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A micellar liquid chromatographic method was developed for the green enantioseparation of racemic amino alcohols using an aqueous solution of the mixed surfactants as an alternative for organic solvents. In this study, the derivatives of the amino alcohols were synthesized using highly reactive chiral esters of (S)-levofloxacin (Lfx) under microwave conditions, and an aqueous solution of the surfactants (Brij-35 and SDS) was used for the enantioseparation of the synthesized diastereomeric derivatives (DDs) of amino alcohols using reversed-phase HPLC. The activated ester of Lfx was synthesized by reacting with N-hydroxybenzotriazole and characterized using UV, IR, 1 H NMR, high-resolution mass spectrometry, and elemental analysis. The DDs of racemic amino alcohols were separated on a C 18 column using micellar LC. Chromatographic conditions were optimized by varying the concentration of the surfactants in aqueous solution and by varying the concentration and pH of the buffer. The green assessment score was calculated for the developed method (score: 82, an excellent green method). In addition, the density functional theory calculations were performed to develop the lowest energy-optimized structures of DDs. The method was validated according to the International Conference of Harmonization guidelines, and the retention factor (k), selectivity factor (α), resolution factor (R S ), limit of detection (0.198 ng mL -1 or 0.291 pM mL -1 ), and limit of quantification (0.594 ng mL -1 or 0.873 pM mL -1 ) were calculated., (© 2020 John Wiley & Sons, Ltd.)

Objectives: To screening of bacteria with cyclic amino alcohol deamination activity for enantioselective synthesis of chiral cyclic β-amino alcohols., Results: A new strain named Arthrobacter sp. TYUT010-15 with the (R)-selective deamination activity of cyclic β-amino alcohol has been isolated from nature via a high throughput solid-phase screening method. The reaction conditions of TYUT010-15 were optimized. Using the resting cell of TYUT010-15 as the catalyst, kinetic resolution of trans-2-aminocyclopentanol, trans-2-aminocyclohexanol and cis-1-amino-2-indanol was carried out to afford (1S, 2S)-trans-2-aminocyclopentanol, (1S, 2S)-trans-2-aminocyclohexanol and (1R, 2S)-cis-1-amino-2-indanol in > 99% ee and 49.6-50% conversion. Four aromatic β-amino alcohols and two amines were also resolved, (S)-β-amino alcohols and (R)-amines were obtained in > 99% ee. Preparation experiment was conducted with 200 mM (23.2 g L -1 ) racemic trans-2-aminocyclohexanol, yielding the desired (1S, 2S)-trans-2-aminocyclohexanol in 40% isolated yield, > 99% ee and 5.8 g L -1 d -1 space time yields., Conclusions: This study provides a high throughput solid-phase method for screening of bacteria with cyclic amino alcohol deamination activity and a first example for practical preparation of chiral cyclic β-amino alcohol by Arthrobacter sp. TYUT010-15.

A novel multifunctional aminophenylboronic acid connected to a diphenylketone gives both circular dichroism and fluorescence signals by in situ generation of a BODIPY-like chromophore in the presence of aminoalcohols. DFT calculations were used to understand the role of each functional group in the mechanism. This new sensor can distinguish different aminoalcohols and quantitatively indicate the concentration of the substrate, allowing for the convenient determination of the ee of racemic mixtures with a single probe.

Enantioseparation of limonene-based bicyclic 1,3-aminoalcohols and 1,3,5- and 1,3,6-aminodiols was performed by normal-phase high-performance liquid chromatographic and supercritical fluid chromatographic (SFC) methods on polysaccharide-based chiral stationary phases. The effects of the composition of the mobile phase, the column temperature and the structures of the analytes and chiral selectors on retention and selectivity were investigated by normal-phase LC and SFC technique. Thermodynamic parameters derived from selectivity-temperature-dependence studies were found to be dependent on the chromatographic method applied, the nature of the chiral selector and the structural details of the analytes. Enantiorecognition in most cases was enthalpically driven but an unusual temperature behavior was also observed: decreased retention times were accompanied by improved separation factors with increasing temperature, i.e. some entropically driven separations were also observed. The elution sequence was determined in all cases. The separation of the stereoisomers was optimized in both chromatographic modalities., (© 2019 John Wiley & Sons, Ltd.)

