HPLC Method for Chiral Separation and Quantification of Antidepressant Citalopram and Its Precursor Citadiol

HPLC method enabling chiral separation and determination of citalopram (CIT), a widely used antidepressant, and its synthetic precursor citadiol in one analysis was developed and validated. Moreover, supercritical fluid chromatography was also tested and was proved to be less effective for this separation purpose. The optimized HPLC system was composed of Chiralcel OD-H column and n-hexane/propane-2-ol/triethylamine 96/4/0.1 (v/v/v) as mobile phase, column temperature 25 °C, flow rate 1.0 mL min^?1, UV detection at 250 nm. The effects of amount of propane-2-ol, triethylamine addition, and temperature on enantioselectivity and resolution of the enantiomers were evaluated. The method was found to be suitable for determination of the enantiomeric purity of CIT in bulk drugs. Enantiomers of CIT were determined in two commercially available pharmaceuticals.     

Analysis of trace degradation products (decarboxylated diastereoisomers) of S-adenosylmethionine by electrophoresis in capillaries with cationic coatings (N-methylpolyvinylpyridinium or divalent barium)

Commercial preparations of S‐adenosylmethionine (SAM) when analyzed in uncoated capillaries show a minute impurity believed to be decarboxylated (dc) SAM. By using two types of cationic coatings, thus reducing the electro‐endo‐osmotic flow (EOF), it was possible to separate this impurity into two diastereoisomers of dcSAM. The coatings evaluated for this purpose were: (i) N‐methylpolyvinylpyridinium, used under reversed EOF at acidic conditions (pH 4.0) and (ii) deposition of divalent barium at alkaline pH values (pH 9.4), providing reduced EOF. Under these conditions, it was possible to separate this impurity into two diastereoisomers, which by chemical synthesis were indeed proven to be dcSAM. It was further demonstrated that, in the alkylation of 5′‐methylthioadenosine by 3‐bromopropylamine in bromidric acid to dcSAM, another minute impurity was present, proven, via mass spectrometry, to consist of S‐(5′‐adenosyl)‐3‐thiopropylamine (decarboxylated and demethylated (dc‐SAH)). The LOD for the two dcSAM diastereoisomers was assessed as 17.5 μg/mL and their LOQ as 25.5 μg/mL. By the barium‐based protocol it was possible to quantify the dcSAM, present in a commercial sample of SAM, as a 0.1% impurity.     

Utilization of zirconia stationary phase as a tool in drug control

Zirconia-based stationary phases represent an interesting alternative to silica-based materials. Two zirconia-based stationary phases were studied as an option for use in drug analysis. The different properties of zirconia material, distinct from RP silica-columns, were employed for the development of a novel and rapid stability monitoring HPLC method. This method enables simultaneous control of possible degradation processes of active substance (ibuprofen) as well as antimicrobial excipients (methyl-and propylparaben). The separation of ibuprofen, its two main degradation products 2-(4-isobutyrylphenyl)propionic acid and 4-isobutylacetophenone, parabens, and 4-hydroxybenzoic acid as their degradation product was successfully accomplished on a Zr-CarbonC18 column using a mobile phase consisting of acetonitrile-phosphate buffer (pH 4.8)-propan-2-ol (27:56:17, v/v/v). Detection was performed at 258 nm and the analysis was completed within 17 minutes.     

X-ray fluorescence determination of total sulfur in fly ash

Standard addition, double dilution and standard calibration were used for x-ray fluorescence (XRF) determinations of sulfur in fly ashes. Samples were analysed as pellets prepared by mixing with acrylate copolymer or with microcrystalline cellulose (in the case of the double dilution method). Lithium sulfate was used for the standard addition method and also as standard with known sulfur content for the double dilution method. Fly ashes analysed by optical emission spectrometry with an inductively coupled plasma (ICP-OES) were used as standards for the standard calibration XRF method. Sulfur was determined in the range of ca. 10^–1–10⁰ % S. For the fly ashes from the North-Bohemian brown coals, the differences between the XRF determinations and the ICP-OES determinations ranged from ca. 1.4 to 10% rel. and precision (repeatability) was better than 10% (RSD). The standard calibration method is suitable for routine analyses of real samples of similar nature. The methods of standard addition and double dilution are rather laborious in sample preparation compared with the standard calibration. Received: 27 October 1998 / Revised: 5 March 1999 / Accepted: 11 March 1999     

Fast electrophoretic separation of sulfur- and selenium-containig amino acid enantiomers with vancomycin as a chiral selector in coated capillaries

Baseline separation of the enantiomers of the negatively charged 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatives of cystine, methionine, ethionine, and their seleno analogs can be achieved in 3–5 min with capillary electrophoresis in polyacrylamide coated capillaries and submillimolar concentrations of vancomycin as the chiral selector. In addition to the vancomycin concentration, the separation is affected by the type, concentration and pH of the buffer. Good buffers are more suitable than phosphate buffer. At pH values above the isoelectric point of vancomycin the mobility difference between the enantiomers becomes smaller. This effect is larger than would be expected from the reversal of the vancomycin migration alone.     

Strongly regular family of boundary-fitted tetrahedral meshes of bounded C2 domains

We give a constructive proof that for any bounded domain of the class C² there exists a strongly regular family of boundary-fitted tetrahedral meshes. We adopt a refinement technique introduced by K?í?ek and modify it so that a refined mesh is again boundary-fitted. An alternative regularity criterion based on similarity with the Sommerville tetrahedron is used and shown to be equivalent to other standard criteria. The sequence of regularities during the refinement process is estimated from below and shown to converge to a positive number by virtue of the convergence of q-Pochhammer symbol. The final result takes the form of an implication with an assumption that can be obviously fulfilled for any bounded C² domain.     

Synthesis of novel azanorbornylpurine derivatives

Azanorbornylpurine derivatives were prepared by Mitsunobu reaction of appropriate hydroxyazanorbornane derivative with 6-chloropurine or construction of purine base at azanorbornylamines. The prepared target compounds were evaluated for antiviral activity and effect on neuronal and muscle nicotinic acetylcholine receptors.