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Thirteen isoflavones were separated and purified from an ethanol extract of the rhizome of Dalbergia benthamii Prain by using silica gel, Sephadex LH-20, recrystallization et al. Their structures were identified by physicochemical properties and spectral analysis such as MS, 1D/2D-NMR as dalbergibenthamin (1), butesuperin A (2), xanthocercin A (3), butesuperin B (4), di-O-methylalpinum isoflavone (5), 2′-deoxgisoaunculutin (6), robustone (7), 4′-hydroxy-5,7-dimethoxy-6-(3-methyl-2-butenyl)-isoflavone (8), formononetin (9), 6″-O-rhamnosyldaidzin (10), 3′,4′-di-O-methylene-5-hydroxy-7-methoxy-6-isopentenyl isoflavone (11), derrubone dimethyl enter (12), and derrubone (13). Compound 1 is a pair of new isoflavonoid enantiomers, compound 12 is a new natural product and compounds 1-7 and 10-13 were obtained from D. benthamii Prain for the first time. In vitro cytotoxic activities of the compounds were explored by MTS testing with HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines. Results show that compound 8 significantly inhibited cellular proliferation. The IC50 of compound 8 in A-549 and SW480 cells was 16.68 ± 0.19 and 15.21 ± 0.60 μmol·L-1.
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Ten compounds were isolated from the 95% ethanol extract of the whole plant of Gerbera piloselloides by silica gel column chromatography, MCI column chromatography and semi-preparative HPLC methods. Their structures were identified on the basis of physicochemical properties, spectral data (UV, IR, MS and NMR), circular dichroism (CD) spectra and single crystal X-ray diffraction analysis as 3′R-gerpilosecoumarin A (1a), 3′S-gerpilosecoumarin A (1b), gymnastone (2), gerberinside (3), divaricataester C (4), luteolin (5), caffeic acid methyl ester (6), ethyl chlorogenate (7), 6-(β-D-glucopyranosyloxy)-7-methoxy-5-benzoranpropanoic acid methyl ester (8) and glucozaluzanin C (9). Among them, new compounds 1a and 1b were new compounds and optical enantiomers, which were obtained by chiral resolution, and their absolute configurations were determined by quantum chemical calculation ECD. Compounds 1 and 1a/1b significantly increased the survival of IEC-6 in rat small intestinal crypt epithelial cells after LPS injury.
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In Korea and China, ilaprazole is a widely used proton pump inhibitor in the treatment of gastric ulcers. In this study, a specific and sensitive LC-MS/MS method has been developed and validated for the quantification of ilaprazole enantiomers in the rat plasma, using R-lansoprazole as the internal standard. The enantioseparation was achieved on a CHIRALPAK AS-RH column (4.6 mm × 150 mm, i.d. 5μm), with a mobile phase composed of 10 mM ammonium acetate aqueous solution and acetonitrile (60:40, V/V), at a flow-rate of 0.5 mL/min. The method was validated over the concentration range of 0.5-300 ng/mL for both, R- and S -ilaprazole. The lower limit of quantification was 0.5 ng/mL for both enantiomers. The relative standard deviation (RSD) of intra- and inter-day precision of R-ilaprazole and S-ilaprazole was less than 10.9％, and the relative error accuracy (RE) ranged from -0.5％-2.0％. Finally, the method was successfully evaluated in rats in a stereoselective pharmacokinetic study of the ilaprazole racemate.
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Methamphetamine （MAMP） is a kind of amphetamine-type stimulants （ATS） which contains one chiral carbon atom in its structure. Therefore a pair of enantiomers, S-（+）-MAMP and R-（-）-MAMP exist. R type and S type methamphetamines possess similar physicochemical properties, but has largely different pharmacological and toxic effects. S-（+）-MAMP is the main component of addictive drug "Ice" at present, seriously affecting human health and public safety. The separation analysis and mechanism of toxic effects discussions on MAMP are the current research focuses. This paper reviews the research progress of separation analysis methods and toxic effects of methamphetamine enantiomers to provide reference for forensic study and forensic practice.