(R)-3-amino-1-butanol is a key intermediate of Dolutegravir for the treatment of HIV/AIDS and its green and efficient biosynthesis has attracted a great deal of attention. Transaminases are currently used as promising biocatalyst for the synthesis of chiral amines. However, many transaminases have (S)-specificity and (R)-selective transaminases were less exploited and studied, making the production of (R)-amines remain challenging. In this study, a novel transaminase from Actinobacteria sp. (As-TA) was obtained and applied for the biosynthesis of (R)-3-amino-1-butanol by transferring the amino group from isopropylamine to 4-hydroxy-2-butanone. After optimization of the reaction condition and using a substrate fed-batch strategy, the conversion of 100, 200, 300, 400 and 500 mM 4-hydroxy-2-butanone reached 100%, 94.9%, 86.1%, 76.1% and 70.9%, respectively. (R)-3-amino-1-butanol with a maximum yield of 29.6 g/L and 99.9% e.e. value was obtained. This was the first time demonstrating the successful biosynthesis of (R)-3-amino-1-butanol with transaminase as biocatalyst and the obtained As-TA enriched the enzyme pool of transaminase with (R)-specificity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chiral β-amino alcohols are very important chiral building block for preparing bioactive compounds for use in pharmaceutical and fine chemical industries. Synthesis of chiral β-amino alcohols by transaminase is big challenging due to the strict substrate specificities and very low activity of the enzyme. In this work, a (R)-selective ω-transaminase (MVTA) from Mycobacterium vanbaalenii was employed as a biocatalyst for the first time for the synthesis of chiral β-amino alcohol via kinetic resolution and asymmetric reductive amination. The enzyme was purified and characterized. Kinetic resolution of a set of racemic β-amino alcohols including two cyclic β-amino alcohols by MVTA was demonstrated, affording (R)-β-amino alcohols, (1S, 2S)-trans-2-aminocyclopentanol and (1R, 2S)-cis-1-amino-2-indanols in >99% ee and 50-62% conversion. Asymmetric reductive amination of three α-hydroxy ketones (10-300 mM) by MVTA was conducted, (S)-β-amino alcohols were obtained with >99% ee and 80-99% conversion. Preparation experiment for the reductive amination of 200 mM 2-hydroxyacetophenone by the resting cells of recombinant E. coli (MVTA) was proceeded smoothly and product (S)-2-amino-2-phenylethanol was obtained with 71% isolated yield, >99% ee and 68.6 g/L/d volumetric productivity. The current research proved that the MVTA is a robust enzyme for the preparation of chiral β-amino alcohol with high volumetric productivity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To investigate the efficiency of a new cascade biocatalysis system for the conversion of R, S-β-amino alcohols to enantiopure vicinal diol and β-amino alcohol., Results: An efficient cascade biocatalysis was achieved by combination of a transaminase, a carbonyl reductase and a cofactor regeneration system. An ee value of > 99% for 2-amino-2-phenylethanol and 1-phenyl-1, 2-ethanediol were simultaneously obtained with 50% conversion from R, S-2-amino-2-phenylethanol. The generality of the cascade biocatalysis was further demonstrated with the whole-cell approaches to convert 10-60 mM R, S-β-amino alcohol to (R)- and (S)-diol and (R)- and (S)-β-amino alcohol in 90-99% ee with 50-52% conversion. Preparative biotransformation was demonstrated at a 50 ml scale with mixed recombinant cells to give both (R)- and (S)-2-amino-2-phenylethanol and (R)- and (S)-1-phenyl-1, 2-ethanediol in > 99% ee and 40-42% isolated yield from racemic 2-amino-2-phenylethanol., Conclusions: This cascade biocatalysis system provides a new practical method for the simultaneous synthesis of optically pure vicinal diol and an β-amino alcohol.

A new enantioselective potentiometric sensor containing R-type chiral porous organic cage CC9 as the chiral selector was designed for the assay of 2-aminobutanol. Optimized membrane electrodes displayed a linear dynamic range from 10 -3  ~ 10 -1  mol·L -1 with a detection limit of 2.5 × 10 -4  mol·L -1 and a Nernstian response of 27 ± 0.5mV·decade -1 toward S-2-aminobutanol within the pH range 7.0-10.0. The potentiometric enantioselectivity coefficient ( logKS,RPot) of this sensor was -1.333, indicating that the porous organic cage-based electrode exhibited good discrimination toward S-2-aminobutanol over R-2-aminobutanol., (© 2017 Wiley Periodicals, Inc.)

Efficient syntheses of chiral fragments derived from chiral amino alcohols are described. Several unique scaffolds were readily accessed in 1-5 synthetic steps leading to 45 chiral fragments, including oxazolidinones, morpholinones, lactams, and sultams. These fragments have molecular weights ranging from 100 to 255 Da and are soluble in water (0.085 to >15 mM).

Rationale: Aminoalcohol-diterpenoid alkaloids were found to be a group of cardioactive substances in the lateral roots of Aconitum carmichaeli Debx. Studies on the fragmentation behaviors and features of these alkaloids in mass spectrometry would be important for their structural identification and in vivo metabolic research, which has not received much attention thus far., Methods: In this study, the fragmentation behaviors of 14 aminoalcohol-diterpenoid alkaloids were investigated by utilizing high-resolution time-of-flight tandem mass spectrometry. By analysis of the obtained MS(2) data, we summarized the fragmentation features of the corresponding alkaloids under different collision energy., Results: The dissociation of functional groups from the skeleton was observed as the main fragmentation way in electrospray ionization (ESI) mode. The order of fragmentation sites was C1/C3 > C16 > C15 > C6 > N, with loss of one or more CH3OH, H2O, C2H4 (substituent on N atom) or CO (at C15 ) groups., Conclusions: The first systematic investigations on the fragmentation of aminoalcohol-diterpenoid alkaloids are described in this paper, setting the stage for an in-depth identification and study of the corresponding components in complex systems., (Copyright © 2015 John Wiley & Sons, Ltd.)

