerismABSTRACT
A thin-layer chromatographic (TLC) method is described for the enantiomeric separation of chiral carboxylic acids using chiral derivatization and non-chiral TLC conditions (ordinary plates and mobile phases) to separate the diastereomeric carboxamides obtained. New chiral derivatizing agents, "levobase" (1R, 2R)-(-)-1-(4-nitrophenyl)-2-amino- 1,3-propanediol, and "dextrobase" (the enantiomer of levobase) are used for carboxamide formation in the presence of dicyclohexylcabodiimide as coupling agent. The procedure is very simple and convenient to carry out. Good resolution is obtained for a wide range of carboxylic acid enantiomeric pairs containing one to two chiral centres.
ABSTRACT
PIP: There is a need for improved contraception standards for premenopausal women. Special precautions should be taken for this group. In order to study the special contraceptive needs of the premenopausal women, the fertility trends in the 35-50 year age group were investigated. Pregnancy rates showed a gradual decline with an increase after age 44, the incidence of anovulatory cycles increased markedly after age 40, and concomitantly, the coital frequency steadily decreased. On the basis of propsective studies, it was possible to construct an Age Specific Fertility Score which proved to be a valuable tool in selecting the most suitable, low-risk contraceptive method. It was also possible to construct the Age Specific Fertility Index.^ieng