Subject(s)
Humans , Central Nervous System Stimulants , Methamphetamine/chemistry , Stereoisomerism , Substance Abuse DetectionABSTRACT
Four new octadecanoid derivatives (1-4) including a pair of enantiomers (1/2), along with 12 known analogues (5-16), were isolatedfrom the seeds of Ipomoea nil. Their structures were determined by detailed spectroscopic analyses and comparison with reported data of structurally related compounds, with the absolute configurations of 1 and 2 being assigned by an in situ dimolybdenum ECD method. Our bioassays revealed that these isolates did not show ABTS radical scavenging activity while 10 and 13 displayed better α-glucosidase inhibitory activity than the positive control acarbose (IC 167.7 ± 1.55 μmol·L), with IC of 92.73 ± 3.12 and 11.39 ± 2.18μmol·L, respectively.
Subject(s)
Fatty Acids , Chemistry , Metabolism , Glycoside Hydrolase Inhibitors , Chemistry , Metabolism , Inhibitory Concentration 50 , Ipomoea nil , Chemistry , Molecular Structure , Plant Extracts , Chemistry , Metabolism , Seeds , ChemistryABSTRACT
OBJECTIVE: To develop a supercritical fluid chromatography method for the separation of atorvastatin calcium and its enantiomer, meanwhile assaying the enantiomer. METHODS: Atorvastatin calcium and its enantiomer were separated on a ACQUITY UPC2 Trefoil CEL2 column(3.0 mm×150 mm, 2.5 μm) maintained at 45 ℃ with the mobile phase containing a mixture of CO2 and methanol with 0.1% TFA(78∶22, V/V) at 1.5 mL·min-1, and the detection wavelength was set at 244 nm. The back pressure was set at 13.8 MPa. RESULTS: The enantiomer and atorvastatin calcium were separated successfully in 5 min with a resolution factor of 4.1. Good linear relationship was established between the peak response and the concentration in the range of 2.5-50 μg·mL-1 for enantiomer(r2=0.999 9, n=6), the quantitative limit(S/N=10) was 2.5 μg·mL-1, and the detection limit(S/N=3) was 1.0 μg·mL-1. The spiked recovery of the enantiomer was 100.40%(n=9). CONCLUSION: The proposed method shows high accuracy, repeatability and stability. It can be employed for the quality control and stability research of the enantiomer of atorvastatin calcium.
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Currently, most commercially available antidepres-sants have one or more chiral centers,and development of chiral antidepressants are of great interest for researchers. Thalidomide induced tragedy promotes drug evaluation centers from various countries to reevaluate their current guidelines and recommend single enantiomer application when developing a chiral antide-pressant. Unfortunately,as far to our knowledge,traditional en-antiomers comparison and active enantiomer selection are real-ized by simple comparison using in vitro targets data. Our team established an integrated system for chiral antidepressant evalua-tion and active enantiomer screening based on four modules,in-cluding pharmacodynamic comparison,pharmacokinetic compar-ison, toxicological comparison, and comprehensive factors. Here,we review this integrated system and make a detailed a-nalysis taking ammoxetine as a realistic example.
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The study aims to establish an LC-MS/MS method for the determination of S-(+)-ibuprofen (S-IBP) and R-(-)-ibuprofen (R-IBP), which may be used subsequently to investigate the pharmacokinetics of ibuprofen enantiomers in healthy Chinese volunteers. Naproxen was used as an internal standard. The separation was achieved on a Chiralpak AD-3R column (4.6 mm×150 mm, 3.0 μm) with a mobile phase consisting of acetonitrile/0.01% formic acid aqueous solution (40:60) at a flow rate of 750 μL·min-1 within 23.0 min. Naproxen and the internal standard were measured by a triple-quadrupole mass spectrometer in negative electron electronic spray ion (ESI) mode using multiple reaction monitoring (MRM). The extracted ions monitored following MRM transitions were m/z 205.1→161.0 for ibuprofen enantiomers and m/z 229.1→185.0 for the internal standard naproxen. Plasma samples were pretreated through methanol precipitation. The calibration curve of S-IBP and R-IBP in human plasma was linear over the concentration rang of (0.05-30.00) μg·mL-1. The lower limit of quantitation was 0.05 μg·mL-1. The intra-and inter-run precisions of S-IBP at three quality control levels were within 2.2%-4.2%, the relative deviation of the assay was within -12.0%-13.0%. The intra-and inter-run precisions of R-IBP at three quality control levels were within 2.0%-8.2%, the relative deviation of the assay was within -11.5%-10.6%. The plasma samples were stable at room temperature (25℃) for 6 h, at -30℃ for 47 days and during three freeze-thaw cycles. The method was proved to be convenient, accurate and sensitive, and suitable for the pharmacokinetics study of ibuprofen enantiomers in healthy Chinese volunteers after a single oral dose of 300 mg ibuprofen extended-release capsule.