Present study aimed at graphene surface modification to achieve selective analyte binding in dispersive solid phase extraction. Magnetic graphene - polystyrene sulfonic acid (MG-PSS) cation exchange nano-composite was prepared by non-covalent wrapping method. Composite was characterized by FT-IR and zeta potential. Material exhibited good dispersion in water and high exchange capacity of 1.97±0.16mMg(-1). Prepared nano-sorbent was then exploited for the cation exchange extraction and gas chromatography mass spectrometric analysis of Chemical Weapons Convention relevant aminoalcohols and ethanolamines from aqueous samples. Extraction parameters such as sorbent amount, extraction time, desorption conditions and sample pH were optimized and effect of common matrix interferences such as polyethylene glycol and metal salts was also studied. Three milligram of sorbent per mL of sample with 20min of extraction time at room temperature afforded 70-81% recoveries of the selected analytes spiked at concentration level of 1μgmL(-1). Method showed good linearity in the studied range with r(2)≥0.993. The limits of detection and limits of quantification ranged from 23 to 54ngmL(-1) and 72 to 147ngmL(-1), respectively. The relative standard deviation for intra- and inter-day precision ranged from 4.6 to 10.2% and 7.4 to 14.8% respectively. Applicability of the method to different environmental samples as well as the proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons (OPCW) was also ascertained., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A 1,1'-bi-2-naphthol (BINOL)-based chiral aldehyde in combination with Zn(II) shows a highly enantioselective fluorescent response toward functional chiral amines at λ>500 nm. However, the combination of salicylaldehyde and Zn(II) gives the same fluorescent enhancement for both enantiomers of a functional chiral amine at λ=447 nm. By using the fluorescent responses of the combination of the BINOL-based chiral aldehyde, salicylaldehyde and Zn(II) at the two emission wavelengths, both the concentration and enantiomeric composition of functional chiral amines such as amino alcohols, diamines, and amino acids can be simultaneously determined by a single fluorescent measurement. This work provides a simple and convenient method for chiral assay., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of whole-body imaging at single-cell resolution enables system-level approaches to studying cellular circuits in organisms. Previous clearing methods focused on homogenizing mismatched refractive indices of individual tissues, enabling reductions in opacity but falling short of achieving transparency. Here, we show that an aminoalcohol decolorizes blood by efficiently eluting the heme chromophore from hemoglobin. Direct transcardial perfusion of an aminoalcohol-containing cocktail that we previously termed CUBIC coupled with a 10 day to 2 week clearing protocol decolorized and rendered nearly transparent almost all organs of adult mice as well as the entire body of infant and adult mice. This CUBIC-perfusion protocol enables rapid whole-body and whole-organ imaging at single-cell resolution by using light-sheet fluorescent microscopy. The CUBIC protocol is also applicable to 3D pathology, anatomy, and immunohistochemistry of various organs. These results suggest that whole-body imaging of colorless tissues at high resolution will contribute to organism-level systems biology.

The separation of the enantiomers of phenylalanine amide and N-methyl derivatives as well as some amino alcohols was studied by CE in acidic BGEs using CDs as chiral selectors. The native CDs displayed only low chiral recognition ability at a concentration of 15 mg/mL in 20 mM sodium phosphate buffer, pH 2.5. In contrast, the analyte enantiomers were separated in the presence of randomly sulfated CDs under reversed polarity of the applied voltage. Sulfated β-CD proved to be the most universal selector resulting in the enantioseparation of all analytes. Opposite enantiomer migration order depending on the size of the CD cavity was observed for phenylalanine amide and 2-amino-2-phenylethanol. The R-enantiomers migrated first in the presence of sulfated α-CD and γ-CD while the S-enantiomers were detected first in the presence of sulfated β-CD. The enantioseparations could be rationalized based on analyte complexation by the respective CDs except for 2-amino-2-phenylethanol and sulfated β-CD where essentially equal complexation constants were derived for the enantiomers. In this case, the migration behavior could be attributed to the mobilities of the enantiomer-CD complexes adding another example to the CE-specific phenomenon of enantioseparations based primarily on complex mobilities., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of lanthanide tris(β-diketonates) functioned as useful chirality probes in the vibrational circular dichroism (VCD) characterization of biological amino alcohols. Various chiral amino alcohols induced intense VCD signals upon ternary complexation with racemic lanthanide tris(β-diketonates). The VCD signals observed around 1500 cm(-1) (β-diketonate IR absorption region) correlated well with the stereochemistry and enantiomeric purity of the targeted amino alcohol, while the corresponding monoalcohol, monoamine, and diol substrates induced very weak VCD signals. The high-coordination number and dynamic property of the lanthanide complex offer an effective chirality VCD probing of biological substrates., (© 2014 Wiley Periodicals, Inc.)

A tandem mass spectrometry method for high-sensitivity qualitative and quantitative discrimination of chiral amino compounds is conducted. The method is based on a chemical derivation process that uses a simple reagent, L-1-(phenylsulfonyl)pyrrolidine-carbonyl chloride, as the probe. The method is applicable in both organic solutions and biological conditions. Twenty-one pairs of enantiomer containing amino acids, amino alcohols, and amines are used to produce diastereomers using the probe via in situ reaction for 20 s at room temperature. The resulting diastereomers are successfully recognized based on the relative peak intensities of their fragments in positive mode, with the chiral recognition ability values ranging from 0.35 to 3.83. The L/D ratio of Pro spiked at different concentrations (enantiomeric excess) in both acetonitrile and dog plasma is determined by establishing calibration curves. This method achieves a lower limit of quantification of 50 pmol in analyzing amino acids using an extract ion chromatograph. The relative standard deviation for both qualitative and quantitative results is <5%. Thus, the present method is demonstrated as a new and practical technique of rapidly and sensitively determining enantiomers of amino compounds., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Capillary columns were packed firstly with silica modified-teicoplanin (teico-CSP) particles for a short zone (1-5 cm) and then with a Cogent Bidentate C18 silica phase (25 cm). The first part of the column (inlet) was intended for focusing the sample model, consisted of selected basic compounds, while the second zone, containing RP18 particles, was used for their separation. For method optimization, some important experimental parameters were studied including the sample solvent, injected volume and teico-CSP particles length. 3 cm teico-CSP resulted to be effective for the on-line pre-concentration, before the separation, of acebutolol, alprenolol, nadolol, oxprenolol and terbutaline with limit of detection at levels of few ng/mL. The comparison of the data obtained in absence of the chiral stationary phase revealed that the use of this chiral short sector into the capillary allowed the increase of the sensitivity of 5-12 times. Injection of larger sample volumes were easily done using higher length of the teico-CSP into the capillary, however the use of 5 cm length was not appropriate because caused the partial chiral separation of some studied compounds., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Liquid chromatographic resolution of racemic compounds containing a primary amino group has been known to be most successful when chiral crown ether-based chiral stationary phases (CSPs) are used. Among various crown ether-based CSPs, the stationary phase based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid covalently bonded to silica gel has been successfully applied in the resolution of various racemic compounds containing primary amino groups. In this chapter, the preparation of the CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid covalently bonded to silica gel and examples for the application to the enantioseparation of racemic compounds including α-amino acids, cyclic amines, amino alcohols, and chiral drugs are described.

