Basic Compounds (basic + compound)

Distribution by Scientific Domains

Selected Abstracts

Glycogen: A novel branched polysaccharide chiral selector in CE

Jiaquan Chen
Abstract Various chiral selectors have been employed in CE and among them linear polysaccharides exhibited powerful enantioselective properties. Different from linear polysaccharides, the use of branched polysaccharides as chiral selectors in CE has not been reported previously. In this study glycogen belonging to the class of branched polysaccharides was used as a novel chiral selector for the enantiomeric separations for the first time. Since glycogen is electrically neutral, the method is applicable to ionic compounds. Eighteen chiral compounds including 12 basic drugs and six acidic drugs have been tested to demonstrate the potential of this chiral selector. BGE and selector concentrations and buffer pH were systematically optimized in order to obtain successful chiral separations. Among the tested compounds, the enantiomers of ibuprofen, which is an acidic drug, were successfully recognized by 3.0%,w/v glycogen with 90,mM Tris-H3PO4 buffer (pH 7.0). The enantiomers of basic drugs such as citalopram, cetirizine and nefopam were also baseline-resolved with 50,mM Tris-H3PO4 buffer (pH 3.0) containing 3.0% glycogen. Amlodipine belonging to basic compound only gave partial enantioseparation under the above-mentioned condition. [source]

CE coupled to MALDI with novel covalently coated capillaries

Stefan Bachmann
Abstract CE offers the advantage of flexibility and method development options. It excels in the area of separation of ions, chiral, polar and biological compounds (especially proteins and peptides). Masking the active sites on the inner surface of a bare fused silica capillary wall is often necessary for CE separations of basic compounds, proteins and peptides. The use of capillary surface coating is one of the approaches to prevent the adsorption phenomena and improve the repeatability of migration times and peak areas of these analytes. In this study, new capillary coatings consisting of (i) derivatized polystyrene nanoparticles and (ii) derivatized fullerenes were investigated for the analysis of peptides and protein digest by CE. The coated capillaries showed excellent run-to-run and batch-to-batch reproducibility (RSD of migration time ,0.5% for run-to-run and ,9.5% for batch-to-batch experiments). Furthermore, the capillaries offer high stability from pH 2.0 to 10.0. The actual potential of the coated capillaries was tested by combining CE with MALDI-MS for analysing complex samples, such as peptides, whereas the overall performance of the CE-MALDI-MS system was investigated by analysing a five-protein digest mixture. Subsequently, the peak list (peptide mass fingerprint) generated from the mass spectra of each fraction was entered into the Swiss-Prot database in order to search for matching tryptic fragments using the MASCOT software. The sequence coverage of analysed proteins was between 36 and 68%. The established technology benefits from the synergism of high separation efficiency and the structure selective identification via MS. [source]

Analysis of major alkaloids in Rhizoma coptidis by capillary electrophoresis-electrospray-time of flight mass spectrometry with different background electrolytes

Junhui Chen
Abstract CE-based techniques with DAD and detection ESI-TOF-MS have been developed for the analysis of seven protoberberine alkaloids and one aporphinoid alkaloid in Huanglian (Rhizoma coptidis), a well-known traditional Chinese herbal medicine. One aqueous BGE and one nonaqueous BGE were developed for CE-DAD and CE-MS analyses, and the CE-ESI-TOF-MS conditions including nebulizer gas pressure, the sheath-liquid composition, its flow rate, etc. were optimized. Eight main alkaloids in R. coptidis could be separated with baseline resolution by CE-DAD with these two different BGEs, and identified by TOF-MS analysis. Moreover, three major alkaloids (berberine, palmatine, and jatrorrhizine) could be quantified accurately by CE-DAD and CE-MS with the BGE system consisting of 50:50 v/v water and ACN containing 50,mM ammonium acetate at pH,6.8. Both techniques provided similar LODs and could be applied with confidence within similar linear dynamic range. However, reproducibility and speed of analysis were better using CE-DAD. When the CE technique was compared with the RP-HPLC method, the CE-DAD and CE-MS methods provided greater efficiency and faster analysis speed, i.e., achieving baseline resolution for all the eight main basic compounds in less than 14,min. The CE method, as a viable alternative to HPLC, is suitable for use as a routine procedure for the rapid identification and quantification of basic compounds in herbal or natural product applications. [source]