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Objective:To establish an HPLC method for the determination of optical isomers in carfilzomib .Methods:The sample was separated on a Chiralpak OX-H column.The mobile phase consisted of n-hexane∶isopropanol∶alcohol (89 ∶5 ∶6, v/v/v) with a flow rat of 1.0 ml· min-1 .The detection wavelength was 220 nm.Results:The linear rang of enantiomer , diastereomer Ⅰand di-astereomer Ⅱwas 0.54-2.14 μg· ml -1,0.11-1.80 μg· ml-1 and 0.11-1.81 μg· ml-1(r≥0.998), respectively.The lower limit of quantification was 0.07-0.27 μg· ml-1 .The recoveries of optical isomers were within the range of 99.6%-100.9% with RSD of 1.13%-1.59%(n=9).Conclusion:The method is sensitive, simple, fast, accurate and specific, and suitable for the study of opti-cal isomers in carfilzomib .
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Objective: To establish a determination method for the enantiomer in safinamide mesilate. Methods: A Chiralpak ASH (250 mm ×4. 6 mm, 5 μm) column was used with the mobile phase of n-hexane-ethanol-diethylamine (75 ∶ 25 ∶ 0. 1). The flow rate was 1. 0 ml·min-1 . The wavelength was set at 225 nm. The column temperature was 35℃. Results: The resolution of safinamide mesilate and the enantiomer was above 2. 0. The linear range of them was 1. 007-2 517. 500 μg·ml-1 and 0. 909-2273. 200 μg·ml-1 ,respectively(r = 0. 999 0). The average recovery of the enantionmer was 104. 9% with RSD of 2. 3% (n = 9). Conclusion: The method is accurate and rapid, and suitable for the determination of the enantiomer in safinamide mesilate.
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Objective:To establish a method for the separation and determination of ketoprofen enantiomer .Methods:A pre-col-umn derivation RP-HPLC method was used with L-alanine-β-naphthylamine ( L-Ala-β-NA) as the derivation reagent .The RP-HPLC conditions were as follows: a Hypersil ODS-2 column (250 mm ×4.6 mm,5 μm) was applied, the mobile phase was acetonitrile-0.025 mol· L-1 phosphate buffer solution (40∶60, v/v) and the flow rate was 1.0 ml· min-1 , the detection wavelength was set at 245 nm and the column temperature was 25℃.The injection volume was 10μl.Results:Base line separation was achieved for the sep-aration of enantiomer from ketoprofen , and the retention time for S-(+) -ketoprofen and the R-(-) -ketoprofen was 24.2 min and 26.0 min, respectively.Dexketoprofen within the range of 0.025-0.125 mg had a good linear relationship (r=0.998 1) and the aver-age recovery was 90.93%(RSD =4.10%, n=9 ).Conclusion:The method is simple, accurate and reliable, which can be applied in the separation and determination of ketoprofen .
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Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(-)-1 and (+)-1], phaitanthrin A and epiphaitanthrin A [(-)-2 and (+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(-)-3 and (+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column. Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism (ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A [(-)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products.
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OBJECTIVE: To establish a high performance liquid chromatographic method for chiral separation of levofloxacin-N-oxide enantiomers and purity test of the bulk drug. METHODS: The analysis was carried out on a C18 column with D-phenylalanine-copper sulfate solution-methanol (80:20) as mobile phase. The flow rate was 1.0 mL · min-1, the UV detection wavelength was set at 325 nm, and the column temperature was maintained at 40℃. RESULTS: A baseline separation of levofloxacin-N-oxide enantiomers was achieved and the resolution was 3.2 between the enantiomers under the above chromatographic conditions. CONCLUSION: This method is simple, rapid, and reproducible, and it can be used for the separation and purity test of levofloxacin-N-oxide.