Chiral ligand-exchange capillary electrophoresis is a relatively cheap and flexible format of capillary electrophoresis. It separates chiral analytes with a metal complex chiral selector that is composed of a metal ion and either homogeneous or heterogeneous chiral ligands (in respect of analytes). The analytes to be separated are required to possess the ability to coordinate with the metal ion, commonly containing N and/or O atoms, for example, amino acids or amino alcohols. In present chapter we take the separation of dansyl dl-amino acids as a key example to guide through the setup of a chiral ligand-exchange capillary electrophoresis enantioseparation protocol. The critical working conditions emphasized include the selection of metal ion, pH window, the ligand-to-metal ratio and/or the concentrations of the complex and electrolytes. In addition, trouble-shooting advice is given such as the way to overcome baseline drifting.

Plasmodium falciparum is the causative agent of malaria, a deadly infectious disease for which treatments are scarce and drug-resistant parasites are now increasingly found. A comprehensive method of identifying and quantifying metabolites of this intracellular parasite could expand the arsenal of tools to understand its biology, and be used to develop new treatments against the disease. Here, we present two methods based on liquid chromatography tandem mass spectrometry for reliable measurement of water-soluble metabolites involved in phospholipid biosynthesis, as well as several other metabolites that reflect the metabolic status of the parasite including amino acids, carboxylic acids, energy-related carbohydrates, and nucleotides. A total of 35 compounds was quantified. In the first method, polar compounds were retained by hydrophilic interaction chromatography (amino column) and detected in negative mode using succinic acid-(13)C(4) and fluorovaline as internal standards. In the second method, separations were carried out using reverse phase (C18) ion-pair liquid chromatography, with heptafluorobutyric acid as a volatile ion pairing reagent in positive detection mode, using d(9)-choline and 4-aminobutanol as internal standards. Standard curves were performed in P. falciparum-infected and uninfected red blood cells using standard addition method (r(2)>0.99). The intra- and inter-day accuracy and precision as well as the extraction recovery of each compound were determined. The lower limit of quantitation varied from 50pmol to 100fmol/3×10(7)cells. These methods were validated and successfully applied to determine intracellular concentrations of metabolites from uninfected host RBCs and isolated Plasmodium parasites., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A highly porous and fluorescent metal-organic framework (MOF), 1, was built from a chiral tetracarboxylate bridging ligand derived from 1,1'-bi-2-naphthol (BINOL) and a cadmium carboxylate infinite-chain secondary building unit. The fluorescence of 1 can be effectively quenched by amino alcohols via H-bonding with the binaphthol moieties decorating the MOF, leading to a remarkable chiral sensor for amino alcohols with greatly enhanced sensitivity and enantioselectivity over BINOL-based homogeneous systems. The higher detection sensitivity of 1 is due to a preconcentration effect by which the analytes are absorbed and concentrated inside the MOF channels, whereas the higher enantioselectivity of 1 is believed to result from enhanced chiral discrimination owing to the cavity confinement effect and the conformational rigidity of the BINOL groups in the framework. 1 was quenched by four chiral amino alcohols with unprecedentedly high Stern-Volmer constants of 490-31200 M(-1) and enantioselectivity ratios of 1.17-3.12.

A new colorimetric chiral sensor material consisting of three different functional sites such as chromophore (2,4-dinitrophenylazophenol dye), binding site (crown ether), and chiral barrier (3,3'-diphenyl-1,1'-binaphthyl group) was prepared and applied to the recognition of the two enantiomers of primary amino alcohols and amines. Among five primary amino alcohols and two primary amines tested, the two enantiomers of phenylalaninol show the highest difference in the absorption maximum wavelength (Δλ(max)=43.5 nm) and in the association constants (K(S)/K(R)=2.51) upon complexation with the colorimetric chiral sensor material and, consequently, the two enantiomers of phenylalaninol were clearly distinguished from each other by the color difference., (Copyright © 2010 Wiley-Liss, Inc.)

The case of a 13-month-old boy with a diagnosis of unclear unconsciousness is reported on. As the physical examination did not lead to any explanation of his condition, the administration of drugs in the context of Munchausen syndrome by proxy was suspected. Complex forensic-toxicological analyses using HPLC/UV, LC/MS/MS, and GC/MS identified ambroxol and clobutinol, two drugs that are indicated for acute respiratory diseases. No other central active compounds were detected. The accusation of intentional bodily injury raised against the parents could be rebutted, since the boy's unconsciousness could be explained with a rare but harmful side effect of the antitussive clobutinol.