CEC separation of heterocyclic amines using methacrylate monolithic columns

Elena Barceló-Barrachina
Abstract Two methacrylate-based monolithic columns, one with a negatively charged group (sulfonic group) and another with a new monomer N,N -dimethylamino ethyl acrylate (DMAEA), were prepared and tested for the separation of basic compounds by CEC. This new monolithic stationary phase was prepared by the in situ polymerization of DMAEA with butyl methacrylate and ethylene dimethacrylate, using a ternary porogenic solvent consisting of water, 1-propanol and 1,4-butanediol. The performance of this column was evaluated by means of the analysis of a family of heterocyclic amines. Separation conditions such as pH, amount of organic modifier, ionic strength and elution mode (normal or counterdirectional flow) were studied. At the optimal running electrolyte composition, and using the counterdirectional mode, symmetrical electrochromatographic peaks were obtained, with the number of theoretical plates up to 30,000 and a good resolution between closely related peaks. The 2-acrylamido-2-methyl-1-propane-sulfonic acid column was used for CEC-MS, taking advantage of the compatibility of its elution mode (normal flow) with the MS coupling. [source]

Lysosomal sequestration of amine-containing drugs: Analysis and therapeutic implications

Allyn M. Kaufmann
Abstract Amine-containing drugs represent a very important class of therapeutic agents, with the majority of all drugs containing at least one basic nitrogen. For many decades, it has been known that weakly basic compounds can be sequestered into acidic organelles such as lysosomes. Some amines can achieve very high concentrations and induce a dramatic expansion (vacuolization) of the compartment. In the early 70s, Nobel laureate and discoverer of lysosomes, Christian de Duve et al. wrote an elegant commentary describing the theoretical basis for lysosomal sequestration of amines, referring to the process as pH-partitioning and the substrates as lysosomotropics. Recently, a resurgence of interest in the intracellular distribution of drugs has occurred considering its therapeutic importance. Specifically, lysosomal sequestration of amines has received considerable attention for reasons including its involvement in drug resistance, inducement of phospholipidosis, and its influence on whole body distribution/pharmacokinetics. Moreover, the sequestration phenomenon has been recently exploited in the development of a novel drug targeting strategy. This review will focus on these occurrences/developments and conclude with a commentary on the expected impact that knowledge regarding the intracellular distribution of drugs will likely have on future drug development processes. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 729,746, 2007 [source]

Preparation of a stationary phase with s -triazine ring embedded group for reversed phase high-performance LC

Yingyu Li
Abstract This paper describes the synthesis and chromatographic evaluation of a new polar-embedded stationary phase, which utilized 2,4,6-trichloro-1,3,5-triazine as the spacer. The resulting materials were characterized by elemental analysis, IR, and solid-state 13C NMR. Empirical test mixtures were utilized to evaluate the column, and showed that it had good performance for basic compounds and high selectivity for polyaromatic hydrocarbons. Moreover, the novel stationary phase has unique property, especially in the separation of "homologous alkaloids" from natural products. [source]

A simplified protein precipitation/mixed-mode cation-exchange solid-phase extraction, followed by high-speed liquid chromatography/mass spectrometry, for the determination of a basic drug in human plasma