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OBJECTIVE: To develop an isocratic supercritical fluid chromatography method for the separation of ezetimibe and its R-enantiomer. METHODS: Ezetimibe and its R-enantiomer were separated on a Chiralcel OD column (4.6 mm × 250 mm, 10 μm) maitained at 35℃ with the mobile phase containing a mixture of CO2 and methanol with 0.1% TFA-0.1% TEA (90:10, V/V) at 3.0 mL · min-1, and the detection wavelength was set at 235 nm. The back pressure of SF-CO2 was set at 15 MPa. RESULTS: The R-enantiomer and ezetimibe were separated successfully in 15 min with a resolution factor of 1.6. Good linear relationships were established between the peak response and the concentration in the range of 0.010-0.100 mg · mL-1 for each analyte(r =0.999 9 and 0.999 9, respectively, n =7), the quantitation limits (S/N = 10) were 34 and 32 ng, and the detection limits (S/N =3) were 10 and 9 ng, respectively. The spiked recovery of R-enantiomer of ezetimibe was 98.4% (n =9). CONCLUSION: The proposed method shows high accuracy, repeatability and stability. It could be employed for the quality control and stability research of R-enantiomer of ezetimibe and its tablet formulation.
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An enantioselective method was developed for the separation and determination of three chiral hexabromocyclododecanes ( HBCDs ) including α-HBCD, β-HBCD, γ-HBCD in soil and earthworm by HPLC-ID-MS/MS. d18-HBCDs used as internal standards were added to the samples before extraction. HBCDs enantiomers were extracted from soil by accelerated solvent extraction ( ASE ) with n-hexane/DCM (1:1,V/V) at 100℃ and 10 MPa for 5 min, and further cleaned up using silica column. HBCDs enantiomers were extracted from earthworm by vortex turbulence with ethyl acetate. The extracts were orderly sulphonated by sulfuric acid, and purified by silica column. For all HBCDs enantiomers, good linearities were obtained in the concentration range of 0. 25-50 ng/mL. Limits of detection ( LOD) and limits of quantification ( LOQ) were 0. 00544-0. 00766 ng/g and 0. 0173-0. 0244 ng/g, respectively in soil. The recoveries of spiked samples at 0. 05 and 2. 5 ng/g levels were 80. 0%-95. 9% with relative standard deviations ( RSD, %) of 5. 7%-11. 9% in soil. Limits of detection (LOD) and limits of quantification (LOQ) were 0. 0103-0. 0148 ng/g and 0. 0328-0. 0471 ng/g, respectively in earthworm. The recoveries of spiked samples at 0. 1 and 5 ng/g levels were 78. 0% -94. 4% with relative standard deviations ( RSD, %) of 6. 1% -12. 2% in earthworm. This method can meet the requirements of determination of trace HBCDs in soil and earthworm.
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OBJECTIVE:To develop a method for the separation of naproxen enantiomers. METHODS:The supercritical fluid chromatography(SFC)method was adopted. The chiral column,type and proportion of polar additive in mobile phase,back pres-sure and column temperature were optimized using the separation time,capacity factor,separation factor and separation degree as index. RESULTS:The best condition was on the chiral column CHIRALPAK?AD-H,with polar additive of isopropanol (20%), back pressure of 170 bar,column temperature of 20℃and the detection wavelength of 283 nm. Under this condition,baseline sep-aration of naproxen enantiomers can be achieved;separation degree was 4.31 and separation factor was 1.90;RSD of precision,sta-bility and reproducibility tests were no more than 2.65%(n=5). CONCLUSIONS:Established method is simple,reproducible and well-separated,and can be used for chiral separation of naproxen enantiomers.
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OBJECTIVE:To discuss the correlation between Interntion Normalized Ratio(INR)with concentration of warfarin enantiomer and dose density after cardiac valve replacement. METHODS:The plasma concentration of R-warfarin or S-warfarin, dose of unit weight and INR of 176 patients with anticoagulation after cardiac valve replacement in each time point were moni-tored,and the correlation of INR and warfarin plasma concentration or dose was observed. RESULTS:Doses of all patients in 24-288 h were significantly higher than 0 h,the differences were statistically significant(P0.05). Average plasma concentration of R-warfarin or S-warfarin had consistent trend,plasma concentration of enantiomers was fluctuated within a certain range after 108 h,there were no significant differences(P>0.05). Compared with 0 h,there was no significant difference when INR was 12 h (P>0.05),it increased significantly in 36 h and had been increasing,then fluctuated within a certain range after 108 h,compared with 108 h,there were no significant differences(P>0.05). The correlation coefficient between INR and unit weight dose of warfa-rin in 60 h>36 h>12 h,it showed correlation(P<0.001). There was certain correlation between plasma concentration of warfarin and dose density in 12,36 and 60 h. CONCLUSIONS:The correlation between plasma concentration of warfarin and unit weight dose is stronger than the correlation between INR and unit weight dose. When combined with other coagulation,it may help to man-age warfarin dose.