Ten chiral derivatizing reagents (CDRs) were synthesized by replacing the L-Ala-NH(2) moiety in Marfey's reagent (MR) by seven L-amino acid amides and three L-amino acids employing microwave irradiation (MW) and were characterized. Ten racemic amino alcohols were derivatized with these CDRs under MW. The diastereomers were separated on a reversed-phase C(18) column using binary mixtures of acetonitrile with aqueous trifluoroacetic acid (TFA) and triethylammonium phosphate buffer (TEAP). In general, amino acid variants of MR provided better separation of diastereomers in comparison to amino acid amide variants. The method was also found successful for the separation of 20 diastereomers from a mixture.

The authors report on two cases of suspected Munchausen by proxy syndrome. In a 3-year-old boy, clinical toxicological analyses produced suspicious clues that an antidepressant had been administered, which could not be verified by forensic toxicological investigations. In a 13-month-old boy, the mother was also suspected of having poisoned the child. Initial clinical toxicological examinations failed to explain the observed symptoms (unclear unconsciousness, narrowed pupils). While in the first case, the incorrect interpretation of findings by a laboratory without forensic experience resulted in suspicions against the mother, the cause for the observed symptoms in the second case could be proved by complex analyses not performed before and the suspicion that the clinical picture had been intentionally brought about could be cleared up (use of an antitussive containing clobutinol). The two reports show that especially in cases with a potential forensic background, adequately qualified forensic laboratories with a broad spectrum of analytical methods should be involved.

The chirality of sec/prim- and prim/sec-1,2-amino alcohols can be determined by (1)H NMR of just one MPA derivative--either (R) or (S)--by comparison of two spectra at different temperatures and analysis of the evolution of the easily observable singles of the CalphaH signals.

The absolute configuration of sec/prim- and prim/sec-1,2-amino alcohols is determined by comparison of the (1)H NMR chemical shifts of the auxiliary OMe or CalphaH groups at the corresponding bis-( R) and bis-( S)-MPA derivatives. This is the first NMR method that allows the assignment of absolute configuration without resorting to the shifts of hydrogens at the substrate and is based on the cross anisotropic interactions between auxiliaries.

The analysis of nitrogen containing amino alcohols, which are the precursors and degradation products of nitrogen mustards and nerve agent VX, constitutes an important aspect for verifying the compliance to the CWC (Chemical Weapons Convention). This work devotes on the development of solid-phase extraction method using silica- and polymer-based SCX (strong cation-exchange) and MCX (mixed-mode strong cation-exchange) cartridges for N,N-dialkylaminoethane-2-ols and alkyl N,N-diethanolamines, from water. The extracted analytes were analyzed by GC-MS (gas chromatography-mass spectrometry) in the full scan and selected ion monitoring modes. The extraction efficiencies of SCX and MCX cartridges were compared, and results revealed that SCX performed better. Extraction parameters, such as loading capacity, extraction solvent, its volume, and washing solvent were optimized. Best recoveries were obtained using 2 mL methanol containing 10% NH(4)OH and limits of detection could be achieved up to 5 x 10(-3) microg mL(-1) in the selected ion monitoring mode and 0.01 microg mL(-1) in full scan mode. The method was successfully employed for the detection and identification of amino alcohol present in water sample sent by Organization for Prohibition of Chemical Weapons (OPCW) in the official proficiency tests. The method was also applied to extract the analytes from human plasma. The SCX cartridge showed good recoveries of amino alcohols from human plasma after protein precipitation.

Two types of secondary amino alcohols were successfully resolved on a liquid chromatographic chiral stationary phase based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. The secondary amino alcohols containing a secondary amino group connected directly to the stereogenic center were resolved much better than those containing a hydroxyl group attached directly to the stereogenic center. In addition, the dependence of the separation factor (alpha) on column temperature was exactly opposite for the two different types of secondary amino alcohols. From the thermodynamic calculations based on Van't Hoff plots, we conclude that the enantioselectivity for the resolution of the secondary amino alcohols containing a secondary amino group connected directly to the stereogenic center is enthalpically controlled while that for the resolution of the secondary amino alcohols containing a hydroxyl group attached directly to the stereogenic center is entropically controlled.

A liquid chromatographic chiral stationary phase (CSP) based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6, which has been utilized in the resolution of alpha-amino acids, amines and amino alcohols, was treated with excess of n-octyltriethoxysilane to prepare a new improved CSP. The residual silanol groups of the original CSP were protected by n-octyl groups in the new CSP. The chiral recognition ability of the new CSP was superior to that of the original CSP in the resolution of alpha-amino acids, amines and amino alcohols. Retention factors (k1) for the resolution of alpha-amino acids were lower on the new CSP than on the original CSP while those for the resolution of amines and amino alcohols were higher on the new CSP than on the original CSP. The improved chiral recognition ability of the new CSP and the retention behaviors of the two enantiomers on the new CSP have been rationalized to stem from the removal of the non-enantioselective interactions between the analytes and the residual silanol groups of the original CSP and the improved lipophilicity of the CSP.

A simple procedure for obtaining and purifying two degradation products of efavirenz (amino alcohol and quinoline derivatives) from drug substance hydrolysis is described. These impurities are known to exhibit very different UV absorbance properties from those of the parent compound, making determination using a quantitation factor (QF) inaccurate. The obtained hydrolysis products were characterized by physicochemical methods to assure identity, purity and strength. Quinoline derivative was of high purity degree (100%) and amino alcohol was 98.74% pure. Both were set as reference standards in chromatographic related compounds test for efavirenz drug substance and tablets analyses.

