• YAKHAK HOEJI
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• v.53 no.2
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• pp.60-68
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• 2009

In terms of chiral issue, two enantiomers of chiral drugs often differ significantly in their pharmacological, toxicological and pharmacokinetic profile. Chiral switches of racemic drugs have been redeveloped as single enantiomers. Several chiral resolution techniques in chirotechnology are introduced and the most used chiral HPLC chromatographic method among several chiral analysis techniques is described with its several advantages. Several types of chiral HPLC columns derived from their chiral selectors are discussed with their property and applications for enantiomer separation.

• Journal of Pharmaceutical Investigation
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• v.35 no.1
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• pp.57-63
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• 2005

Numerous drugs are chiral because they possess one or more chiral centers. Enantiomers may differ in their pharmacokinetic, pharmacological and toxicological properties. However, the significance of stereochemistry of drugs in their therapeutic uses has received relatively little attention until recently. The US FDA issued a guideline on stereoisomeric drugs in 1992, and the European agency describes tests for new drug substances which are optically active in an ICH(International Conference of Harmonization) guideline. According to the guidance, enantiomers may differ in their pharmacokinetic, pharmacological and toxicological properties. Therefore, in this paper, we examined the recently published Canadian guidance, stereochemical issues in chiral drug development, which will be references to make a guidance on stereochemical issues in chiral drug development in Korea.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.250.2-251
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• 2000

• Archives of Pharmacal Research
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• v.27 no.10
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• pp.1009-1015
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• 2004

Quantitative Structure-Resolution Relationship (QSRR) using the Comparative Molecular Field Analysis (CoMFA) software was applied to predict the chromatographic behaviors of chiral drugs with an amine moiety on the chiral cellobiohydrolase (CBH) columns. As a result of the Quantitative CoMFA-Resolution Relationship study, using the partial least square method, prediction of the behavior of drugs with amine moiety upon chiral separation became possible from their three dimensional molecular structures. When a mixed mobile phase of 10 mM aqueous phosphate buffer (pH 7.0) - isopropanol (95 : 5) was employed, the best Quantitative CoMFA-Resolution Relationship, derived from the study, provided a cross-validated $q^2$ = 0.933, a normal $r^2$ = 0.995, while the best Quantitative CoMFA-Separation Factor Relationship, also derived from the study, yielded a cross-validated $q^2$ = 0.939, a normal $r^2$ = 0.991. When all of these results are considered, this QSRR-CoMFA analysis appears to be a very useful tool for the preliminary prediction on the chromatographic behaviors of drugs with an amine moiety inside chiral CBH columns.

• Archives of Pharmacal Research
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• v.23 no.2
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• pp.178-181
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• 2000

In order to study the simultaneous determination of (+)- and (-)-cetirizine in human urine we have developed a chiral separation method by HPLC. A chiral stationary phase of $\alpha$$_1$-acidglycoprotein, the AGP-CSP was used to separate the enantiomers. The pH of the phosphate buffer, as well as the content of the organic modifier in the mobile phase, markedly affected the chromatographic separation of (+)- and (-)-cetirizine. A mobile phase of 10 m㏖/1 phosphate buffer (pH 7.0)-acetonitrile (95 : 5, v/v) was used for the urine assays. Ultraviolet absorption was monitored at 230nm and roxatidine was employed as the internal standard for quantification. (+)-Cetirizine, (-)-cetirizine and the internal standard were eluted at retention times of 12, 16, and 32 mins, respectively. The detection limit for cetirizine enantiomers was 400 ng/$m\ell$ of urine. A pharmacokinetic study was conducted with the help of 5 healthy female volunteers who were administered with a single oral dose of racemic cetirizine (20 mg). The peak area ratios provided by the cetirizine enantiomers were linear(r>0.997) over a concentration range of 2.5-200 ${\mu}g/ml$. The peak of the excreted cetirizine enantiomers appeared in the urine sample during the period of 1-2 hrs following the administration of the oral dose. The excreted level of (+)-cetirizine was slightly higher than (-)-cetirizine but the difference was not statistically significant. However, this method appears to have applications for enantioselective pharmacokinetic studies of racemic drugs.