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Objective:To establish a method for the determination of enantiomer in rivaroxaban by HPLC. Methods:A Chiralpak IA column (250 mm × 4. 6 mm, 5 μm) was used with the mobile phase of 100% methanol. The flow rate was 1. 0 ml·min-1 . The detection wavelength was set at 250 nm and the column temperature was 40℃. Results:The resolution of rivaroxaban and the enanti-omer was above 2. 0. The linear range of them was 0. 5-1 000. 00 μg·ml-1(r=0. 999 9). The detection limit of the enantiomer was 0. 17ng and the average recovery was 102. 9% with RSD of 1. 54%(n=6). Conclusion:The method is accurate and rapid, and suit-able for the determination of the enantiomer in rivaroxaban.
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OBJECTIVE: To develop a chiral HPLC method for the determination of enantiomers of tirofiban hydrochloride.
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Aim To analyze the blocking effect of ( ± ) doxazosin [ ( ± ) DOX ] , ( -) doxazosin [ ( -) DOX] and ( +) doxazosin [( +) DOX] on the vaso-constriction of rat isolated mesenteric arterioles media-ted by α1-adrenoceptors. Methods The vasoconstric-tion induced by phenylephrine ( Phe) in the rat isola-ted mesenteric arterioles ( the second- and third-order branches) was recorded using DMT wire myograph sys-tem 620M, and theα1-adrenoceptor antagonistic activ-ity of ( ± ) DOX and its enantiomers was analyzed. Results The inner diameter of second- and third-or-der branches of the rat mesenteric artery was (162. 5 ± 5. 3) μm (n=11) and (103. 1 ± 2. 3) μm (n=23), respectively. The values of normalized preload of the second-and third-order branches, which were calculat-ed by the LabChart software, were (2. 93 ± 0. 51) mN ( n =11 ) and ( 2. 64 ± 0. 50 ) mN ( n =23 ) ( P >0. 05 ) . Vasoconstrictive responses to Phe in the sec-ond-order branche of rat mesenteric artery under nor-malized preloads were not significantly different from those under 5 mN preload;however, the Emax values of the Phe-induced vasoconstriction under 10 mN, 15 mN and 20 mN preloads were decreased by 12%, 29%and 43% ( P<0. 01 ) respectively compared with those under normalized preload. The concentration-response curves for Phe were shifted to right in a concentration dependent manner by ( -) DOX or ( +) DOX at 0. 001 , 0. 01 and 0. 1 μmol · L-1 without significant change in their Emax values in the second-and third-or-der branches of rat mesenteric artery. Schild plot anal-ysis indicated that ( -) DOX, ( +) DOX and ( ± ) DOX non-competitively inhibited the vasoconstrictive responses to Phe in the second-order branches, and the rank order of pKB values was ( +) DOX ( 8. 67 ± 0. 10 ) , ( ± ) DOX ( 8. 53 ± 0. 090 ) , ( -) DOX (7. 85 ± 0. 09). However, schild plot analysis indica-ted that ( -) DOX and ( +) DOX competitively inhibi-ted the vasoconstrictive responses for Phe in the third-order branch, and the rank order of their pKB values was ( ± ) DOX ( 8. 68 ± 0. 17 ) , ( +) DOX ( 8. 48 ± 0. 10 ) , ( -) DOX ( 7. 48 ± 0. 140 ) . Conclusion The α1-adrenoceptor blocking activity of ( -) DOX is much weaker than that of ( +) DOX or ( ± ) DOX in the rat isolated mesenteric arterioles, and there is a tendency to enhance the activity of ( ± ) DOX in third-order branches of the rat mesenteric artery though theα1-adrenoceptor blockade effect of ( ± ) DOX is not significantly different from ( +) DOX.