The applicability of (-)-myrtenal as a chiral derivatizing agent in combination with (13)C NMR spectroscopy was investigated. (13)C NMR was found to be a valuable tool for the identification and enantiomer differentiation of primary amines including beta-amino alcohols and vicinal diamines. The enantiomeric excess could be determined via automated deconvolution and integration, and was found to be in good accordance with the expected values even in the cases, when enantiomer differentiation was not possible in (1)H NMR spectra.

A practical UV-vis sensing method for enantioselective microanalysis of unprotected amino acids, amines, amino alcohols, and carboxylic acids in aqueous solution has been developed. Both concentration and enantiomeric composition of a wide range of chiral substrates can be determined with high accuracy by two simple competitive binding assays using a scandium complex derived from 1,8-bis(3-(3',5'-dimethylphenyl)-9-acridyl)naphthalene N,N'-dioxide.

In this work, a novel microextraction method termed polymer-coated hollow fiber microextraction (PC-HFME) was developed in combination with capillary electrophoresis (CE). Polar dihydroxylated polymethylmethacrylate polymer was coated onto a porous propylene hollow fiber membrane and used as an adsorbent and that was placed in a stirred aqueous sample solution. Tumbling of the extraction device within the sample solution facilitated extraction. The amino alcohols (2-amino-1-phenylethanol, norephedrine, alprenolol and atenolol which are beta-blocker drugs), were used as model compounds to investigate the extraction performance. No organic solvent was used in this procedure. The extract was then further concentrated through on-column stacking (normal stacking mode) during CE analysis. The detection limits ranged from 0.9 to 7 ng ml(-1). Relative standard deviations (n=6) ranged from 4 to 6%. The extraction of the amino alcohols in spiked wastewater effluent (representing a complex matrix) was evaluated using the developed procedure.

Metal working fluids (MWFs) are widely used as lubricants and coolants for different industrial operations. Biocides are ingredients of MWFs to control the microbial growth; derivatives of hexahydrotriazines and oxazolidines are generally used. Because of the lack of appropriate characterization, an existing capillary electrophoretic method for their quantification was improved. During the process of optimization, it became clear that hydrolysis products, derivatives of amino alcohols, severely interfere with the separation procedure. Since indirect-UV detection lacked the required selectivity, mass-selective detection was employed. NMR and MS established the absence of amino alcohols in the original educts. The aqueous solutions of the biocides stored for extended time remained amino alcohol-free, suggesting that these amino alcohols are formed from the biocides during the capillary electrophoretic separation. The observation of narrow and symmetric peaks indicated hydrolysis, and the polarity of the products implied favorable conditions for capillary electrophoretic separation. Methods were optimized for the analysis of the amino alcohols, the hydrolytic products of the formaldehyde releasers, using indirect-UV and MS detection. This method was extended to other likely solutes used as alkaline-reserve ingredients. The analytes were separated within 9 min with a high precision of migration times (the RSDs were below 1.5%). When quantifying from mobility scale, the calibration curves produced linearity with regression coefficients in the range of 0.990-0.999. The detection limit was lower than 1 mg/L in the case of MS detection. The influence of water-based MWF was also investigated, and no matrix effect on the migration of the analytes and on the peak areas was observed.

Nitrogen-containing chemicals are one of the important families of compounds relevant to the purposes of the Chemical Weapons Convention (CWC). Several applications, using various injection modes, of new deactivated columns specially designed for basic compounds are presented. These columns prove remarkably well-suited to the gas chromatographic (GC) analysis of the chemicals of interest, even to underivatized amino-alcohols, whose analysis on conventional GC columns is often difficult and hindered by poor resolution and high detection limits. Such a deactivated phase can even replace the typical GC phases used for CWC verification purposes.

Novel N-acylated-(S)-cysteine derivative-N-(R)-mandelyl-(S)-cysteine (R-NMC), containing additional chiral center, aromatic and polar alpha-substituents in contrast to the traditionally used enantiomerically pure thiols, has been demonstrated to be an efficient SH-reagent for enantiomeric HPLC analysis of primary nonfunctionalized amines and amino alcohols after precolumn derivatization with o-phthalaldehyde. The R-NMC-derived isoindoles as well as adducts formed using traditional SH-reagents had a characteristic absorption maximum at 340 nm with a molar absorbance 6000 M(-1) cm(-1), were stable during the HPLC-analysis and highly fluorescent allowing to detect 1 fmol of amino compound. Using diastereomeric R-NMC all tested amino alcohols were resolved effectively as well as nonfunctionalized amines, some of which were not resolved by a direct method on a chiral phase. Applying traditional enantiomeric N-acetyl-(S)-cysteine (NAC) only some isoindoles formed by aliphatic amino alcohols have been separated satisfactorily. The enhanced selectivity for R-NMC-derived isomers has been achieved, obviously, due to the involvement of the substituents at an extra chiral center into additional intramolecular interactions.

Various techniques, namely differential scanning calorimetry, optical microscopy, dielectric and Raman spectroscopy, all covering a wide range of temperatures, were used to study the thermodynamically stable phases and molecular mobility of crystals of long chain 2-amino alcohols. The results showed that two different crystal forms are present in each sample. The temperature behaviour of the phases is studied in details.