• Clean Technology
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• v.22 no.2
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• pp.75-81
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• 2016

As the quality of life has improved, the desire for the safety and quality of the foods and drugs has been gradually increasing. For safety and quality management in foods, drugs, health management, agriculture, environmental conservation, and the industrial fields, the demand for quickly and accurately measuring various chemicals has been increasing. As well, the desire for self-diagnosis of one's own health state and self-examining the safety of environment has been gradually increasing. Optical Isomers can have very different physiological effects on human beings. One isomer can exhibit desirable pharmacological, pharmacodynamic, pharmacokinetic and physiological properties, while the other isomer can exhibit undesirable and toxic properties toward living organisms, especially human beings. And they can exhibit different activities in chemical and biotechnological processes. Although the majority of commercially available drugs are now both synthetic and chiral materials, a most chiral drugs are still marketed as racemic drugs. Thus, to avoid possible undesirable side effects from chiral drugs, more effective methods for separating and recognizing chiral compounds are urgently needed. In this report, we investigated the overall developing trends of the chiral drug separation and analysis technology by using molecular recognition.

• Mass Spectrometry Letters
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• v.10 no.1
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• pp.1-10
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• 2019

Amphetamine-type stimulants (ATS) are a group of ${\beta}$-phenethylamine derivatives that produce central nervous system stimulants effects. The representative ATS are methamphetamine and 3, 4-methylenedioxymethamphetamine (MDMA), and abuse of ATS has become a global problem. Methamphetamine is abused in North America and Asia, while amphetamine and 3, 4-methyle nedioxym ethamphetamine (Ecstasy) are abused in Europe and Australia. Methamphetamine is also the most abused drug in Korea. In addition to the conventional ATS, new psychoactive substances (NPS) including phenethylamines and synthetic cathinones, which have similar effects and chemical structure to ATS, continue to spread to the global market since 2009, and more than 739 NPS have been identified. For the analysis of ATS, two tests that have different theoretical principles have to be conducted, and screening tests by immunoassay and confirmatory tests using GC/MS or LC/MS are the global standard methods. As most ATS have a chiral center, enantiomer separation is an important point in forensic analysis, and it can be conducted using chiral derivatization reagents or chiral columns. In order to respond to the growing drug crime, it is necessary to develop a fast and efficient analytical method.

• KSBB Journal
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• v.27 no.4
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• pp.232-236
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• 2012

Comparative liquid chromatographic enantiomer separation of ${\alpha}$-amino acids, their esters and primary amino compounds was performed using two chiral stationary phases (CSPs) prepared by covalently bonding (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (18-C-6-TA) of the same chiral selector. In general, the separation factors and resolution factors for these analytes on CSP 1 were greater than on CSP 2, while these capacity factors on CSP 2 were quite greater than on CSP 1. Except for leucine methyl ester and phenylalanine methyl ester, the elution orders of all analytes including ${\alpha}$-amino ${\alpha}$-alkyl acids and phenylglycine alkyl esters on CSP 1 are identical to those on CSP 2. This study showed that different connecting structures for these two CSPs might influence their ability to resolve the analytes depending on their structures related to the chiral recognition mechanism.

• Analytical Science and Technology
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• v.24 no.5
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• pp.360-367
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• 2011

Optical purities of 10 commercialized naproxens prepared from eight Korean drug companies were examined by an optimized chiral HPLC condition. The Chiralcel OD-H column and ChiralHyun-LE(S)-1 column were used as chiral stationary phases and the mixed eluent of hexane/isopropanol/acetic acid as 100:2.85:0.1 was used as a mobile phase for effective enantioseparation. Optical purity values of most samples were higher than 97 percents, only one of them was about 95 percents. The average relative standard deviation of them appeared very small (0.034%).

• KSBB Journal
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• v.28 no.6
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• pp.423-427
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• 2013

A new convenient derivatization method of ${\alpha}$-amino acid esters as nitrobenzoxadiazole (NBD) derivatives for chiral resolution was introduced and the enantiomer separation of ${\alpha}$-amino acid esters as NBD derivatives was performed by normal HPLC using chiral columns based on polysaccharide derivatives. The NBD derivatives were readily prepared by stirring NBD-Cl and ${\alpha}$-amino acid methyl ester HCl with $NaHCO_3$ in ethanol. The performance of Chiralpak IA was superior to the other chiral stationary phases for enantiomer resolution of NBD derivatives of several ${\alpha}$-amino acid methyl esters. Owing to fluorescence detection as well as strong UV absorption, it is expected that the convenient analytical method developed in this study will be very useful for enantiomer separation of ${\alpha}$-amino acid esters as NBD derivatives on polysaccharide-derived chiral columns.