Y.-J. Xue
A simplified protein precipitation/mixed-mode cation-exchange solid-phase extraction (PPT/SPE) procedure has been investigated. A mixture of acetonitrile and methanol along with formic acid was used to precipitate plasma proteins prior to selectively extracting the basic drug. After vortexing and centrifugation, the supernatants were directly loaded onto an unconditioned Oasis® MCX µElution 96-well extraction plate, where the protonated drug was retained on the negatively charged sorbent while interfering neutral lipids, steroids or other endogenous materials were washed away. Normal wash steps were deemed unnecessary and not used before sample elution. The sample extracts were analyzed under both conventional and high-speed liquid chromatography/tandem mass spectrometry (LC/MS/MS) conditions to examine the feasibility of the PPT/SPE procedure for human plasma sample clean-up. For the conventional LC/MS/MS method, chromatographic separation was achieved on a C18, 2.1,×,50,mm column with gradient elution (k,,=,5.5). The mobile phase contained 0.1% formic acid in water and 0.1% formic acid in acetonitrile. For the high-speed LC/MS/MS method, chromatographic separation was achieved on a C18, 2.1,×,10,mm guard column with gradient elution (k,,=,2.2, Rt,=,0.26,min). The mobile phase contained 0.1% formic acid in water and 0.001% trifluoroacetic acid in acetonitrile. Detection for both conventional and high-speed LC/MS/MS methods was by positive ion electrospray tandem mass spectrometry on a ThermoElectron Finnigan TSQ Quantum Ultra, where enhanced resolution (RP 2000; 0.2,amu) was used for high-speed LC/MS/MS. The standard curve, ranging from 0.5 to 100,ng/mL, was fitted to a 1/x weighted quadratic regression model. This combined PPT/SPE procedure effectively eliminated time-consuming sorbent conditioning and wash steps, which are essential for a conventional mixed-mode SPE procedure, but retained the advantages of both PPT (removal of plasma proteins) and mixed-mode SPE (analyte selectivity). The validation results demonstrated that this PPT/SPE procedure was well suited for both conventional and high-speed LC/MS/MS analyses. In comparison with a conventional mixed-mode SPE procedure, the simplified PPT/SPE process provided comparable sample extract purity. This simple sample clean-up procedure can be applied to other basic compounds with minor modifications of PPT solvents. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Comparison between micellar liquid chromatography and capillary zone electrophoresis for the determination of hydrophobic basic drugs in pharmaceutical preparations

S. Torres-Cartas
Abstract The determination of highly hydrophobic basic compounds by means of conventional reversed-phase liquid chromatographic methods has several drawbacks. Owing to the characteristics of micellar liquid chromatography (MLC) and capillary electrophoresis (CE), these techniques could be advantageous alternatives to reversed-phase chromatographic methods for the determination of these kinds of compounds. The objective of this study was to develop and compare MLC and CE methods for the determination of antipsychotic basic drugs (amitryptiline, haloperidol, perphenazine and thioridazine) in pharmaceutical preparations. The chromatographic determination of the analytes was performed on a Kromasil C18 analytical column; the mobile phase was 0.04 m cetyltrimethylammonium bromide (CTAB), at pH 3, containing 5% 1-butanol, at a flow rate of 1 mL/min. The CE separation was performed in a fused-silica capillary with a 50 mm tris-(hydroxymethyl)-aminomethane buffer, pH 7, at an applied voltage of 20 kV, using barbital as internal stardard. The proposed methods are suitable for a reliable quantitation of these compounds in the commercial tablets and drops in terms of accuracy and precision and require a very simple pre-treatment of the samples. By comparing the performance characteristics and experimental details of the MLC and CE methods we conclude that CE seems to be slightly better than MLC in the determination of highly hydrophobic compounds in pharmaceuticals in terms of resolution and economy, taking into account that the limits of detection are not a handicap in pharmaceutical samples. Copyright © 2006 John Wiley & Sons, Ltd. [source]

The effect of stationary phase on lipophilicity determination of , -blockers using reverse-phase chromatographic systems

Tomasz Welerowicz
Abstract Evaluation of lipophilicity parameters for basic compounds using different chromatographic stationary phases is presented. An HPLC method for determination of lipophilic molecule,stationary phase interactions was based on gradient analysis. Differences in correlation between the lipophilicity of compounds and experimental chromatographic results obtained in pseudo-membrane systems showed a strong influence of stationary phase structure and physico-chemical properties. , -Blocker drugs with varying lipophilicity and bio-activity were chosen as test compounds. The stationary phases used for the study were monolithic rod-structure C18 and silica gel octadecyl phase SG-C18 as reference material. The second group was silica gel-based polar-embedded alkylamide and cholesterolic phases. The mobile phase was composed of acetonitrile or methanol with ammonium acetate, and a linear gradient of methanol and acetonitrile in mobile phase was performed. A linear correlation of plots of log kg = f(log P) was observed, especially for polar-embedded phases, and this allowed log PHPLC to be calculated. The behavior of stationary phases in methanol and acetonitrile buffer showed differences between obtained log PHPLC values. Copyright © 2005 John Wiley & Sons, Ltd. [source]