There are a number of situations where there is a need to determine the concentrations of components in solid-state mixtures without dissolving the sample. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) coupled with partial-least-squares (PLS) data analysis has been used to determine the minor component in a mixture of structurally similar solid-state compounds, in this case mixtures of ephedrine and pseudoephedrine. Factors that limit the precision and accuracy of the determinations are discussed. It is shown that when care is taken to produce homogeneous calibration samples very good results can be obtained, in this case cross-validated standard error of predictions of 0.74 wt% when the minor component spanned the concentration range of 0-50 wt%, and 0.11 wt% when the minor component spanned the concentration range of 0-5 wt%. Results are presented that indicate that the amount of data available to the PLS calibration routine relative to the range over which the calibration is performed can limit the precision and accuracy of the determinations.

N-Phenylacetyl-(R)-phenylglycyl-(S)-cysteine (NPPC) was used for the determination of enantiomers of primary amines by rpHPLC with a precolumn modification with o-phthalaldehyde. NPPC was compared with the classic SH reagent N-acetyl-(S)-cysteine (NAC) in the analysis of stereomers of nonfunctionalized amines and amino alcohols. After the NAC modification, the resulting diastereomeric isoindoles were difficult to separate by HPLC, and satisfactory resolution was achieved only for some aliphatic amino alcohols. The use of NPPC improved the chromatographic analysis of stereomeric amino alcohols and, in addition, allowed the enantiomeric analysis of the nonfunctionalized amines. Similarity between the side radicals of the amino component and the thiol reagent favored the diastereomer separation. This method was used for determination of the absolute concentration of individual enantiomers of amines in the course of stereoselective enzymatic reactions. The optically active NPPC was prepared with a high yield by a chemoenzymatic synthesis based on a regioselective acylation of the (S)-cysteine amino group in aqueous medium by the action of penicillin acylase. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.

Selected reaction monitoring (SRM) with electrospray ionization was used as a specific detection technique for the analysis of alkanolamines in plant tissue extracts. Ion-exchange chromatography was used as the method of separation. Quantification was based on monitoring the loss of either H2O or 2(H2O) from the protonated molecule [M+H]+. The method provided increased selectivity for all analytes and better detection limits for three of the six analytes investigated compared with an earlier method using selected ion monitoring with liquid chromatography. Instrumental detection limits ranged from 6-300 pg injected for monoethanolamine (MEA), monoisopropanolamine (MIPA), diethanolamine (DEA), methyldiethanolamine (MDEA), diisopropanolamine (DIPA), and triethanolamine (TEA). Method robustness and selectivity were demonstrated by the determination of DIPA and a known transformation product MIPA in over 35 plant extract samples derived from a laboratory study of plant uptake mechanisms., (Copyright 2004 John Wiley and Sons, Ltd.)

Ion suppression is a well-known phenomenon in electrospray ionization (ESI) mass spectrometry. These suppression effects have been shown to adversely affect the accuracy and precision of quantitative bioanalytical methods using ion spray. Such suppression effects have not been as well defined in atmospheric pressure chemical ionization (APCI) and there is some debate whether these effects actually occur in the ionization process using APCI. Here an example is described where clear ion suppression was observed during studies on a model compound and three metabolites using APCI liquid chromatography/tandem mass spectrometry (LC/MS/MS)., (Copyright 2004 John Wiley & Sons, Ltd.)

The use of L-(+)-tartaric acid as a chiral mobile phase additive (CMPA) has been investigated in a packed-column SFC system. The CMPA, carbon dioxide, and methanol, containing a high concentration of aliphatic amine additive, were used as the mobile phase and Hypercarb as support [Gyllenhaal O., Karlsson A., SFC of metoprolol and other amino alcohols on Hypercarb (in preparation)]. Good enantioselectivities were obtained for tertiary amine homologues of 2-amino alcohols, used as beta-adrenoreceptor-blocking drugs. Moderate selectivities were observed for aromatic compounds having a second substituent in the ortho-position. The overall retention was influenced by the aromaticity of the analytes as well as the presence of free electron pairs in the molecule. Increased concentrations of CMPA gave higher retention and also increased the enantioselectivity. The practical utility of this present enantioselective system was demonstrated on one batch of (S)-metoprolol that was N-methylated with methyl iodide. The enantiomeric separation was accomplished within 10 min., (Copyright 2002 Elsevier Science B.V.)

The readily available N-Boc-protected delta-amino alpha,beta-unsaturated gamma-keto ester 1 was diastereoselectively reduced to the corresponding alcohols 2 and 3, using boron- and aluminum-based reducing reagents. Reduction reactions were successful and resulted in anti/syn ratios of alcohols of >95:5 (80% yield), using LiAlH(O-t-Bu)(3) in EtOH at -78 degrees C under chelation control, and 5:95 (98% yield), using NB-Enantride in THF at -78 degrees C under Felkin-Anh control.

We described a new method for the enrichment of basic drugs present in water samples via liquid-phase microextraction (LPME) combined with on-column stacking in capillary electrophoresis. Two steps were employed to enhance the detection sensitivity of four amino alcohols. The analytes were first extracted from aqueous sample (donor solution) that were adjusted to basic through a thin layer of 1-octanol entrapped within the pores of a polypropylene hollow fiber, and then into a 5-microl acidic acceptor solution inside the hollow fiber. The extract was then further enriched through on-column stacking in capillary electrophoresis. With this two-step enrichment procedure, the method provided 72-110-fold preconcentration of the target amino alcohols. The limits of detection were 0.08-0.5 microg/ml. Relative standard deviation (n=6) ranged between 4.3 and 6.9% for the studied drugs utilizing 2-amino-1-phenylethanol as internal standard. The extraction of amino alcohols in spiked urine samples was evaluated using the developed procedure.

Box-Behnken experimental designs do not appear to be extensively used in optimisation of analytical methods using capillary electrophoresis (CE). This paper describes the use of the Box-Behnken experimental design to optimise the factors affecting the separation of ethambutol hydrochloride (EB), its impurity 2-amino-1-butanol and the internal standard (phenylephrine hydrochloride) in a CE method for a pharmaceutical tablet assay. The three factors studied simultaneously were: buffer pH, buffer concentration and applied electric field, each at three levels. The method was optimised with respect to three responses: resolution between peaks, theoretical plate count and the migration time of the EB peak. A statistical programme, which applies a multiple response optimisation algorithm, was used to calculate and optimise the three responses simultaneously. The optimum conditions were established to be 58.0 mM sodium borate buffer at pH 9.50 and an applied electric field of 412 V/cm. The robustness of the method was also determined and confirmed using a second Box-Behnken design, as part of the validation exercise. System suitability values for the method were derived from the regression surface analysis. The CE method for a pharmaceutical tablet formulation was further validated according to current regulatory requirements, with respect to linearity and range, precision, specificity, accuracy and limit of quantitation. The optimised method gives a fast and efficient separation under 4 min, with complete resolution between the three peaks, and represents an improvement over the existing USP method. It can be concluded that the Box-Behnken experimental design provides a suitable means of optimising and testing the robustness of a CE pharmaceutical method.

A dramatic enhancement in fluorescence intensity from 1,1'-bi-2-naphthol (BINOL) to dendritic phenyleneethynylenes containing the BINOL core was observed. The strong fluorescence of the dendrimers allows a very small amount of the chiral materials to be used for sensing. The light harvesting antennas of the dendrimer funnel energy to the center BINOL unit, whose hydroxyl groups upon interaction with a quencher molecule lead to fluorescence quenching. This mechanism makes the dendrimers have much more sensitive fluorescence responses than corresponding small molecule sensors. The fluorescence of these dendrimers can be enantioselectively quenched by chiral amino alcohols. It is observed that the fluorescence lifetime of the generation two dendrimer does not change in the presence of various concentrations of 2-amino-3-phenyl-1-propanol. This demonstrates that the fluorescence quenching is entirely due to static quenching. Thus, formation of nonfluorescent ground-state hydrogen-bond complexes between the dendrimers and amino alcohols is proposed to account for the fluorescent quenching. A linear relationship has been established between the Stern-Völmer constant of the generation two dendrimer and the enantiomeric composition of 2-amino-3-phenyl-1-propanol. Such enantioselective fluorescent sensors may allow a rapid determination of the enantiomeric composition of chiral molecules and are potentially useful in the combinatorial search of asymmetric catalysts and reagents.

A method for determining the enantiomers of 10 therapeutically relevant aminoalcohols using HPLC and precolumn derivatization was developed. Naphthyl isocyanate reacted with racemic aminoalcohols to form urea derivatives which were separated isocratically on a cellulose tris(3,5-dimethylphenylcarbamate) coated silica gel column, and detected fluorometrically in the lower ng mL(-1) range. The effluents can also be monitored at lower sensitivity, using an ultraviolet detector operated at 220 nm., (Copyright 2001 John Wiley & Sons, Ltd.)

The ion mobility (IMS) spectra of the alkanolamines, monoethanolamine (MEA), 3-amino-1-propanol (PRA), 4-amino-1-butanol (BUA), and 5-amino-1-pentanol (PEA) with acetone and 4-heptanone reagent gases have been measured using a hand-held spectrometer. Monomer and dimer peak patterns were observed for all the alkanolamines with acetone reagent gas. Drift times of monomer and dimer ion clusters for each alkanolamine increased linearly in order of size of alkyl group. Ammonia, Freon 22, and F76 diesel vapors, having similar or coincident mobilities, caused severe interference. Replacement of acetone with 4-heptanone reagent gas resulted in good separation by the altering drift times of product ions. The limit of detection was 0.005 ppm having a linear range of 0.005-0.7 ppm, and signal saturation occurred above 0.88 ppm. Detection was reversible, with a response time of 4 min and a slower recovery time of > 60 min, at vapor levels of 0.7 ppm and ambient nozzle and drift-region temperatures. In contrast to acetone chemistry, single-peak patterns were observed for the alkanolamines with the 4-heptanone reagent. Further, drift times unexpectedly remained stagnant with increasing alkyl-group size. From atmospheric pressure chemical ionization (APcI) tandem mass spectral identifications and collision induced studies, dynamic changes in product-ion equilibria in the IMS drift region compensated by differences in collision cross sections were suggested as the governing causes of the unusual mobility effect.

A non-chiral crown ether (18-crown-6) along with beta-cyclodextrin (beta-CD) was used to achieve enantioselective separations of primary amino compounds in capillary electrophoresis. In this new method, the amino group of these compounds is protonated in a low pH separation buffer and forms a selective host-guest complex with the crown ether (amino compound+18-crown-6). The hydrophobic portion of the host-guest complex is then incorporated into the cavity of the beta-cyclodextrin. The amino compound is sandwiched between the crown ether and the cyclodextrin (18-crown-6+amino compound+beta-CD) and thus determines or enhances the enantioselective recognition. It is postulated that the formation of this sandwich results in a more selective chiral interaction between the molecule and beta-cyclodextrin. The chiral recognition is dependent upon the formation of this sandwich complex. This method has been used to achieve enantioselectivity of primary amino compounds with a wide variety of substitutions.